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

Stopped early · Phase 1

Conditions studied: Neoplasms

In brief

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.

Key facts

Study ID

NCT02192541

Run by

National Cancer Institute (NCI)

People needed

5

Starts

2014-12-02

Expected to finish

2016-02-25

Last updated by the study team

2018-03-29

Who can join

Age: 18 and older, up to 120. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
• Patients who are receiving any other investigational agents.
• Patients with known active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients whose brain metastatic disease status has remained stable for greater than or equal to 4 weeks following treatment of brain metastases are eligible to participate at the discretion of the principal investigator.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active untreated infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with known serious cardiac illness or medical conditions, including but not
• limited to:
• Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, unstable angina or history of myocardial infarct within 6 months prior to enrollment, or indwelling temporary pacemaker
• Ventricular tachycardia or a supraventricular tachycardia that requires treatment with antiarrhythmic agents
• Second- or third-degree atrioventricular block unless treated with a permanent pacemaker
• Complete left bundle branch block
• History of long Q wave, T wave (QT) syndrome or a family member with this condition
• No major surgery within 4 weeks prior to enrollment or history of gastrointestinal bleeding within 3 months prior to enrollment. No signs or symptoms of active bleeding or nonhealing ulcer will be permitted at study entry. Patients with central pulmonary tumors with evidence of bronchial invasion, or presenting with hemoptysis will be excluded.
• Corrected QT interval (QTc) > 470 msec on electrocardiogram (by Bazett's; average of triplicate recordings at the discretion of the principal investigator (PI) will exclude patients from entry on study. Medications that are known to cause QTc interval prolongation are prohibited for patients entering on trial. Patients for whom a given medication that may cause QTc interval prolongation cannot be discontinued, may be eligible at the discretion of the study PI, provided QTc interval criteria is met at enrollment. A comprehensive list of agents with the potential to cause QTc prolongation can be found in Appendix C and at http://crediblemeds.org.
• Pregnant women and women who are breastfeeding are excluded from this study because the effects of the study drugs on the developing fetus are unknown.
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ganetespib and zivaflibercept. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Substrates of cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C19 (CYP2C19):
• Preliminary results of a clinical drug-drug interaction study, examining the effect of ganetespib on the pharmacokinetics of the CYP2C19-sensitive probe omeprazole, show a modest (20%) increase in omeprazole exposure when coadministered with ganetespib.
• In vitro data implies expectation of greater interaction with CYP2C19 substrates than with CYP3A4 substrates.
• Caution is advised when sensitive narrow therapeutic range CYP3A4 or CYP2C19 substrates are concomitantly administered.
• Inhibitors of P-Glycoprotein Efflux Transporters: Concomitant medications that are strong inhibitors of P-glycoprotein efflux transporters should be used with caution during the study; examples of these medications include:
• ritonavir,
• cyclosporine,
• verapamil,
• erythromycin,
• ketoconazole,

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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