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

Primary Purpose

Cancer, Small Cell Lung Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ganetespib
Doxorubicin
Sponsored by
Georgetown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Georgetown Lombardi Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Ganetespib and doxorubicin - Phase Ib Dose Level 1

Ganetespib and doxorubicin - Phase Ib Dose Level 2

Ganetespib and doxorubicin - Phase II Expansion

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose
The dose of ganetespib at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity

Secondary Outcome Measures

Objective Response Rate
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.

Full Information

First Posted
October 7, 2014
Last Updated
March 22, 2018
Sponsor
Georgetown University
Collaborators
Synta Pharmaceuticals Corp.
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1. Study Identification

Unique Protocol Identification Number
NCT02261805
Brief Title
A Phase I/II Study of Ganetespib in Combination With Doxorubicin
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Terminated
Why Stopped
Company terminated drug support
Study Start Date
October 2014 (Actual)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Georgetown University
Collaborators
Synta Pharmaceuticals Corp.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ganetespib and doxorubicin - Phase Ib Dose Level 1
Arm Type
Experimental
Arm Description
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
Arm Title
Ganetespib and doxorubicin - Phase Ib Dose Level 2
Arm Type
Experimental
Arm Description
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
Arm Title
Ganetespib and doxorubicin - Phase II Expansion
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Ganetespib
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
The dose of ganetespib at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giuseppe Giaccone, MD PhD
Organizational Affiliation
Georgetown University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgetown Lombardi Comprehensive Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29594044
Citation
Subramaniam DS, Liu SV, Crawford J, Kramer J, Thompson J, Wang H, Giaccone G. A Phase Ib/II Study of Ganetespib With Doxorubicin in Advanced Solid Tumors Including Relapsed-Refractory Small Cell Lung Cancer. Front Oncol. 2018 Mar 12;8:64. doi: 10.3389/fonc.2018.00064. eCollection 2018.
Results Reference
derived

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

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