Cancer, Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGGanetespib
DRUGDoxorubicin
Sponsors
Synta Pharmaceuticals Corp.
Georgetown University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose | 1 year | The dose of ganetespib at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ganetespib and Doxorubicin Ganetespib 100 or 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 and doxorubicin
Ganetespib and doxorubicin: IV ganetespib and doxorubicin | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Ganetespib and Doxorubicin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 1 / 11 |
Outcome results
Primary
Maximum Tolerated Dose
The dose of ganetespib at which 1 or more out of 3-6 patients experiences a dose-limiting toxicity
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ganetespib and Doxorubicin - Phase Ib Dose Level 1 | Maximum Tolerated Dose | 100 mg/m^2 |
| Ganetespib and Doxorubicin - Phase Ib Dose Level 2 | Maximum Tolerated Dose | 150 mg/m^2 |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ganetespib and Doxorubicin - Phase Ib Dose Level 1 | Objective Response Rate | 1 Participants |
| Ganetespib and Doxorubicin - Phase Ib Dose Level 2 | Objective Response Rate | 1 Participants |
| Ganetespib and Doxorubicin - Phase II Expansion | Objective Response Rate | 0 Participants |