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Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01777776
Recruitment Status : Terminated (Study was withdrawn due to scientific and business considerations.)
First Posted : January 29, 2013
Results First Posted : September 13, 2016
Last Update Posted : September 13, 2016
Sponsor:
Information provided by (Responsible Party):
Array BioPharma

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Locally Advanced Metastatic BRAF Mutant Melanoma
Interventions Drug: LEE011
Drug: LGX818
Enrollment 28
Recruitment Details

Recruitment to CLEE011X2105 began on 10-July-2013. The study concluded on 13-April-2015. Participant Flow data is comprised of the Full Analysis Set (FAS), which is all patients who received at least one dose of LGX818 or LEE011.

Not completed subjects represents subjects that stopped treatment early, due to the corresponding reason.

Pre-assignment Details In response to developments in the treatment of melanoma, the sponsor reviewed the data from the ongoing study and decided to halt further enrollment of patients in the Phase Ib part of the study. Consequently, the Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns.
Arm/Group Title Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort)
Hide Arm/Group Description

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Period Title: Overall Study
Started 6 12 6 4
Completed 0 0 0 0
Not Completed 6 12 6 4
Reason Not Completed
Adverse Event             2             4             0             0
Disease Progression             4             8             6             3
Withdrawal by Subject             0             0             0             1
Arm/Group Title Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) Total
Hide Arm/Group Description

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Total of all reporting groups
Overall Number of Baseline Participants 6 12 6 4 28
Hide Baseline Analysis Population Description
Baseline data is comprised of the Full Analysis Set (FAS), which is all patients who received at least one dose of LGX818 or LEE011.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 12 participants 6 participants 4 participants 28 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
2
  33.3%
10
  83.3%
4
  66.7%
2
  50.0%
18
  64.3%
>=65 years
4
  66.7%
2
  16.7%
2
  33.3%
2
  50.0%
10
  35.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 12 participants 6 participants 4 participants 28 participants
65.0  (10.71) 49.8  (13.66) 58.0  (10.55) 62.0  (17.63) 56.6  (13.90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 12 participants 6 participants 4 participants 28 participants
Female
3
  50.0%
7
  58.3%
1
  16.7%
0
   0.0%
11
  39.3%
Male
3
  50.0%
5
  41.7%
5
  83.3%
4
 100.0%
17
  60.7%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 6 participants 12 participants 6 participants 4 participants 28 participants
84.60  (12.793) 78.08  (17.069) 80.17  (10.308) 74.70  (16.415) 79.44  (14.450)
WHO/ECOG performance status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 12 participants 6 participants 4 participants 28 participants
0 2 4 1 1 8
1 4 7 5 3 19
2 0 1 0 0 1
[1]
Measure Description:

Categories:

  • 0 - Fully active, able to carry on all pre-disease performance without restriction
  • 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
  • 2 - Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
  • 3 - Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
  • 4 - Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
1.Primary Outcome
Title Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
Hide Description

Dose Limiting Toxicities (DLTs) during the first 28 days of the combination treatment of LEE011 and LGX818.

Due to the halt of enrollment, no Maximum Tolerated Dose (MTD) was formally declared during the study.

Time Frame Cycle 1 (approximately 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis group is comprised of the Safety Set (SS), which includes all patients who received at least one dose of LEE011 or LGX818, and have at least one valid post-baseline safety assessment.
Arm/Group Title Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort)
Hide Arm/Group Description:

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Overall Number of Participants Analyzed 6 12 6 4
Measure Type: Number
Unit of Measure: participants with DLTs
Myalagia 1 0 0 0
Elevated Bilirubin 1 0 0 0
Neuralgia 0 0 1 0
Maculopapular Rash 0 0 0 1
2.Primary Outcome
Title Phase II - Progression Free Survival (PFS)
Hide Description

As per RECIST v1.1, PFS is the time from date of randomization/ start of treatment to the date of event defined as the first documented progression or death due to any cause.

Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed.

