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Ganetespib and Ziv-Aflibercept in Refractory Gastrointestinal Carcinomas, Non-Squamous Non-Small Cell Lung Carcinomas, Urothelial Carcinomas, and Sarcomas

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ClinicalTrials.gov Identifier: NCT02192541
Recruitment Status : Terminated (Drug supplier suspended further clinical development of Ganetespib)
First Posted : July 17, 2014
Results First Posted : January 30, 2018
Last Update Posted : March 29, 2018
Sponsor:
Information provided by (Responsible Party):
Alice Chen, M.D., National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasms
Interventions Drug: Ziv-Aflibercept
Drug: Ganetespib
Enrollment 5
Recruitment Details  
Pre-assignment Details The escalation of dose was not performed as planned for this study due to toxicity and early termination of the trial.
Arm/Group Title Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Hide Arm/Group Description Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 4 mg/kg. Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was administered at a level of 100 mg/m^2 and ziv-aflibercept at 3 mg/kg.
Period Title: Overall Study
Started 2 3
Treated 2 3
Evaluable for Response 1 3
Completed 2 3
Not Completed 0 0
Arm/Group Title Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg Total
Hide Arm/Group Description Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 4 mg/kg. Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was administered at a level of 100 mg/m^2 and ziv-aflibercept at 3 mg/kg. Total of all reporting groups
Overall Number of Baseline Participants 2 3 5
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 3 participants 5 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
1
  50.0%
3
 100.0%
4
  80.0%
>=65 years
1
  50.0%
0
   0.0%
1
  20.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 2 participants 3 participants 5 participants
59
(51 to 67)
60
(50 to 63)
60
(50 to 67)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 3 participants 5 participants
Female
2
 100.0%
1
  33.3%
3
  60.0%
Male
0
   0.0%
2
  66.7%
2
  40.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 3 participants 5 participants
Hispanic or Latino
0
   0.0%
1
  33.3%
1
  20.0%
Not Hispanic or Latino
2
 100.0%
2
  66.7%
4
  80.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 3 participants 5 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
1
  50.0%
0
   0.0%
1
  20.0%
White
1
  50.0%
2
  66.7%
3
  60.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
  33.3%
1
  20.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 2 participants 3 participants 5 participants
2 3 5
Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 3 participants 5 participants
Colon adenocarcinomas
1
  50.0%
2
  66.7%
3
  60.0%
Small bowel adenocarcinomas
0
   0.0%
1
  33.3%
1
  20.0%
Rectal adenocarcinomas
1
  50.0%
0
   0.0%
1
  20.0%
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 3 participants 5 participants
0: Fully active
0
   0.0%
0
   0.0%
0
   0.0%
1: Restricted in physically strenuous activity
2
 100.0%
3
 100.0%
5
 100.0%
2: Unable to carry out any work activities
0
   0.0%
0
   0.0%
0
   0.0%
3: Capable of only limited self-care
0
   0.0%
0
   0.0%
0
   0.0%
4: Completely disabled
0
   0.0%
0
   0.0%
0
   0.0%
5: Dead
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: The Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status is graded on a scale of 0 to 5, with higher scores indicating lower levels of functioning in terms of ability to care for oneself, daily activities, and physical abilities (walking, working, etc.).
Number of Prior Therapies  
Median (Full Range)
Unit of measure:  Prior therapies
Number Analyzed 2 participants 3 participants 5 participants
6.5
(5 to 8)
8
(6 to 15)
8
(5 to 15)
1.Primary Outcome
Title Number of Participants With Serious and Non-serious Adverse Events Regardless of Attribution Assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v4.0
Hide Description Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame Date treatment consent signed to date off study, approximately 12 months and 44 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Hide Arm/Group Description:
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 4 mg/kg.
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was administered at a level of 100 mg/m^2 and ziv-aflibercept at 3 mg/kg.
Overall Number of Participants Analyzed 2 3
Measure Type: Count of Participants
Unit of Measure: Participants
2
 100.0%
3
 100.0%
2.Primary Outcome
Title Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Hide Description Adverse Events were graded according to Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. Grade refers to the severity of the Adverse Event. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event (AE). AEs were considered possibly attributable to both study drugs, except where otherwise noted. Star (*) symbol indicates that the AE is possibly related to Ziv-aflibercept and unlikely to be related to Ganetespib.
Time Frame Date treatment consent signed to date off study, approximately 12 months and 44 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Hide Arm/Group Description:
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 4 mg/kg.
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was administered at a level of 100 mg/m^2 and ziv-aflibercept at 3 mg/kg.
