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
- Some people have cancers that don't respond to standard treatments. In these cases, doctors may try to use drugs to slow the growth of the cancer.
- To test the safety and efficacy of the drug combination of ganetespib and ziv-aflibercept.
- Adults age 18 and over with advanced cancer of the colon, lung, urinary tract, and sarcomas.
- Participants will be screened with medical history, blood tests, and scans to measure their tumors.
- Participants will have one or two eye exams, with dilating eye drops.
- Participants will get the study drugs at the clinic as an infusion in a vein. Ganetespib will be given once a week on the same day for 3 weeks in a row, followed by a 1-week rest period. Ziv-aflibercept will be given once every other week. The drugs will be given in 28-day cycles.
- Participants may have a small piece of their tumor collected once or twice. This is done using a small needle during computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound scan.
- Participants will have their blood pressure checked at each visit. They will check it at home every day of the study.
- Participants may have one or more whole-body positron emission tomography (PET) scans with 89Zr-panitumumab. A small amount of a radioactive chemical will be injected through a tube in an arm. Participants will lie on a bed that slides in and out of the donut-shaped PET scanner. They will have small amounts of blood drawn.
- Participants may stay in the study as long as they are tolerating the drugs and their tumor is not getting worse.
|Condition or disease||Intervention/treatment||Phase|
|Neoplasms||Drug: Ziv-Aflibercept Drug: Ganetespib||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Ganetespib and Ziv-Aflibercept in Patients With Advanced Gastrointestinal Carcinomas, Non-Squamous Non-Small Cell Lung Carcinomas, Urothelial Carcinomas, and Sarcomas|
|Actual Study Start Date :||December 2, 2014|
|Actual Primary Completion Date :||February 25, 2016|
|Actual Study Completion Date :||February 25, 2016|
Experimental: Ganetespib and Ziv-Aflibercept
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 + ziv-aflibercept at 3 mg/kg or 4 mg/kg.
Ziv-aflibercept is a soluble fusion protein with high binding affinity for vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor B (VEGF-B), and placenta growth factor (PIGF) and thus confers anti-angiogenic activity
Ganetespib is a non-geldamycin synthetic inhibitor of Hsp90 with activity against multiple cancer cell lines and tumor xenografts in preclinical models.
Other Name: STA-9090
- 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 [ Time Frame: Date treatment consent signed to date off study, approximately 12 months and 44 days ]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.
- Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs [ Time Frame: Date treatment consent signed to date off study, approximately 12 months and 44 days ]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.
- Maximum Tolerated Dose (MTD) of the Combination of Ganetespib and Ziv-aflibercept [ Time Frame: Cycle one (28 days) ]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.
- Modulation of Hypoxia-Inducible Factor 1 (HIF-1) Alpha [ Time Frame: Cycle 2, Day 7 ]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.
- Modulation of Epidermal Growth Factor Receptor (EGFR) Expression [ Time Frame: Cycle 1 Day 16 ]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.
- Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) [ Time Frame: Baseline and every 2 months up to 5 months ]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.
- Number of Cycles on Treatment [ Time Frame: up to 5 months ]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.
- Number of Participants Who Had a Dose Limiting Toxicity (DLT) [ Time Frame: 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,...).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02192541
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Alice P Chen, M.D.||National Cancer Institute (NCI)|