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NCT02192541

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

Terminated Phase 1 Results posted Last updated 29 March 2018
What this trial tests

Phase 1 trial testing Ziv-Aflibercept in Neoplasms in 5 participants. Terminated before completion.

Timeline
2 December 2014
Primary endpoint
25 February 2016
25 February 2016

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment5
Start date2 December 2014
Primary completion25 February 2016
Estimated completion25 February 2016
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 120, any sex, with Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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 o

GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg2
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg3
Number of Participants With Grade 2 or Greater Adverse Events Possibly, Probably, or Definitely Related to Administration of the Study Drugs Primary · 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

Grade 2 Alanine Aminotransferase Increased
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg0
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg1
Grade 2 Anorexia
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg1
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg0
Grade 2 Diarrhea
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg1
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg0
Grade 2 EKG QT Corrected Interval Prolonged
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg1
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg0
Grade 2 Fatigue
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg1
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg0
Grade 2 Hypertension*
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg0
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg1
Grade 2 Hypocalcemia
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg0
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg1
Grade 2 Infusion Related Reaction
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg1
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg0
Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) Secondary · 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 tar

Complete Response
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg0
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg0
Partial Response
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg0
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg0
Stable Disease
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg0
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg3
Progressive Disease
GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg1
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg0
Number of Cycles on Treatment Secondary · 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.

GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg11 – 1
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg44 – 5
Number of Participants Who Had a Dose Limiting Toxicity (DLT) Secondary · 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

GroupValue95% CI
Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg0
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg0

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 12 months and 44 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Level 1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 4 mg/kg
Serious: 1/2 (50%)
Deaths: 1/2
Dose Level -1: Ganetespib 100 mg/m^2 + Ziv-Aflibercept 3 mg/kg
Serious: 2/3 (67%)
Deaths: 2/3

Serious adverse events (3 terms)

ReactionSystemDose Level 1: Ganetespib 1…Dose Level -1: Ganetespib …
Rectal perforationGastrointestinal disorders
Small intestinal perforationGastrointestinal disorders
Sudden death Not Otherwise SpecifiedGeneral disorders
Other adverse events (62 terms — click to expand)

ReactionSystemDose Level 1: Ganetespib 1…Dose Level -1: Ganetespib …
AnorexiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
Creatinine increasedInvestigations
DiarrheaGastrointestinal disorders
HematuriaRenal and urinary disorders
NauseaGastrointestinal disorders
Platelet count decreasedInvestigations
Abdominal painGastrointestinal disorders
Abdominal painGastrointestinal disorders
Abdominal painGastrointestinal disorders
Abdominal painGastrointestinal disorders
Activated partial thromboplastin time prolongedInvestigations
Activated partial thromboplastin time prolongedInvestigations
Alanine aminotransferase increasedInvestigations
Alanine aminotransferase increasedInvestigations
Alkaline phosphatase increasedInvestigations
Alkaline phosphatase increasedInvestigations
AnemiaBlood and lymphatic system disorders
AnorexiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Blurred visionEye disorders
BruisingInjury, poisoning and procedural complications
ConstipationGastrointestinal disorders
ConstipationGastrointestinal disorders
ConstipationGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
DizzinessNervous system disorders
Electrocardiogram QT corrected interval prolongedCardiac disorders
Electrocardiogram QT corrected interval prolongedCardiac disorders
Eye infectionInfections and infestations
FatigueGeneral disorders
GastritisGastrointestinal disorders
Gastrointestinal painGastrointestinal disorders
Hemorrhoidal hemorrhageGastrointestinal disorders
HypercalcemiaMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
HypertensionVascular disorders
HypertensionVascular disorders

Most-reported serious reactions: Rectal perforation, Small intestinal perforation, Sudden death Not Otherwise Specified.

Data from ClinicalTrials.gov NCT02192541 adverse events section.

Sponsor's own description

Background: \- 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. Objectives: \- To test the safety and efficacy of the drug combination of ganetespib and ziv-aflibercept. Eligibility: \- Adults age 18 and over with advanced cancer of the colon, lung, urinary tract, and sarcomas. Design: * 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. An update on the status of HSP90 inhibitors in cancer clinical trials.
    Rastogi S, Joshi A, Sato N, Lee S, et al · · 2024 · cited 72× · PMID 38878853 · DOI 10.1016/j.cstres.2024.05.005
  2. Ganetespib: research and clinical development.
    Jhaveri K, Modi S. · · 2015 · cited 70× · PMID 26244021 · DOI 10.2147/ott.s65804
  3. Novel cancer treatment paradigm targeting hypoxia-induced factor in conjunction with current therapies to overcome resistance.
    Kao TW, Bai GH, Wang TL, Shih IM, et al · · 2023 · cited 56× · PMID 37460927 · DOI 10.1186/s13046-023-02724-y
  4. HSP90 multi-functionality in cancer.
    Albakova Z. · · 2024 · cited 32× · PMID 39148727 · DOI 10.3389/fimmu.2024.1436973
  5. Chaperone-assisted E3 ligase CHIP: A double agent in cancer.
    Kumar S, Basu M, Ghosh MK. · · 2022 · cited 29× · PMID 36157498 · DOI 10.1016/j.gendis.2021.08.003
  6. Adipose tissue dysfunction and its effects on tumor metabolism.
    Diedrich J, Gusky HC, Podgorski I. · · 2015 · cited 27× · PMID 25781550 · DOI 10.1515/hmbci-2014-0045
  7. Combined HSP90 and kinase inhibitor therapy: Insights from The Cancer Genome Atlas.
    Schwartz H, Scroggins B, Zuehlke A, Kijima T, et al · · 2015 · cited 20× · PMID 26070366 · DOI 10.1007/s12192-015-0604-1
  8. Heat shock proteins and cancer: The FoxM1 connection.
    Alimardan Z, Abbasi M, Hasanzadeh F, Aghaei M, et al · · 2023 · cited 19× · PMID 36931349 · DOI 10.1016/j.bcp.2023.115505

Verify or expand the search:

Other trials of Ziv-Aflibercept

Trials testing the same drug.

Other recruiting trials for Neoplasms

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02192541.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing