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Phase Ib and Phase II Studies of MK-3475 in Combination + for Renal Cell Carcinoma:

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: NCT02348008
Recruitment Status : Completed
First Posted : January 28, 2015
Results First Posted : July 31, 2020
Last Update Posted : July 31, 2020
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Big Ten Cancer Research Consortium
Information provided by (Responsible Party):
Arkadiusz Z. Dudek, MD, Big Ten Cancer Research Consortium

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Clear Cell Renal Carcinoma
Interventions Drug: MK-3475
Drug: Bevacizumab
Enrollment 61
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm A - Phase 1b Dose Escalation Cohort Arm A - Phase Ib Dose Ecalation Cohort 2 Arm B - Phase II Investigational Treatment
Hide Arm/Group Description

Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.

MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV

Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV;

Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.

MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV

Bevacizumab: Arm A: Phase 1b Cohort 2: 15mg IV

The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.

MK-3475: Arm B: Phase II Treatment: 200mg IV

Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.

Period Title: Overall Study
Started 3 10 48
Completed 0 0 29
Not Completed 3 10 19
Reason Not Completed
Adverse Event             2             3             3
Disease Progression             1             5             16
Withdrawal by Subject             0             1             0
Symptomatic Deterioration             0             1             0
Arm/Group Title Arm A - Phase 1b Dose Escalation Cohort Arm B - Phase II Investigational Treatment Total
Hide Arm/Group Description

Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.

MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV

Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV

The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.

MK-3475: Arm B: Phase II Treatment: 200mg IV

Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.

Total of all reporting groups
Overall Number of Baseline Participants 13 48 61
Hide Baseline Analysis Population Description
No per-group analysis was completed in the dose escalation cohort because the Phase IB dose-finding study found no dose-limiting toxicities and the primary objective (determine MTD) was satisfied. The baseline demographics as presented have been presented in several abstracts and published in the Journal of Clinical Oncology.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 13 participants 48 participants 61 participants
55
(33 to 68)
61
(42 to 84)
60
(33 to 84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 48 participants 61 participants
Female
2
  15.4%
15
  31.3%
17
  27.9%
Male
11
  84.6%
33
  68.8%
44
  72.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 48 participants 61 participants
Hispanic or Latino
0
   0.0%
5
  10.4%
5
   8.2%
Not Hispanic or Latino
10
  76.9%
38
  79.2%
48
  78.7%
Unknown or Not Reported
3
  23.1%
5
  10.4%
8
  13.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 48 participants 61 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
10
  76.9%
45
  93.8%
55
  90.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
  23.1%
3
   6.3%
6
   9.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants 48 participants 61 participants
13 48 61
Karnofsky Performance Status (KPS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 48 participants 61 participants
KPS 70
2
  15.4%
3
   6.3%
5
   8.2%
KPS 80
3
  23.1%
10
  20.8%
13
  21.3%
KPS 90
1
   7.7%
20
  41.7%
21
  34.4%
KPS 100
7
  53.8%
15
  31.3%
22
  36.1%
[1]
Measure Description:

KPS is a general indicator of a subject's well being and ability to carry on daily activities.

100:Normal no complaints 90:Able to carry on normal activity 80:Normal activity with effort; some signs or symptoms of disease. 70:Cares for self 60:Requires occasional assistance, but is able to care for most of his personal needs. 50:Requires considerable assistance and frequent medical care.

40:Disabled 30:Severely disabled 20:Very sick 10:Moribund 0:Dead

Prior Nephrectomy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 48 participants 61 participants
Yes
11
  84.6%
43
  89.6%
54
  88.5%
No
2
  15.4%
5
  10.4%
7
  11.5%
Bone Metastases  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 48 participants 61 participants
Yes
6
  46.2%
10
  20.8%
16
  26.2%
No
7
  53.8%
38
  79.2%
45
  73.8%
Metastatic RCC Prognosis (by IMDC/Heng Score)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 48 participants 61 participants
Favorable
5
  38.5%
10
  20.8%
15
  24.6%
Intermediate
3
  23.1%
31
  64.6%
34
  55.7%
Poor
5
  38.5%
7
  14.6%
12
  19.7%
[1]
Measure Description:

The IMDC\Heng Score is calculated based on the number of risk factors:

0 Risk Factors: Favorable Prognosis 1-2 Risk Factors: Intermediate Prognosis 3-6 Risk Factors: Poor Prognosis

1.Primary Outcome
Title Phase 1b: Maximum Safe Dose of Treatment Regimen
Hide Description To establish the maximum tested safe dose of bevacizumab in combination with 200mg of MK-3475(pembrolizumab) for subjects with metastatic clear cell renal carcinoma after failure of at least one systemic therapy for metastatic disease.
Time Frame Every 21 days while on treatment (estimated 4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A - Phase 1b Dose Escalation Cohort
Hide Arm/Group Description:

Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.

MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV

Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV

Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: mg/kg
15
2.Primary Outcome
Title Overall Response Rate
Hide Description

To determine the activity of combination of MK-3475 and bevacizumab in first line therapy for subjects with treatment naïve metastatic clear cell RCC as assessed by response rates (complete or partial response) By calculating the proportion of subjects with a response (CR, PR) based on RECIST 1.1 where:

Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

Time Frame Every 6 weeks while on treatment (estimated 10 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Results for Arm A - Phase Ib are reported as a single group, no per-group analyses were planned or performed.
Arm/Group Title Arm A - Phase 1b Dose Escalation Cohort Arm B - Phase II Investigational Treatment
Hide Arm/Group Description:

Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.

MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV

Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV

The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.

MK-3475: Arm B: Phase II Treatment: 200mg IV

Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.

Overall Number of Participants Analyzed 13 48
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
41.7
(15.2 to 72.3)
60.9
(45.4 to 74.9)
3.Secondary Outcome
Title Progression-Free Survival
Hide Description

To determine median progression-free survival (PFS) for this patient population, per RECIST 1.1 where:

Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

Time Frame Up to two years from enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
Results for Arm A - Phase Ib are reported as a single group, no per-group analyses were planned or performed.
Arm/Group Title Arm A - Phase 1b Dose Escalation Cohort Arm B - Phase II Investigational Treatment
Hide Arm/Group Description:

Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.

MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV

Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV

The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.

MK-3475: Arm B: Phase II Treatment: 200mg IV

Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.

Overall Number of Participants Analyzed 13 47
Median (95% Confidence Interval)
Unit of Measure: months
9.9
(4.9 to 16.7)
20.7
(11.3 to 27.4)
4.Secondary Outcome
Title Overall Survival
Hide Description To determine if treatment regimen improves overall survival for this patient population. Median overall survival will be calculated up to 2 years from registration.
Time Frame Up to 2 years from registration
Hide Outcome Measure Data
Hide Analysis Population Description
Results for Arm A - Phase Ib are reported as a single group, no per-group analyses were planned or performed.
Arm/Group Title Arm A - Phase 1b Dose Escalation Cohort Arm B - Phase II Investigational Treatment
Hide Arm/Group Description:

Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.

MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV

Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV

The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.

MK-3475: Arm B: Phase II Treatment: 200mg IV

Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.

Overall Number of Participants Analyzed 13 47
Median (95% Confidence Interval)
Unit of Measure: Months
17.9 [1] 
(6.3 to NA)
NA [2] 
(NA to NA)
[1]
95% confidence interval upper limit not estimable
[2]
Median OS was not reached (only 15 of 47 evaluable subjects died)
5.Secondary Outcome
Title Clinical Benefit Rate
Hide Description

To determine the proportion of subjects with clinical benefit (complete response, partial response, or stable disease) based on RECIST 1.1, where:

Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

Time Frame Every 6 months while on treatment (estimated 4-10 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Results for Arm A - Phase Ib are reported as a single group, no per-group analyses were planned or performed.
Arm/Group Title Arm A - Phase 1b Dose Escalation Cohort Arm B - Phase II Investigational Treatment
Hide Arm/Group Description:

Cohort 1 will consist of 3-6 patients who will receive MK-3475 200mg and bevacizumab 10mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

Cohort 2 will consist of 3-9 patients who will receive MK-3475 200mg and bevacizumab 15mg on day 1 of the 21-day cycle. The drugs are administered 15-30 minutes apart in separate intravenous infusions.

If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional 3 subjects will be enrolled at dose level 2. If all three subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.

MK-3475: Arm A: Phase 1b Cohort 1: 200mg IV; Arm A: Phase 1b Cohort 2: 200mg IV

Bevacizumab: Arm A: Phase 1b Cohort 1: 10mg IV; Arm A: Phase 1b Cohort 2: 15mg IV

The maximum safe dose of MK-3475 in combination bevacizumab (as determined in the phase 1b cohort) will be given on day 1 of each 21 day cycle.