Time Frame Approximately 23 months after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.
Arm/Group Title Phase II - Arm 1a (LGX818+LEE011) Phase II - Arm 1b (LGX818)
Hide Arm/Group Description:

Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Primary Outcome
Title Phase II - Objective Response Rate (ORR)
Hide Description

As per RECIST v1.1, ORR is defined as the proportion of patients with a best overall response of complete response or partial response.

Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed.

Time Frame Approximately 23 months after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.
Arm/Group Title Phase II - Arm 2 (BRAFi Resistant)
Hide Arm/Group Description:
Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Phase I - Number of Subjects Experiencing at Least One Adverse Event (AE).
Hide Description [Not Specified]
Time Frame Approximately 23 months after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis group is comprised of the Safety Set (SS), which includes all patients who received at least one dose of LEE011 or LGX818, and have at least one valid post-baseline safety assessment.
Arm/Group Title Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort)
Hide Arm/Group Description:

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Overall Number of Participants Analyzed 6 12 6 4
Measure Type: Number
Unit of Measure: participants
6 12 6 4
5.Secondary Outcome
Title Phase I - Number of Subjects Experiencing at Least One Serious Adverse Event (SAE).
Hide Description [Not Specified]
Time Frame Approximately 23 months after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis group is comprised of the Safety Set (SS), which is all patients who received at least one dose of LEE011 or LGX818, and have at least one valid post-baseline safety assessment.
Arm/Group Title Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort)
Hide Arm/Group Description:

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Overall Number of Participants Analyzed 6 12 6 4
Measure Type: Number
Unit of Measure: participants
3 5 3 1
6.Secondary Outcome
Title Phase Ib/II - Plasma Concentration-time Profiles
Hide Description Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to plasma concentration time profiles were not performed.
Time Frame 28-day cycles
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.
Arm/Group Title Phase I (Dose Escalation) Phase II - Arm 1a (LGX818+LEE011) Phase II - Arm 1b (LGX818) Phase II - Arm 2 (BRAFi Resistant)
Hide Arm/Group Description:

Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Phase Ib/II - Overall Response Rate (ORR)
Hide Description

ORR is defined as the proportion of patients with a best overall response of complete response or partial response.

Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.

Time Frame Approximately 23 months after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.
Arm/Group Title Phase I (Dose Escalation) Phase II - Arm 1a (LGX818+LEE011) Phase II - Arm 1b (LGX818)
Hide Arm/Group Description:

Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Phase Ib/II - Progression Free Survival (PFS)
Hide Description

PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause.

Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.

Time Frame Approximately 23 months after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.
Arm/Group Title Phase I (Dose Escalation) Phase II - Arm 2 (BRAFi Resistant)
Hide Arm/Group Description:

Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Phase Ib/II - Duration Of Response (DOR)
Hide Description

DOR is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer.

Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.

Time Frame Approximately 23 months after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.
Arm/Group Title Phase I (Dose Escalation) Phase II - Arm 1a (LGX818+LEE011) Phase II - Arm 1b (LGX818) Phase II - Arm 2 (BRAFi Resistant)
Hide Arm/Group Description:

Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Phase II - Overall Survival (OS)
Hide Description

OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive.

Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.

Time Frame Approximately 23 months after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib.
Arm/Group Title Phase II - Arm 1a (LGX818+LEE011) Phase II - Arm 1b (LGX818) Phase II - Arm 2 (BRAFi Resistant)
Hide Arm/Group Description:

Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Phase Ib/II - Pharmacokinetic Parameters: AUCtau
Hide Description Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
Time Frame 28-day cycles
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.
Arm/Group Title Phase I (Dose Escalation) Phase II - Arm 1a (LGX818+LEE011) Phase II - Arm 1b (LGX818) Phase II - Arm 2 (BRAFi Resistant)
Hide Arm/Group Description:

Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Phase Ib/II - Pharmacokinetic Parameters: Cmin
Hide Description Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
Time Frame 28-day cycles
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.
Arm/Group Title Phase I (Dose Escalation) Phase II - Arm 1a (LGX818+LEE011) Phase II - Arm 1b (LGX818) Phase II - Arm 2 (BRAFi Resistant)
Hide Arm/Group Description:

Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Phase Ib/II - Pharmacokinetic Parameters: Cmax
Hide Description Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
Time Frame 28-day cycles
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.
Arm/Group Title Phase I (Dose Escalation) Phase II - Arm 1a (LGX818+LEE011) Phase II - Arm 1b (LGX818) Phase II - Arm 2 (BRAFi Resistant)
Hide Arm/Group Description:

Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title Phase Ib/II - Pharmacokinetic Parameters: Tmax
Hide Description Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
Time Frame 28-day cycles
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.
Arm/Group Title Phase I (Dose Escalation) Phase II - Arm 1a (LGX818+LEE011) Phase II - Arm 1b (LGX818) Phase II - Arm 2 (BRAFi Resistant)
Hide Arm/Group Description:

Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Phase Ib/II - Pharmacokinetic Parameters: Racc
Hide Description Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
Time Frame 28-day cycles
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data.
Arm/Group Title Phase I (Dose Escalation) Phase II - Arm 1a (LGX818+LEE011) Phase II - Arm 1b (LGX818) Phase II - Arm 2 (BRAFi Resistant)
Hide Arm/Group Description:

Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle).

Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years.
Adverse Event Reporting Description An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
 
Arm/Group Title Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort)
Hide Arm/Group Description

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment.

Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment.

All-Cause Mortality
Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/6 (50.00%)      5/12 (41.67%)      3/6 (50.00%)      1/4 (25.00%)    
Gastrointestinal disorders         
Nausea * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Hepatobiliary disorders         
Transaminases increased * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Immune system disorders         
Systemic inflammatory response syndrome * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Infections and infestations         
Pneumonia * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Sepsis * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Injury, poisoning and procedural complications         
Brain oedema * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 1/4 (25.00%)  1
Musculoskeletal and connective tissue disorders         
Chest wall abscess * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Failure to thrive * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Neck pain * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Nervous system disorders         
Memory impairment * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Seizure * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Simple partial seizures * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Spinal cord compression * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Psychiatric disorders         
Confusional state * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Mental status changes * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Renal and urinary disorders         
Urinary tract infection * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Skin and subcutaneous tissue disorders         
Dermatitis bullous * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Vascular disorders         
Syncope * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      12/12 (100.00%)      6/6 (100.00%)      4/4 (100.00%)    
Blood and lymphatic system disorders         
Anaemia * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 2/6 (33.33%)  2 1/4 (25.00%)  1
Lymphopenia * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 2/4 (50.00%)  2
Neutropenia * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Thrombocytopenia * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Disseminated intravascular coagulation * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Increased tendency to bruise * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Leukopenia * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Lymphadenopathy * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Cardiac disorders         
Tachycardia * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 2/4 (50.00%)  2
Palpitations * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Ear and labyrinth disorders         
Ear pruritus * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Endocrine disorders         
Adrenal insufficiency * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Cushingoid * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Eye disorders         
Eye pruritus * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Vision blurred * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Blepharospasm * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Dry eye * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Eye discharge * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Photophobia * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Gastrointestinal disorders         
Nausea * 1  2/6 (33.33%)  2 6/12 (50.00%)  6 4/6 (66.67%)  4 4/4 (100.00%)  4
Vomiting * 1  1/6 (16.67%)  1 3/12 (25.00%)  3 3/6 (50.00%)  3 2/4 (50.00%)  2
Constipation * 1  3/6 (50.00%)  3 3/12 (25.00%)  3 1/6 (16.67%)  1 0/4 (0.00%)  0
Diarrhoea * 1  2/6 (33.33%)  2 2/12 (16.67%)  2 1/6 (16.67%)  1 2/4 (50.00%)  2
Stomatitis * 1  1/6 (16.67%)  1 4/12 (33.33%)  4 1/6 (16.67%)  1 0/4 (0.00%)  0
Abdominal distension * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 1/6 (16.67%)  1 0/4 (0.00%)  0
Abdominal pain * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 1/4 (25.00%)  1
Dyspepsia * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Oral pain * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0
Abdominal discomfort * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Abdominal pain upper * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Cheilitis * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Dysphagia * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Gingival discolouration * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Gingival ulceration * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Glossitis * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Glossodynia * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Haemorrhoidal haemorrhage * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Haemorrhoids * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Retching * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
General disorders         
Fatigue * 1  2/6 (33.33%)  2 6/12 (50.00%)  6 4/6 (66.67%)  4 3/4 (75.00%)  3
Oedema peripheral * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 2/6 (33.33%)  2 0/4 (0.00%)  0
Chills * 1  1/6 (16.67%)  1 2/12 (16.67%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0
Pyrexia * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 1/6 (16.67%)  1 0/4 (0.00%)  0
Localised oedema * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Non-cardiac chest pain * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Peripheral swelling * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Xerosis * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Infections and infestations         
Oral candidiasis * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0
Skin candida * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Cellulitis * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Conjunctivitis * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Dermatitis infected * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 1/4 (25.00%)  1
Fungal infection * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Furuncle * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Lower respiratory tract infection * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Skin abrasion * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Injury, poisoning and procedural complications         
Fall * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Arthropod bite * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Laceration * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Muscle strain * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Post procedural complication * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Post procedural discharge * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Sunburn * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Investigations         
Blood creatinine increased * 1  4/6 (66.67%)  4 1/12 (8.33%)  1 1/6 (16.67%)  1 1/4 (25.00%)  1
Electrocardiogram QT prolonged * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 2/6 (33.33%)  2 0/4 (0.00%)  0
Weight decreased * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 1/4 (25.00%)  1
Alanine aminotransferase increased * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Aspartate aminotransferase increased * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Blood sodium decreased * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 1/4 (25.00%)  1
White blood cell count decreased * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0
Blood alkaline phosphatase increased * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Blood bilirubin increased * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Blood glucose increased * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Blood iron decreased * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Blood phosphorus decreased * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Blood potassium decreased * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Blood thyroid stimulating hormone increased * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Cardiac murmur * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Lymphocyte count decreased * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Neutrophil count decreased * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Troponin increased * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Metabolism and nutrition disorders         
Hypoalbuminaemia * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 3/6 (50.00%)  3 1/4 (25.00%)  1
Decreased appetite * 1  1/6 (16.67%)  1 2/12 (16.67%)  2 0/6 (0.00%)  0 1/4 (25.00%)  1
Hypophosphataemia * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 1/6 (16.67%)  1 1/4 (25.00%)  1
Hypokalaemia * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Dehydration * 1  2/6 (33.33%)  2 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Hyperglycaemia * 1  2/6 (33.33%)  2 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Hypermagnesaemia * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Hyponatraemia * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Hyperkalaemia * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Hypocalcaemia * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Myalgia * 1  2/6 (33.33%)  2 4/12 (33.33%)  4 1/6 (16.67%)  1 0/4 (0.00%)  0
Arthralgia * 1  1/6 (16.67%)  1 3/12 (25.00%)  3 1/6 (16.67%)  1 1/4 (25.00%)  1
Pain in extremity * 1  1/6 (16.67%)  1 3/12 (25.00%)  3 2/6 (33.33%)  2 0/4 (0.00%)  0
Neck pain * 1  1/6 (16.67%)  1 2/12 (16.67%)  2 0/6 (0.00%)  0 1/4 (25.00%)  1
Musculoskeletal pain * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 1/6 (16.67%)  1 1/4 (25.00%)  1
Back pain * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Muscle spasms * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Musculoskeletal chest pain * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0
Musculoskeletal stiffness * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Flank pain * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Groin pain * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Joint swelling * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Muscular weakness * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Osteoporosis * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Periarthritis * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Acrochordon * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0
Melanocytic naevus * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Skin papilloma * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Squamous cell carcinoma of skin * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Acanthoma * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Infected neoplasm * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Neoplasm * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Seborrhoeic keratosis * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Nervous system disorders         
Headache * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 1/6 (16.67%)  1 1/4 (25.00%)  1