Overall Number of Participants Analyzed 2 3
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 2 Alanine Aminotransferase Increased
0
   0.0%
1
  33.3%
Grade 2 Anorexia
1
  50.0%
0
   0.0%
Grade 2 Diarrhea
1
  50.0%
0
   0.0%
Grade 2 EKG QT Corrected Interval Prolonged
1
  50.0%
0
   0.0%
Grade 2 Fatigue
1
  50.0%
0
   0.0%
Grade 2 Hypertension*
0
   0.0%
1
  33.3%
Grade 2 Hypocalcemia
0
   0.0%
1
  33.3%
Grade 2 Infusion Related Reaction
1
  50.0%
0
   0.0%
Grade 2 Lymphocycte Count Decreased
0
   0.0%
1
  33.3%
Grade 3 Abdominal Pain
1
  50.0%
0
   0.0%
Grade 3 Alkaline Phosphtase Increased
0
   0.0%
1
  33.3%
Grade 3 Gastritis*
1
  50.0%
0
   0.0%
Grade 5 Small Intestinal Perforation*
1
  50.0%
0
   0.0%
Grade 5 Sudden Death Not Otherwise Specified*
0
   0.0%
1
  33.3%
3.Primary Outcome
Title Maximum Tolerated Dose (MTD) of the Combination of Ganetespib and Ziv-aflibercept
Hide Description MTD is defined as the dose level at which no more than 1 of 6 patients experience a dose limiting toxicity (DLT) during the first cycle of the treatment, and the dose level below that at which at least 2 (of <6) patients have a DLT as a result of the drug. Determination of DLT is based on the first cycle of treatment.
Time Frame Cycle one (28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
An MTD was not established because no MTD data were collected. The trial was terminated before the MTD was reached due to the decision of the drug supplier to suspend further clinical development of ganetespib.
Arm/Group Title Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Hide Arm/Group Description:
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 4 mg/kg.
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 3 mg/kg.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Modulation of Hypoxia-Inducible Factor 1 (HIF-1) Alpha
Hide Description To determine whether the combination of ganetespib and ziv-aflibercept modulated intratumoral Hypoxia-inducible factor 1 (HIF-1)-alpha expression, tumor biopsies were to be analyzed for change in HIF-1-alpha expression by immunofluorescence assay (IFA). Paired pre-and post-combination treatment samples were to be compared for qualitative changes in levels of HIF-1- alpha expression. Cores were to be normalized against the percentage of tumor within the sample.
Time Frame Cycle 2, Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected from any participant. Biopsies were to be collected from an expansion cohort treated at the maximum tolerated dose, after the conclusion of the dose escalation phase. Trial was closed before the MTD was established, patients were not enrolled to an expansion phase, and samples for pharmacodynamics analysis were not obtained.
Arm/Group Title Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Hide Arm/Group Description:
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 4 mg/kg.
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 3 mg/kg.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Modulation of Epidermal Growth Factor Receptor (EGFR) Expression
Hide Description To evaluate for tumor distribution of EGFR, patients were to undergo 89Zr-immuno-positron emission tomography (PET) imaging with 89Zr-labeled EGFR-targeting panitumumab antibody evaluate modulation of EGFR client protein prior to and after treatment with the combination of ganetespib and ziv-aflibercept. Panitumumab is a fully human monoclonal antibody that targets EGFR and competes with endogenous ligands to block stimulation of EGFR. 89z-immuno-PET imaging with panitumumab as a targeting ligand allows for quantification of EGFR within tumors.
Time Frame Cycle 1 Day 16
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected from any participant for this Outcome Measure. As the trial was closed before the maximum tolerated dose (MTD) was established, patients were not enrolled to an expansion phase, and samples for pharmacodynamics analysis were not obtained.
Arm/Group Title Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Hide Arm/Group Description:
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 4 mg/kg.
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 3 mg/kg.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)
Hide Description Radiologic response assessments by computed tomography (CT) scans were performed at baseline and every two cycles to evaluate tumor response based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria for target lesions: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.
Time Frame Baseline and every 2 months up to 5 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Hide Arm/Group Description:
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 4 mg/kg.
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was administered at a level of 100 mg/m^2 and ziv-aflibercept at 3 mg/kg.
Overall Number of Participants Analyzed 1 3
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
0
   0.0%
Partial Response
0
   0.0%
0
   0.0%
Stable Disease
0
   0.0%
3
 100.0%
Progressive Disease
1
 100.0%
0
   0.0%
7.Secondary Outcome
Title Number of Cycles on Treatment
Hide Description The number of 28-day treatment cycles (ganetespib on days 1, 8, and 15; ziv-aflibercept on days 1 and 15) administered to each evaluable patient. Number represents treatment cycles that were started; not all cycles were completed.
Time Frame up to 5 months
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants who were evaluable for response
Arm/Group Title Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Hide Arm/Group Description:
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 4 mg/kg.
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was administered at a level of 100 mg/m^2 and ziv-aflibercept at 3 mg/kg.
Overall Number of Participants Analyzed 1 3
Median (Full Range)
Unit of Measure: cycles
1
(1 to 1)
4
(4 to 5)
8.Other Pre-specified Outcome
Title Number of Participants Who Had a Dose Limiting Toxicity (DLT)
Hide Description A DLT is defined as an adverse event that is related (possibly, probably, or definitely) to administration of study drugs during cycle one and is a Grade ≥ 3 non-hematological toxicity. Grade ≥3 non-hematological toxicity felt to be related to study medications are: Grade 3 diarrhea if it is refractory to treatment; Grade 3 nausea and vomiting if it is refractory to anti-emetic therapy and unable to be corrected; rise in creatinine to Grade 3, not corrected to Grade 1 or less within 48 hours with intravenous (IV) fluids; Any Grade 4 corrected QT interval (QTc) prolongation; Grade 4 neutropenia ≥5 days or febrile neutropenia,...).
Time Frame Cycle one (28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Hide Arm/Group Description:
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 4 mg/kg.
Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 3 mg/kg.
Overall Number of Participants Analyzed 2 3
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
Time Frame Date treatment consent signed to date off study, approximately 12 months and 44 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Hide Arm/Group Description Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was started at a dose level of 100 mg/m^2 and ziv-aflibercept at 4 mg/kg. Ganetespib was administered intravenously, over 1 hour, weekly, on days 1, 8, and 15 of each 28-day cycle. Ziv-aflibercept was administered intravenously, over 1 hour, every 2 weeks, on days 1 and 15 of each 28-day cycle. Ganetespib was administered at a level of 100 mg/m^2 and ziv-aflibercept at 3 mg/kg.
All-Cause Mortality
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   1/2 (50.00%)      2/3 (66.67%)    
Show Serious Adverse Events Hide Serious Adverse Events
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/2 (50.00%)      2/3 (66.67%)    
Gastrointestinal disorders     
Rectal perforation  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
Small intestinal perforation  1 [2]  1/2 (50.00%)  1 0/3 (0.00%)  0
General disorders     
Sudden death Not Otherwise Specified  1 [2]  0/2 (0.00%)  0 1/3 (33.33%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
Grade 5, Stent placement; surgical complications (unlikely related to study drugs)
[2]
Grade 5, possibly related to Ziv-Aflibercept
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/2 (100.00%)      3/3 (100.00%)    
Blood and lymphatic system disorders     
Anemia  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
Cardiac disorders     
Electrocardiogram QT corrected interval prolonged  1 [2]  1/2 (50.00%)  1 0/3 (0.00%)  0
Electrocardiogram QT corrected interval prolonged  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  2
Eye disorders     
Blurred vision  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
Gastrointestinal disorders     
Abdominal pain  1 [3]  1/2 (50.00%)  2 0/3 (0.00%)  0
Abdominal pain  1 [1]  1/2 (50.00%)  1 0/3 (0.00%)  0
Abdominal pain  1 [4]  0/2 (0.00%)  0 1/3 (33.33%)  1
Abdominal pain  1 [5]  0/2 (0.00%)  0 1/3 (33.33%)  1
Constipation  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
Constipation  1 [4]  0/2 (0.00%)  0 1/3 (33.33%)  1
Constipation  1 [6]  0/2 (0.00%)  0 1/3 (33.33%)  1
Diarrhea  1 [1]  1/2 (50.00%)  1 2/3 (66.67%)  8
Diarrhea  1 [2]  1/2 (50.00%)  1 0/3 (0.00%)  0
Gastritis  1 [7]  1/2 (50.00%)  1 0/3 (0.00%)  0
Gastrointestinal pain  1 [6]  0/2 (0.00%)  0 1/3 (33.33%)  1