MK-3475: Arm B: Phase II Treatment: 200mg IV

Bevacizumab: Arm B: Phase II Treatment: administered at the maximum safe dose of 5mg or 10mg as established in the Phase 1b dose escalation cohort study.

Overall Number of Participants Analyzed 13 46
Measure Type: Number
Unit of Measure: percentage of subjects
91.67 100
6.Secondary Outcome
Title Characterize Adverse Events
Hide Description Characterize adverse effects (AE) of pembrolizumab in combination with bevacizumab in subjects with metastatic RCC after failure of at least one systemic therapy. Toxicity will be assessed using CTCAE version 4. All grade 3 and 4 treatment-related adverse events will be reported.
Time Frame Every week while on treatment (estimated 4-10 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population for this objective was defined in the protocol as "all subjects who received at least one dose of study drug". No per-arm or per-cohort analyses were planned or performed.
Arm/Group Title All Subjects
Hide Arm/Group Description:
Adverse events are summarized for all study participants who received at least one dose of study drug.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: events
Duodenal ulcer: Grade 4 1
Hyponatremia: Grade 4 1
Hypertension: Grade 3 15
Proteinuria: Grade 3 6
Adrenal insufficiency: Grade 3 4
Pain/Headaches: Grade 3 3
Pneumonitis: Grade 3 2
Hyponatremia: Grade 3 2
Generalized muscle weakness: Grade 3 2
Dehydration: Grade 3 2
Skin Rashes: Grade 3 2
Anemia: Grade 3 2
Nausea: Grade 3 1
Vomiting: Grade 3 1
Thromboembolic event: Grade 3 1
Seizure: Grade 3 1
Myocardial infarction: Grade 3 1
Mucositis oral: Grade 3 1
Immune mediated hepatitis: Grade 3 1
Immune mediated gastritis: Grade 3 1
Hypothyroidism 1
Hematuria 1
Flu like symptoms: Grade 3 1
Diarrhea: Grade 3 1
Arthralgia: Grade 3 1
Alkaline phosphatase increased: Grade 3 1
Time Frame Every week while on treatment (estimated 4-10 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Subjects
Hide Arm/Group Description Adverse events are summarized for all study participants who received at least one dose of study drug. Per the protocol, the safety analysis population "will comprise all subjects who received at least one dose of study drug". Consequently, no per-group analyses were planned or performed.
All-Cause Mortality
All Subjects
Affected / at Risk (%)
Total   28/61 (45.90%)    
Hide Serious Adverse Events
All Subjects
Affected / at Risk (%) # Events
Total   32/61 (52.46%)    
Blood and lymphatic system disorders   
ANEMIA * 1  1/61 (1.64%)  1
Cardiac disorders   
ACUTE CORONARY SYNDROME * 1  1/61 (1.64%)  1
CARDIAC DISORDERS * 1  1/61 (1.64%)  1
HEART FAILURE * 1  1/61 (1.64%)  1
MYOCARDIAL INFARCTION * 1  1/61 (1.64%)  1
Endocrine disorders   
