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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Cancer, Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Ganetespib
* Drug: Doxorubicin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ganetespib and doxorubicin - Phase Ib Dose Level 1<br>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: Ganetespib<br> <br> Drug: Doxorubicin<br> <br> * Other names: Adriamycin;|
| Experimental: Ganetespib and doxorubicin - Phase Ib Dose Level 2<br>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: Ganetespib<br> <br> Drug: Doxorubicin<br> <br> * Other names: Adriamycin;|
| Experimental: Ganetespib and doxorubicin - Phase II Expansion<br>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: Ganetespib<br> <br> Drug: Doxorubicin<br> <br> * Other names: Adriamycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | 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 | 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 |