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A Phase 1b Open Label, Dose Escalation Study of PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma

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ClinicalTrials.gov Identifier: NCT01826448
Recruitment Status : Terminated (No activity was observed. BRAFi-naïve participants should have received triple combination treatment (including MEK inhibitor). Continuation was not justified.)
First Posted : April 8, 2013
Results First Posted : May 28, 2020
Last Update Posted : May 28, 2020
Sponsor:
Collaborator:
Plexxikon
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions V600-mutated BRAF Unresectable Melanoma
V600-mutated BRAF Metastatic Melanoma
Stage III or Stage IV Metastatic Melanoma That Has Not Been Previously Treated With a Selective BRAF Inhibitor
Interventions Drug: PLX3397
Drug: vemurafenib
Enrollment 13
Recruitment Details A total of 13 participants who met all inclusion and none of the exclusion criteria were enrolled in the study.
Pre-assignment Details This was an open-label, multicenter, Phase 1b, dose-escalation study, followed by an Extension Phase at the recommended Phase 2 dose (RP2D) of both drugs. During Dose-escalation (planned n=40), cohorts of 3 to 6 participants were enrolled to identify the RP2D of each agent to be administered to patients enrolled in the subsequent Extension Phase.
Arm/Group Title Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID
Hide Arm/Group Description Participant who received 800 mg/day (400 twice daily [BID]) of PLX3397 and 720 mg BID of vemurafenib. Participants who received 800 mg/day (400 twice daily [BID]) of PLX3397 and 960 mg BID of vemurafenib.
Period Title: Overall Study
Started 4 9
Completed 0 0
Not Completed 4 9
Reason Not Completed
Adverse Event             1             3
Disease progression             2             4
Withdrawal by Subject             1             0
Physician Decision             0             1
2 active cancers             0             1
Arm/Group Title Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID Total
Hide Arm/Group Description Participant who received 800 mg/day (400 twice daily [BID]) of PLX3397 and 720 mg BID of vemurafenib. Participants who received 800 mg/day (400 twice daily [BID]) of PLX3397 and 960 mg BID of vemurafenib. Total of all reporting groups
Overall Number of Baseline Participants 4 9 13
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 4 participants 9 participants 13 participants
42
(35 to 52)
60.1
(44 to 71)
54.5
(35 to 71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 9 participants 13 participants
Female
1
  25.0%
4
  44.4%
5
  38.5%
Male
3
  75.0%
5
  55.6%
8
  61.5%
1.Primary Outcome
Title Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma
Hide Description [Not Specified]
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Adverse events (AEs) were assessed in the modified intent-to-treat population (mITT).
Arm/Group Title Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID
Hide Arm/Group Description:
Participant who received 800 mg/day (400 twice daily [BID]) of PLX3397 and 720 mg BID of vemurafenib.
Participants who received 800 mg/day (400 twice daily [BID]) of PLX3397 and 960 mg BID of vemurafenib.
Overall Number of Participants Analyzed 4 9
Measure Type: Number
Unit of Measure: percentage of participants
Any primary system organ class 100 100
Any AE 100 100
AEs related to both PLX3397 and vemurafenib 100 55.6
AEs related to PLX3397 75 77.8
AEs related vemurafenib 25 77.8
AEs leading to withdrawal from any study treatment 25 44.4
AEs considered as dose limiting toxicities 25 33.3
Serious adverse events 0 44.4
Serious adverse events related to study treatment 0 22.2
Adverse events leading to death 0 0
Time Frame Adverse events (and serious AEs [SAEs]) were recorded from the time the participant received the first dose of study drug up to 28 days after the last dose, up to 1 year (mITT population).
Adverse Event Reporting Description Other non-serious adverse events occurring in ≥ 9 participants by system organ class or ≥ 3 participants by preferred term are reported from the mITT population.
 
Arm/Group Title Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID
Hide Arm/Group Description Participant who received 800 mg/day (400 twice daily [BID] of PLX3397 and 720 mg BID of vemurafenib. Participants who received 800 mg/day (400 twice daily [BID]) of PLX3397 and 960 mg BID of vemurafenib.
All-Cause Mortality
Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   0/9 (0.00%) 
Hide Serious Adverse Events
Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   4/9 (44.44%) 
Gastrointestinal disorders     
Gastrointestinal haemorrhage  1  0/4 (0.00%)  1/9 (11.11%) 
General disorders     
Pyrexia  1  0/4 (0.00%)  1/9 (11.11%) 
Infections and infestations     
Cellulitis  1  0/4 (0.00%)  1/9 (11.11%) 
Investigations     
Alanine aminotransferase increased  1  0/4 (0.00%)  2/9 (22.22%) 
Neutrophil count decreased  1  0/4 (0.00%)  1/9 (11.11%) 
Blood alkaline phosphatase increased  1  0/4 (0.00%)  1/9 (11.11%) 
Aspartate aminotransferase increased  1  0/4 (0.00%)  2/9 (22.22%) 
Nervous system disorders     
Cerebellar haemorrhage  1  0/4 (0.00%)  1/9 (11.11%) 
1
Term from vocabulary, MedDRA (10.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1; PLX3397 800 mg/Day + Vemurafenib 720 mg BID Cohort 2; PLX3397 800 mg/Day + Vemurafenib 960 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   4/4 (100.00%)   9/9 (100.00%) 
Blood and lymphatic system disorders     
Anaemia  1  1/4 (25.00%)  4/9 (44.44%) 
Gastrointestinal disorders     
Constipation  1  0/4 (0.00%)  3/9 (33.33%) 
Diarrhoea  1  1/4 (25.00%)  4/9 (44.44%) 
Gastrooesophageal reflux disease  1  0/4 (0.00%)  3/9 (33.33%) 
Nausea  1  1/4 (25.00%)  3/9 (33.33%) 
Vomiting  1  2/4 (50.00%)  3/9 (33.33%) 
General disorders     
Fatigue  1  1/4 (25.00%)  7/9 (77.78%) 
Pyrexia  1  0/4 (0.00%)  4/9 (44.44%) 
Investigations     
Alanine aminotransferase increased  1  1/4 (25.00%)  2/9 (22.22%) 
Aspartate aminotransferase increased  1  2/4 (50.00%)  5/9 (55.56%) 
Blood alkaline phosphatase increased  1  1/4 (25.00%)  4/9 (44.44%) 
Blood bilirubin increased  1  0/4 (0.00%)  3/9 (33.33%) 
Blood creatinine increased  1  1/4 (25.00%)  2/9 (22.22%) 
Lymphocyte count decreased  1  2/4 (50.00%)  1/9 (11.11%) 
Weight decreased  1  2/4 (50.00%)  1/9 (11.11%) 
Metabolism and nutrition disorders     
Decreased appetite  1  2/4 (50.00%)  3/9 (33.33%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/4 (25.00%)  4/9 (44.44%) 
Skin and subcutaneous tissue disorders     
Photosensitivity reaction  1  1/4 (25.00%)  2/9 (22.22%) 
Pruritus  1  1/4 (25.00%)  3/9 (33.33%) 
1
Term from vocabulary, MedDRA (10.1)
Indicates events were collected by systematic assessment
This study was terminated due to business decision before the planned sample size was reached; therefore, the planned outcome measure cannot be evaluated.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Daiichi Sankyo Inc.
Phone: 908-992-6400
EMail: CTRinfo@dsi.com
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT01826448    
Other Study ID Numbers: PLX108-09
First Submitted: April 1, 2013
First Posted: April 8, 2013
Results First Submitted: May 12, 2020
Results First Posted: May 28, 2020
Last Update Posted: May 28, 2020