ADRENAL INSUFFICIENCY * 1  5/61 (8.20%)  5
HYPOTHYROIDISM * 1  1/61 (1.64%)  1
Gastrointestinal disorders   
COLITIS * 1  1/61 (1.64%)  1
DUODENAL ULCER * 1  1/61 (1.64%)  1
GASTROINTESTINAL DISORDERS * 1  2/61 (3.28%)  2
PANCREATITIS * 1  1/61 (1.64%)  1
General disorders   
NON-CARDIAC CHEST PAIN * 1  1/61 (1.64%)  1
PAIN * 1  2/61 (3.28%)  2
Infections and infestations   
ABDOMINAL INFECTION * 1  1/61 (1.64%)  1
INFECTIONS AND INFESTATIONS * 1  1/61 (1.64%)  1
SMALL INTESTINE INFECTION * 1  1/61 (1.64%)  1
SOFT TISSUE INFECTION * 1  1/61 (1.64%)  1
UPPER RESPIRATORY INFECTION * 1  1/61 (1.64%)  1
URINARY TRACT INFECTION * 1  1/61 (1.64%)  1
Metabolism and nutrition disorders   
ANOREXIA * 1  1/61 (1.64%)  1
HYPERCALCEMIA * 1  2/61 (3.28%)  2
HYPERGLYCEMIA * 1  1/61 (1.64%)  1
Musculoskeletal and connective tissue disorders   
ARTHRALGIA * 1  1/61 (1.64%)  1
BACK PAIN * 1  1/61 (1.64%)  1
BUTTOCK PAIN * 1  1/61 (1.64%)  1
CHEST WALL PAIN * 1  1/61 (1.64%)  1
GENERALIZED MUSCLE WEAKNESS * 1  1/61 (1.64%)  1
MUSCLE WEAKNESS LOWER LIMB * 1  1/61 (1.64%)  1
Nervous system disorders   
HEADACHE * 1  1/61 (1.64%)  1
SEIZURE * 1  1/61 (1.64%)  2
STROKE * 1  1/61 (1.64%)  1
SYNCOPE * 1  1/61 (1.64%)  1
TRANSIENT ISCHEMIC ATTACKS * 1  1/61 (1.64%)  1
Renal and urinary disorders   
ACUTE KIDNEY INJURY * 1  2/61 (3.28%)  2
HEMATURIA * 1  1/61 (1.64%)  2
PROTEINURIA * 1  1/61 (1.64%)  1
Reproductive system and breast disorders   
PELVIC PAIN * 1  1/61 (1.64%)  1
Respiratory, thoracic and mediastinal disorders   
DYSPNEA * 1  2/61 (3.28%)  2
PLEURAL EFFUSION * 1  1/61 (1.64%)  1
PNEUMONITIS * 1  3/61 (4.92%)  3
Vascular disorders   
HYPOTENSION * 1  1/61 (1.64%)  1
THROMBOEMBOLIC EVENT * 1  1/61 (1.64%)  1
VASCULAR DISORDERS * 1  1/61 (1.64%)  1
1
Term from vocabulary, CTCAEv4
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
All Subjects
Affected / at Risk (%) # Events
Total   60/61 (98.36%)    
Blood and lymphatic system disorders   
ANEMIA * 1  12/61 (19.67%)  18
BLOOD AND LYMPHATIC SYSTEM DISORDERS * 1  2/61 (3.28%)  3
LEUKOCYTOSIS * 1  3/61 (4.92%)  4
Cardiac disorders   
ATRIAL FIBRILLATION * 1  2/61 (3.28%)  2
CARDIAC DISORDERS * 1  4/61 (6.56%)  4
CHEST PAIN - CARDIAC * 1  1/61 (1.64%)  1
LEFT VENTRICULAR SYSTOLIC DYSFUNCTION * 1  1/61 (1.64%)  1
PALPITATIONS * 1  1/61 (1.64%)  1
SINUS BRADYCARDIA * 1  4/61 (6.56%)  4
SINUS TACHYCARDIA * 1  2/61 (3.28%)  2
SUPRAVENTRICULAR TACHYCARDIA * 1  1/61 (1.64%)  1
Ear and labyrinth disorders   
EAR AND LABYRINTH DISORDERS * 1  1/61 (1.64%)  1
EAR PAIN * 1  1/61 (1.64%)  1
VERTIGO * 1  1/61 (1.64%)  1
Endocrine disorders   
ADRENAL INSUFFICIENCY * 1  3/61 (4.92%)  5
ENDOCRINE DISORDERS * 1  1/61 (1.64%)  1
HYPERPARATHYROIDISM * 1  1/61 (1.64%)  1
HYPERTHYROIDISM * 1  3/61 (4.92%)  3
HYPOTHYROIDISM * 1  14/61 (22.95%)  16
Eye disorders   
BLURRED VISION * 1  3/61 (4.92%)  3
DRY EYE * 1  2/61 (3.28%)  3
EYE DISORDERS * 1  4/61 (6.56%)  6
EYE PAIN * 1  2/61 (3.28%)  2
WATERING EYES * 1  3/61 (4.92%)  3
Gastrointestinal disorders   
ABDOMINAL DISTENSION * 1  1/61 (1.64%)  1
ABDOMINAL PAIN * 1  10/61 (16.39%)  15
ANAL HEMORRHAGE * 1  1/61 (1.64%)  1
BLOATING * 1  2/61 (3.28%)  2
COLITIS * 1  2/61 (3.28%)  4
CONSTIPATION * 1  25/61 (40.98%)  34
DENTAL CARIES * 1  2/61 (3.28%)  2
DIARRHEA * 1  25/61 (40.98%)  40
DRY MOUTH * 1  4/61 (6.56%)  4
DYSPEPSIA * 1  5/61 (8.20%)  5
DYSPHAGIA * 1  4/61 (6.56%)  4
FLATULENCE * 1  3/61 (4.92%)  3
GASTRIC ULCER * 1  3/61 (4.92%)  3
GASTRITIS * 1  4/61 (6.56%)  5
GASTROESOPHAGEAL REFLUX DISEASE * 1  8/61 (13.11%)  9
GASTROINTESTINAL DISORDERS * 1  13/61 (21.31%)  18
HEMORRHOIDAL HEMORRHAGE * 1  2/61 (3.28%)  2
HEMORRHOIDS * 1  3/61 (4.92%)  3
LOWER GASTROINTESTINAL HEMORRHAGE * 1  1/61 (1.64%)  1
MUCOSITIS ORAL * 1  9/61 (14.75%)  14
NAUSEA * 1  27/61 (44.26%)  38
ORAL DYSESTHESIA * 1  4/61 (6.56%)  4
ORAL PAIN * 1  2/61 (3.28%)  2
PANCREATITIS * 1  2/61 (3.28%)  2
RECTAL HEMORRHAGE * 1  1/61 (1.64%)  1
STOMACH PAIN * 1  3/61 (4.92%)  3
TOOTHACHE * 1  2/61 (3.28%)  2
VOMITING * 1  15/61 (24.59%)  27
General disorders   
CHILLS * 1  5/61 (8.20%)  5
EDEMA FACE * 1  1/61 (1.64%)  1
EDEMA LIMBS * 1  19/61 (31.15%)  24
FATIGUE * 1  44/61 (72.13%)  66
FEVER * 1  3/61 (4.92%)  3
FLU LIKE SYMPTOMS * 1  3/61 (4.92%)  4
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS * 1  8/61 (13.11%)  15
IRRITABILITY * 1  1/61 (1.64%)  1
LOCALIZED EDEMA * 1  3/61 (4.92%)  3
NECK EDEMA * 1  1/61 (1.64%)  1
NON-CARDIAC CHEST PAIN * 1  2/61 (3.28%)  2
PAIN * 1  12/61 (19.67%)  14
Hepatobiliary disorders   
CHOLECYSTITIS * 1  1/61 (1.64%)  1
HEPATOBILIARY DISORDERS * 1  2/61 (3.28%)  2
Immune system disorders   
ALLERGIC REACTION * 1  2/61 (3.28%)  2
Infections and infestations   
BRONCHIAL INFECTION * 1  1/61 (1.64%)  1
INFECTIONS AND INFESTATIONS * 1  4/61 (6.56%)  4
LIP INFECTION * 1  1/61 (1.64%)  1
LUNG INFECTION * 1  1/61 (1.64%)  1
NAIL INFECTION * 1  1/61 (1.64%)  1
PAPULOPUSTULAR RASH * 1  1/61 (1.64%)  1
RHINITIS INFECTIVE * 1  1/61 (1.64%)  2
SINUSITIS * 1  7/61 (11.48%)  12
SKIN INFECTION * 1  3/61 (4.92%)  3
SOFT TISSUE INFECTION * 1  1/61 (1.64%)  2
TOOTH INFECTION * 1  3/61 (4.92%)  5
UPPER RESPIRATORY INFECTION * 1  15/61 (24.59%)  22
URINARY TRACT INFECTION * 1  8/61 (13.11%)  9
Injury, poisoning and procedural complications   
BRUISING * 1  4/61 (6.56%)  4
BURN * 1  2/61 (3.28%)  2
FALL * 1  5/61 (8.20%)  5
FRACTURE * 1  1/61 (1.64%)  1
INJURY, POISONING AND PROCEDURAL COMPLICATIONS * 1  3/61 (4.92%)  3
Investigations   
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED * 1  5/61 (8.20%)  6
