A Phase I/II Study of Ganetespib in Combination With Doxorubicin

March 22, 2018 updated by: Georgetown University

A Phase I/II Study of Ganetespib in Combination With Doxorubicin in Solid Tumors (Phase I) and Refractory Small Cell Lung Cancer (Safety Dose Expansion, Phase II)

This is a Phase I/safety dose expansion study of the combination of the drug ganetespib and doxorubicin in patients with advanced solid tumors. The purpose of the Phase I part of the study is to determine the recommended phase II dose of ganetespib when given in combination with doxorubicin. The recommended Phase II dose determined at the end of the dose escalation phase will be used to conduct a safety dose expansion phase in relapsed/refractory small cell lung cancer to determine if there is a signal of efficacy in this population.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The dose escalation phase of the study will follow a standard 3+ 3 dose escalation scheme with two dose levels of ganetespib (1-- mg/m2 and 150 mg/m2) administered weekly on Days 1 and 8 of a 21-day cycle, in combination with a fixed dose of doxorubicin at 50 mg/m2 administered on Day 1 alone. After 4-6 cycles of combination therapy, continuation of single agent ganetespib will be permitted for subjects who are deriving clinical benefit.

Pharmacokinetic samples for plasma drug levels of ganetespib will be collected pre-dose and 4 hours after completion of treatment on Day 1 and Day 8 of cycle 1 only in subjects in the dose escalation phase.

The recommended Phase II dose determined at the end of the dose escalation phase will be used to conduct a safety dose expansion phase in relapsed/ refractory small cell lung cancer to determine if there is a signal of efficacy in this population.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown Lombardi Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Dose escalation phase: histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. OR safety dose expansion phase: histologically or cytologically confirmed relapsed or refractory small cell lung cancer
  • No more than 3 prior lines of chemotherapy; prior therapy with doxorubicin is permitted but no more than lifetime cumulative dose of 150 mg/m2; at least 3 weeks since prior chemotherapy or radiotherapy; at least 6 weeks if the last regimen included BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea bis-chloronitrosourea) or mitomycin C
  • Age >/= 18 years
  • ECOG (Eastern Cooperative Oncology Group) performance status 0-1
  • Life expectancy of greater than 3 months
  • Adequate organ and marrow function
  • Women of child-bearing potential must agree to avoid becoming pregnant and men must agree not to father a child for the duration of study participation.
  • Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

  • Chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosureas 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.
  • Receiving any other investigational agents
  • Untreated symptomatic brain metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ganetespib or other agents used in the study
  • Receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or CYP2C18
  • Left ventricular ejection fraction < 50%
  • Known serious cardiac illness or medical conditions
  • uncontrolled inter-current illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women
  • HIV-positive on combination antiretroviral therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ganetespib and doxorubicin - Phase Ib Dose Level 1
Ganetespib 100 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle
Drug: Doxorubicin
Other Names:
  • Adriamycin
Drug: Ganetespib
Experimental: Ganetespib and doxorubicin - Phase Ib Dose Level 2
Ganetespib 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle
Drug: Doxorubicin
Other Names:
  • Adriamycin
Drug: Ganetespib
Experimental: Ganetespib and doxorubicin - Phase II Expansion
Ganetespib 150 mg/m2 IV on days 1 and 8 of a 21-day cycle Doxorubicin 50 mg/m2 IV on day 1 of a 21-day cycle
Drug: Doxorubicin
Other Names:
  • Adriamycin
Drug: Ganetespib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose
Time Frame: 1 year
The dose of ganetespib at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: 2 years
Objective response rate included the count of confirmed complete responses (CR) and partial responses (PR) and was based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Georgetown University

Collaborators

Synta Pharmaceuticals Corp.

Investigators

  • Principal Investigator: Giuseppe Giaccone, MD PhD, Georgetown University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2014

Primary Completion (Actual)

October 1, 2016

Study Completion (Actual)

October 1, 2016

Study Registration Dates

First Submitted

October 7, 2014

First Submitted That Met QC Criteria

October 7, 2014

First Posted (Estimate)

October 10, 2014

Study Record Updates

Last Update Posted (Actual)

April 23, 2018

Last Update Submitted That Met QC Criteria

March 22, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013-1195

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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