Dysgeusia * 1  2/6 (33.33%)  2 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Dizziness * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0
Neuralgia * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Peripheral sensory neuropathy * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Somnolence * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 2/6 (33.33%)  2 0/4 (0.00%)  0
Balance disorder * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Hyperaesthesia * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Hypoaesthesia * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Neuropathy peripheral * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Paraesthesia * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Partial seizures * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Peripheral motor neuropathy * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Sciatica * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Syncope * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 1/4 (25.00%)  1
Psychiatric disorders         
Insomnia * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 1/4 (25.00%)  1
Mood swings * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Anger * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Confusional state * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Irritability * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Mental status changes * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Sleep disorder * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Renal and urinary disorders         
Acute kidney injury * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Dysuria * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Renal impairment * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Urinary retention * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Reproductive system and breast disorders         
Penile oedema * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Scrotal oedema * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Scrotal pain * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Scrotal swelling * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Oropharyngeal pain * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 1/6 (16.67%)  1 0/4 (0.00%)  0
Cough * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Dyspnoea * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Pulmonary embolism * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Rhinorrhoea * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Dry throat * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Dysphonia * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Dyspnoea exertional * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Pleural effusion * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Upper-airway cough syndrome * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Wheezing * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Skin and subcutaneous tissue disorders         
Palmar-plantar erythrodysaesthesia syndrome * 1  2/6 (33.33%)  2 7/12 (58.33%)  7 3/6 (50.00%)  3 1/4 (25.00%)  1
Pruritus * 1  2/6 (33.33%)  2 7/12 (58.33%)  7 1/6 (16.67%)  1 2/4 (50.00%)  2
Alopecia * 1  3/6 (50.00%)  3 2/12 (16.67%)  2 1/6 (16.67%)  1 1/4 (25.00%)  1
Dry skin * 1  1/6 (16.67%)  1 4/12 (33.33%)  4 2/6 (33.33%)  2 0/4 (0.00%)  0
Rash * 1  4/6 (66.67%)  4 2/12 (16.67%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0
Rash maculo-papular * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 2/4 (50.00%)  2
Hyperkeratosis * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 2/4 (50.00%)  2
Dermatitis acneiform * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 1/4 (25.00%)  1
Erythema * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Hyperhidrosis * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0
Night sweats * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0
Palmoplantar keratoderma * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Photosensitivity reaction * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0
Pruritus generalised * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 1/4 (25.00%)  1
Skin exfoliation * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Skin hyperpigmentation * 1  1/6 (16.67%)  1 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Skin sensitisation * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Transient acantholytic dermatosis * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0
Actinic keratosis * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Cold sweat * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Ephelides * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Intertrigo * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Leukoplakia * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Pain of skin * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Psoriasis * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Rash erythematous * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Rash papular * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0
Rash pruritic * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Skin hypopigmentation * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
Skin lesion * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Vitiligo * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Vascular disorders         
Flushing * 1  3/6 (50.00%)  3 1/12 (8.33%)  1 0/6 (0.00%)  0 1/4 (25.00%)  1
Hot flush * 1  0/6 (0.00%)  0 2/12 (16.67%)  2 0/6 (0.00%)  0 1/4 (25.00%)  1
Hypotension * 1  0/6 (0.00%)  0 0/12 (0.00%)  0 0/6 (0.00%)  0 2/4 (50.00%)  2
Embolism * 1  0/6 (0.00%)  0 1/12 (8.33%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0
Hypertension * 1  1/6 (16.67%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Study recruitment was halted on 07-Aug-2014 during the Phase Ib part of the study. The Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of the sponsor's agreements with its investigators may vary. However, the sponsor does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Array BioPharma, Inc.
Phone: 303-381-6604
EMail: info@arraybiopharma.com
Layout table for additonal information
Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT01777776    
Other Study ID Numbers: CLEE011X2105
First Submitted: January 22, 2013
First Posted: January 29, 2013
Results First Submitted: April 13, 2016
Results First Posted: September 13, 2016
Last Update Posted: September 13, 2016