ALANINE AMINOTRANSFERASE INCREASED * 1  9/61 (14.75%)  15
ALKALINE PHOSPHATASE INCREASED * 1  11/61 (18.03%)  16
ASPARTATE AMINOTRANSFERASE INCREASED * 1  12/61 (19.67%)  17
BLOOD BILIRUBIN INCREASED * 1  5/61 (8.20%)  8
CHOLESTEROL HIGH * 1  5/61 (8.20%)  5
CREATININE INCREASED * 1  21/61 (34.43%)  38
HEMOGLOBIN INCREASED * 1  2/61 (3.28%)  5
INR INCREASED * 1  2/61 (3.28%)  2
INVESTIGATIONS * 1  10/61 (16.39%)  20
LIPASE INCREASED * 1  1/61 (1.64%)  1
LYMPHOCYTE COUNT DECREASED * 1  2/61 (3.28%)  2
NEUTROPHIL COUNT DECREASED * 1  1/61 (1.64%)  1
PLATELET COUNT DECREASED * 1  6/61 (9.84%)  9
SERUM AMYLASE INCREASED * 1  1/61 (1.64%)  1
WEIGHT GAIN * 1  8/61 (13.11%)  9
WEIGHT LOSS * 1  18/61 (29.51%)  19
Metabolism and nutrition disorders   
ANOREXIA * 1  25/61 (40.98%)  35
DEHYDRATION * 1  6/61 (9.84%)  9
HYPERCALCEMIA * 1  10/61 (16.39%)  13
HYPERGLYCEMIA * 1  11/61 (18.03%)  22
HYPERKALEMIA * 1  15/61 (24.59%)  19
HYPERNATREMIA * 1  3/61 (4.92%)  3
HYPOALBUMINEMIA * 1  8/61 (13.11%)  10
HYPOCALCEMIA * 1  4/61 (6.56%)  4
HYPOGLYCEMIA * 1  4/61 (6.56%)  4
HYPOKALEMIA * 1  1/61 (1.64%)  1
HYPOMAGNESEMIA * 1  2/61 (3.28%)  2
HYPONATREMIA * 1  11/61 (18.03%)  27
METABOLISM AND NUTRITION DISORDERS * 1  2/61 (3.28%)  2
Musculoskeletal and connective tissue disorders   
ARTHRALGIA * 1  7/61 (11.48%)  10
ARTHRITIS * 1  10/61 (16.39%)  10
BACK PAIN * 1  16/61 (26.23%)  21
BONE PAIN * 1  5/61 (8.20%)  5
BUTTOCK PAIN * 1  2/61 (3.28%)  2
FLANK PAIN * 1  3/61 (4.92%)  4
GENERALIZED MUSCLE WEAKNESS * 1  5/61 (8.20%)  5
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER * 1  22/61 (36.07%)  29
MYALGIA * 1  7/61 (11.48%)  8
NECK PAIN * 1  2/61 (3.28%)  2
OSTEONECROSIS OF JAW * 1  1/61 (1.64%)  2
PAIN IN EXTREMITY * 1  16/61 (26.23%)  28
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) * 1  2/61 (3.28%)  2
Nervous system disorders   
ATAXIA * 1  1/61 (1.64%)  1
COGNITIVE DISTURBANCE * 1  1/61 (1.64%)  1
DIZZINESS * 1  12/61 (19.67%)  15
DYSGEUSIA * 1  7/61 (11.48%)  7
HEADACHE * 1  25/61 (40.98%)  34
MEMORY IMPAIRMENT * 1  1/61 (1.64%)  1
NERVOUS SYSTEM DISORDERS * 1  5/61 (8.20%)  5
PARESTHESIA * 1  1/61 (1.64%)  1
PERIPHERAL SENSORY NEUROPATHY * 1  2/61 (3.28%)  2
SEIZURE * 1  2/61 (3.28%)  3
SINUS PAIN * 1  1/61 (1.64%)  1
TREMOR * 1  2/61 (3.28%)  2
Psychiatric disorders   
ANXIETY * 1  6/61 (9.84%)  7
DEPRESSION * 1  6/61 (9.84%)  7
INSOMNIA * 1  12/61 (19.67%)  14
PSYCHIATRIC DISORDERS * 1  1/61 (1.64%)  1
Renal and urinary disorders   
ACUTE KIDNEY INJURY * 1  3/61 (4.92%)  3
HEMATURIA * 1  9/61 (14.75%)  13
PROTEINURIA * 1  24/61 (39.34%)  62
RENAL AND URINARY DISORDERS * 1  10/61 (16.39%)  15
URINARY FREQUENCY * 1  2/61 (3.28%)  3
URINARY INCONTINENCE * 1  1/61 (1.64%)  2
URINARY RETENTION * 1  3/61 (4.92%)  3