Hemorrhoidal hemorrhage  1 [6]  0/2 (0.00%)  0 1/3 (33.33%)  1
Nausea  1 [1]  1/2 (50.00%)  1 2/3 (66.67%)  2
Oral pain  1 [6]  0/2 (0.00%)  0 1/3 (33.33%)  1
Rectal hemorrhage  1 [6]  1/2 (50.00%)  1 0/3 (0.00%)  0
Vomiting  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
General disorders     
Fatigue  1 [2]  1/2 (50.00%)  1 0/3 (0.00%)  0
Infusion related reaction  1 [2]  1/2 (50.00%)  1 0/3 (0.00%)  0
Infusion related reaction  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
Infections and infestations     
Eye infection  1 [4]  0/2 (0.00%)  0 1/3 (33.33%)  1
Urinary tract infection  1 [4]  1/2 (50.00%)  1 0/3 (0.00%)  0
Injury, poisoning and procedural complications     
Bruising  1 [6]  0/2 (0.00%)  0 1/3 (33.33%)  1
Investigations     
Activated partial thromboplastin time prolonged  1 [6]  0/2 (0.00%)  0 1/3 (33.33%)  2
Activated partial thromboplastin time prolonged  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
Alanine aminotransferase increased  1 [1]  1/2 (50.00%)  1 1/3 (33.33%)  1
Alanine aminotransferase increased  1 [2]  0/2 (0.00%)  0 1/3 (33.33%)  1
Alkaline phosphatase increased  1 [3]  0/2 (0.00%)  0 1/3 (33.33%)  1
Alkaline phosphatase increased  1 [4]  0/2 (0.00%)  0 1/3 (33.33%)  1
Aspartate aminotransferase increased  1 [1]  1/2 (50.00%)  1 2/3 (66.67%)  3
Creatinine increased  1 [5]  0/2 (0.00%)  0 2/3 (66.67%)  2
Lymphocyte count decreased  1 [2]  0/2 (0.00%)  0 1/3 (33.33%)  1
Lymphocyte count decreased  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  3
Platelet count decreased  1 [1]  0/2 (0.00%)  0 2/3 (66.67%)  2
Serum amylase increased  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
Weight loss  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
Weight loss  1 [6]  0/2 (0.00%)  0 1/3 (33.33%)  1
Metabolism and nutrition disorders     
Anorexia  1 [2]  1/2 (50.00%)  1 0/3 (0.00%)  0
Anorexia  1 [1]  0/2 (0.00%)  0 2/3 (66.67%)  2
Dehydration  1 [4]  1/2 (50.00%)  1 0/3 (0.00%)  0
Dehydration  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
Hypercalcemia  1 [6]  1/2 (50.00%)  1 0/3 (0.00%)  0
Hyperkalemia  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
Hyperuricemia  1 [6]  0/2 (0.00%)  0 1/3 (33.33%)  1
Hypoalbuminemia  1 [6]  1/2 (50.00%)  1 1/3 (33.33%)  3
Hypocalcemia  1 [2]  0/2 (0.00%)  0 1/3 (33.33%)  1
Hyponatremia  1 [1]  1/2 (50.00%)  1 1/3 (33.33%)  2
Hyponatremia  1 [6]  0/2 (0.00%)  0 1/3 (33.33%)  1
Hypophosphatemia  1 [4]  1/2 (50.00%)  1 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1 [6]  1/2 (50.00%)  2 0/3 (0.00%)  0
Shoulder pain  1 [4]  1/2 (50.00%)  1 0/3 (0.00%)  0
Nervous system disorders     
Dizziness  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  1
Renal and urinary disorders     
Hematuria  1 [5]  0/2 (0.00%)  0 2/3 (66.67%)  2
Proteinuria  1 [5]  0/2 (0.00%)  0 1/3 (33.33%)  1
Vascular disorders     
Hypertension  1 [4]  1/2 (50.00%)  1 1/3 (33.33%)  1
Hypertension  1 [6]  1/2 (50.00%)  1 0/3 (0.00%)  0
Hypertension  1 [1]  0/2 (0.00%)  0 1/3 (33.33%)  2
Hypertension  1 [5]  0/2 (0.00%)  0 1/3 (33.33%)  2
Hypertension  1 [8]  0/2 (0.00%)  0 1/3 (33.33%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
Grade 1, possibly related to study drugs
[2]
Grade 2, possibly related to study drugs
[3]
Grade 3, possibly related to study drugs
[4]
Grade 2, unlikely related to study drugs
[5]
Grade 1, possibly related to Ziv-Aflibercept
[6]
Grade 1, unlikely related to study drugs
[7]
Grade 3, possibly related to Ziv-Aflibercept
[8]
Grade 2, possibly related to Ziv-Aflibercept
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Alice P. Chen, M.D.
Organization: National Cancer Institute
Phone: (240) 781-3320
Responsible Party: Alice Chen, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT02192541     History of Changes
Other Study ID Numbers: 140150
14-C-0150
First Submitted: July 15, 2014
First Posted: July 17, 2014
Results First Submitted: October 30, 2017
Results First Posted: January 30, 2018
Last Update Posted: March 29, 2018