STA-9090(Ganetespib) in Patients With Unresectable Stage III or Stage IV Melanoma

Phase 2

Terminated

Brief Summary: STA9090 is a drug which inactivates or blocks the work of a protein called Heat Shock Protein 90 or HSP90. HSP90 is a protein that helps some molecules inside your cells to have the right shape. By stopping HSP90's activity, those molecules never get to have the right structure of be functional and they are destroyed. The investigators believe that if they stop the activity of HSP90, the rapidly dividing cells that are in your tumor(s) may slow down. In this research study the investigators are looking to see how well STA9090 works in stopping the spread of your melanoma.

Detailed Description: OBJECTIVES:

Primary

* To determine the proportion of patients alive, free of disease progression, and still taking STA-9090 at 6 months by BRAF mutant or wild type (WT) status.

Secondary

* To assess best overall response rate and six month response rate by BRAF status

* To evaluate the rates of one-year overall survival and progression-free survival by BRAF status

* To determine safety and tolerability of STA-9090 by BRAF status

Exploratory

* To compare the rates of response and of six-month PFS between BRAF status cohorts

* To explore, using peripheral blood mononuclear cells, the relationship between change in expression of hsp90 client proteins (e.g., BRAF, CRAF, AKT, CDK4, KIT) with response to therapy and progression free survival by BRAF status

* To explore the relationship in biopsied melanoma metastases between changes in expression of hsp90 client proteins (e.g., BRAF, CRAF, AKT, CDK4, KIT) with response to therapy and progression-free survival

* To explore response rate and 6 month progression free survival, in subset of patients with melanoma expressing a mutation in KIT

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
STA-9090 Cohort A	STA-9090	Patients enrolled into two possible cohorts based on tumor expression of BRAF: Cohort A - BRAF mutant disease or Cohort B - BRAF wild type. Cohort A patients received STA-9090 200 mg/m2 once weekly (d1, 8, 15 of 28 day cycle). Patients were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.
STA-9090 Cohort B	STA-9090	Patients enrolled into two possible cohorts based on tumor expression of BRAF: Cohort A - BRAF mutant disease or Cohort B - BRAF wild type. Cohort B patients received STA-9090 150 mg/m2 twice weekly (d1, 4, 8, 11, 15, 18 of 28 day cycle). Patients were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.

Primary Outcome Measures

Name	Time	Method
6-month Progression-Free Survival Rate	Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until evidence of disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 6 months.	6-month progression-free survival rate was defined as the proportion of patients absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 6 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

Secondary Outcome Measures

Name	Time	Method
Best Overall Response	Disease was evaluated radiologically at baseline and every 8 weeks on treatment. Median (range) treatment duration was 1 cycle/4 weeks (1-2 cycles; 4-8 weeks).	Best overall response (BOR) on treatment was based on RECIST 1.0 criteria. For target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR confirmation required within 4 weeks. Progressive disease (PD) is at least a 20% increase in the sum LD of target lesions from smallest sum LD as reference or the appearance of one or more new lesions. Stable disease (SD) is neither meeting PR or PD. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. CR is disappearance of all non-target lesions.
Overall Survival	Patients were followed every 4 weeks for survival until death, lost to follow-up or study closure (approximately 6 months after the last patient ended treatment). In this study cohort, patients were followed up to 13 weeks.	Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.

Locations (1): Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States