URINARY TRACT PAIN * 1  1/61 (1.64%)  1
URINARY URGENCY * 1  1/61 (1.64%)  1
Reproductive system and breast disorders   
BREAST PAIN * 1  1/61 (1.64%)  1
ERECTILE DYSFUNCTION * 1  1/61 (1.64%)  1
GENITAL EDEMA * 1  1/61 (1.64%)  1
REPRODUCTIVE SYSTEM AND BREAST DISORDERS * 1  2/61 (3.28%)  2
TESTICULAR DISORDER * 1  1/61 (1.64%)  1
TESTICULAR PAIN * 1  4/61 (6.56%)  4
Respiratory, thoracic and mediastinal disorders   
ADULT RESPIRATORY DISTRESS SYNDROME * 1  1/61 (1.64%)  1
ALLERGIC RHINITIS * 1  3/61 (4.92%)  3
COUGH * 1  25/61 (40.98%)  34
DYSPNEA * 1  12/61 (19.67%)  17
EPISTAXIS * 1  10/61 (16.39%)  14
HICCUPS * 1  1/61 (1.64%)  1
HOARSENESS * 1  8/61 (13.11%)  8
HYPOXIA * 1  3/61 (4.92%)  3
NASAL CONGESTION * 1  4/61 (6.56%)  4
PNEUMONITIS * 1  4/61 (6.56%)  5
POSTNASAL DRIP * 1  6/61 (9.84%)  8
PRODUCTIVE COUGH * 1  7/61 (11.48%)  8
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS * 1  13/61 (21.31%)  20
SLEEP APNEA * 1  1/61 (1.64%)  1
SNEEZING * 1  2/61 (3.28%)  2
SORE THROAT * 1  2/61 (3.28%)  2
VOICE ALTERATION * 1  4/61 (6.56%)  4
WHEEZING * 1  1/61 (1.64%)  2
Skin and subcutaneous tissue disorders   
ALOPECIA * 1  1/61 (1.64%)  1
DRY SKIN * 1  10/61 (16.39%)  12
ERYTHEMA MULTIFORME * 1  1/61 (1.64%)  1
HYPERHIDROSIS * 1  2/61 (3.28%)  2
NAIL RIDGING * 1  1/61 (1.64%)  1
PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME * 1  3/61 (4.92%)  3
PERIORBITAL EDEMA * 1  1/61 (1.64%)  1
PRURITUS * 1  20/61 (32.79%)  24
PURPURA * 1  1/61 (1.64%)  1
RASH ACNEIFORM * 1  1/61 (1.64%)  1
RASH MACULO-PAPULAR * 1  19/61 (31.15%)  27
SKIN AND SUBCUTANEOUS TISSUE DISORDERS * 1  22/61 (36.07%)  32
SKIN HYPERPIGMENTATION * 1  2/61 (3.28%)  2
SKIN ULCERATION * 1  1/61 (1.64%)  1
Social circumstances   
MENOPAUSE * 1  1/61 (1.64%)  1
Surgical and medical procedures   
SURGICAL AND MEDICAL PROCEDURES * 1  3/61 (4.92%)  4
Vascular disorders   
HOT FLASHES * 1  1/61 (1.64%)  1
HYPERTENSION * 1  39/61 (63.93%)  93
HYPOTENSION * 1  5/61 (8.20%)  5
LYMPHEDEMA * 1  1/61 (1.64%)  1
THROMBOEMBOLIC EVENT * 1  2/61 (3.28%)  3
VASCULAR DISORDERS * 1  1/61 (1.64%)  1
1
Term from vocabulary, CTCAEv4
*
Indicates events were collected by non-systematic assessment
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: Clinicaltrials.gov Results Coordinator
Organization: Hoosier Cancer Research Network
Phone: 317-921-2050
EMail: jsmith@hoosiercancer.org
Layout table for additonal information
Responsible Party: Arkadiusz Z. Dudek, MD, Big Ten Cancer Research Consortium
ClinicalTrials.gov Identifier: NCT02348008    
Other Study ID Numbers: BTCRC GU14-003
First Submitted: January 16, 2015
First Posted: January 28, 2015
Results First Submitted: February 6, 2020
Results First Posted: July 31, 2020
Last Update Posted: July 31, 2020