Trial Outcomes & Findings for Ganetespib and Ziv-Aflibercept in Refractory Gastrointestinal Carcinomas, Non-Squamous Non-Small Cell Lung Carcinomas, Urothelial Carcinomas, and Sarcomas (NCT NCT02192541)
NCT ID: NCT02192541
Last Updated: 2018-03-29
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
5 participants
Primary outcome timeframe
Date treatment consent signed to date off study, approximately 12 months and 44 days
Results posted on
2018-03-29
Participant Flow
The escalation of dose was not performed as planned for this study due to toxicity and early termination of the trial.
Participant milestones
| Measure |
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 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 4 mg/kg.
|
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 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 Study
STARTED
|
2
|
3
|
|
Overall Study
Treated
|
2
|
3
|
|
Overall Study
Evaluable for Response
|
1
|
3
|
|
Overall Study
COMPLETED
|
2
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Ganetespib and Ziv-Aflibercept in Refractory Gastrointestinal Carcinomas, Non-Squamous Non-Small Cell Lung Carcinomas, Urothelial Carcinomas, and Sarcomas
Baseline characteristics by cohort
| Measure |
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg
n=2 Participants
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.
|
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
n=3 Participants
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
n=5 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
59 years
n=5 Participants
|
60 years
n=7 Participants
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Diagnosis
Colon adenocarcinomas
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Diagnosis
Small bowel adenocarcinomas
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Diagnosis
Rectal adenocarcinomas
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0: Fully active
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1: Restricted in physically strenuous activity
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
2: Unable to carry out any work activities
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
3: Capable of only limited self-care
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
4: Completely disabled
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
5: Dead
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Number of Prior Therapies
|
6.5 prior therapies
n=5 Participants
|
8 prior therapies
n=7 Participants
|
8 prior therapies
n=5 Participants
|
PRIMARY outcome
Timeframe: Date treatment consent signed to date off study, approximately 12 months and 44 daysHere 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.
Outcome measures
| Measure |
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg
n=2 Participants
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.
|
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
n=3 Participants
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.
|
|---|---|---|
|
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
|
2 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Date treatment consent signed to date off study, approximately 12 months and 44 daysAdverse 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.
Outcome measures
| Measure |
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg
n=2 Participants
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.
|
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
n=3 Participants
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.
|
|---|---|---|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 3 Abdominal Pain
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 2 Alanine Aminotransferase Increased
|
0 Participants
|
1 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 2 Hypocalcemia
|
0 Participants
|
1 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 2 Infusion Related Reaction
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 2 Lymphocycte Count Decreased
|
0 Participants
|
1 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 3 Alkaline Phosphtase Increased
|
0 Participants
|
1 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 3 Gastritis*
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 2 Anorexia
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 2 Diarrhea
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 2 EKG QT Corrected Interval Prolonged
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 2 Fatigue
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 2 Hypertension*
|
0 Participants
|
1 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 5 Small Intestinal Perforation*
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs
Grade 5 Sudden Death Not Otherwise Specified*
|
0 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Cycle one (28 days)Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycle 2, Day 7Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycle 1 Day 16Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and every 2 months up to 5 monthsRadiologic 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.
Outcome measures
| Measure |
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg
n=1 Participants
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.
|
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
n=3 Participants
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.
|
|---|---|---|
|
Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)
Complete Response
|
0 Participants
|
0 Participants
|
|
Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)
Partial Response
|
0 Participants
|
0 Participants
|
|
Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)
Stable Disease
|
0 Participants
|
3 Participants
|
|
Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)
Progressive Disease
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to 5 monthsPopulation: The number of participants who were evaluable for response
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.
Outcome measures
| Measure |
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg
n=1 Participants
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.
|
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
n=3 Participants
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.
|
|---|---|---|
|
Number of Cycles on Treatment
|
1 cycles
Interval 1.0 to 1.0
|
4 cycles
Interval 4.0 to 5.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Cycle one (28 days)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,...).
Outcome measures
| Measure |
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg
n=2 Participants
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.
|
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
n=3 Participants
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.
|
|---|---|---|
|
Number of Participants Who Had a Dose Limiting Toxicity (DLT)
|
0 Participants
|
0 Participants
|
Adverse Events
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg
Serious events: 1 serious events
Other events: 2 other events
Deaths: 1 deaths
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg
n=2 participants at risk
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.
|
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
n=3 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Rectal perforation
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Gastrointestinal disorders
Small intestinal perforation
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
General disorders
Sudden death Not Otherwise Specified
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
Other adverse events
| Measure |
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg
n=2 participants at risk
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.
|
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
n=3 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Investigations
Activated partial thromboplastin time prolonged
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
66.7%
2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Investigations
Aspartate aminotransferase increased
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
66.7%
2/3 • Number of events 3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
50.0%
1/2 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Eye disorders
Blurred vision
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Injury, poisoning and procedural complications
Bruising
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Investigations
Creatinine increased
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
66.7%
2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Cardiac disorders
Electrocardiogram QT corrected interval prolonged
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Infections and infestations
Eye infection
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
General disorders
Fatigue
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Gastrointestinal disorders
Gastritis
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
66.7%
2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Gastrointestinal disorders
Hemorrhoidal hemorrhage
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Vascular disorders
Hypertension
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
General disorders
Infusion related reaction
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Gastrointestinal disorders
Nausea
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
66.7%
2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Investigations
Platelet count decreased
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
66.7%
2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Investigations
Serum amylase increased
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Infections and infestations
Urinary tract infection
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Investigations
Weight loss
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
|
Musculoskeletal and connective tissue disorders
Shoulder pain
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 12 months and 44 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place