STA-9090(Ganetespib) in Metastatic Ocular Melanoma

NCT01200238 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 10-137
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

STA-9090, a synthetic small molecule, demonstrates significant activity for down-regulating Heat Shock Protein 90 or Hsp90 levels. Hsp90 belongs to a class of molecular chaperone proteins known to be critical regulators of cancer cell proliferation and survival. Preclinical laboratory experiments have shown STA-9090, an Hsp90 inhibitor, could inhibit ocular melanoma cell lines. The primary objective of this trial is to obtain evaluations of STA-9090 efficacy to metastatic ocular melanoma.

Conditions

Ocular Melanoma

Keywords

STA9090; STA-9090; HSP90

Outcome Measures

Primary Outcomes (2)

• 4-month Progression Free Survival (PFS) Rate

  4-month PFS rate was defined as the proportion of participants alive, absent progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) and on treatment at 4 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. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

  Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Relevant for this endpoint was status at 4 months.

• Expression of cMET

  To estimate the proportion of patients with greater than 50% decrease in expression of HSP90 client protein c-MET 18-24 hours after administration of STA-9090

  Estimated up to 24 hours after administration of STA-9090

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Median treatment duration was 1.8 months for each cohort [range: cohort A (0.9-12.5), cohort B (0.8-31.7)]. Thus, response on treatment was evaluated up to 31.7 months.

• Disease Control Rate (DCR)

  Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Median treatment duration was 1.8 months for each cohort [range: cohort A (0.9-12.5), cohort B (0.8-31.7)].Thus, response on treatment was evaluated up to 31.7 months.

• Progression-Free Survival (PFS)

  Dz was evaluated every 8 weeks on treatment; Imaging was obtained as clinically indicated until off-study; Median (range) on-study duration (months) was cohort A: 8.7 (3.7 to 28.7) and cohort B: 4.5 (1.2 to 36.4 months). Thus, follow-up was up to 36.4m.

• Overall Survival (OS)

  Survival follow-up occurred every 4 weeks long-term; Median (range) on-study duration (months) was cohort A: 8.7 (3.7 to 28.7) and cohort B: 4.5 (1.2 to 36.4 months).Thus, follow-up was up to 36.4m.

• Grade 3-4 Treatment-Related Toxicity Rate

  AE assessment was ongoing from the start of study drug and up to day 30 post-treatment. Mean treatment duration was 1.8 months for each cohort [range: cohort A (0.9-12.5), cohort B (0.8-31.7)). Thus, AEs on treatment were followed up to 31.7 months.

Study Arms (2)

STA-9090: Cohort A

EXPERIMENTAL

Cohort A participants received STA-9090 200 mg/m2 given intravenously (IV) over 1 hour once weekly (d1, 8, 15 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.

Drug: STA-9090

STA-9090: Cohort B

EXPERIMENTAL

Cohort B participants received STA-9090 150 mg/m2 given intravenously over 1 hour (IV) twice weekly (d1, 4, 8, 11, 15, 18 of a 28 day cycle). Participants were treated until evidence of disease progression, unacceptable toxicity, intercurrent illness or withdrawal.

Drug: STA-9090

Interventions

STA-9090 DRUG

Also known as: Ganetespib

STA-9090: Cohort A; STA-9090: Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed stage IV ocular melanoma
• ECOG Performance status 0, 1, or 2
• years of age or older
• Laboratory values as indicated in the protocol
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
• Presence of metastatic disease that would be amenable to the required biopsies
• At least one site of measurable disease as defined by at least 1cm in greatest dimension. This site must be different from the sites to be used for biopsy. No prior radiation therapy or directed ablation to the site of measurable disease

You may not qualify if:

• Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Major surgery within 4 weeks prior to first dose of STA-9090
• Minor surgery within 7 days of first dose of STA-9090
• Embolization procedure or ablation procedure to treat tumor within 4 weeks of first dose
• Participants may not be receiving any other investigational agents
• Poor venous access for study drug administration unless patient can use silicone based catheters
• History of brain metastases or of leptomeningeal involvement
• History of allergic reactions or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to STA-9090
• Baseline QTc \> 450 msec or previous history of QT prolongation while taking other medications
• Ventricular ejection fraction (EF) of 55% or less at baseline
• Treatment with chronic immunosuppressants
• Melanoma of cutaneous, mucosal or acral-lentiginous origin or of unknown primary
• Prior treatment with HSP90 inhibitor
• Not willing to undergo biopsy before and after treatment
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Beth Israel Deaconess Medical Center: collaborator
• Massachusetts General Hospital: collaborator
• Brigham and Women's Hospital: collaborator
• Synta Pharmaceuticals Corp.: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Uveal Melanoma

Interventions

STA 9090

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Limitations and Caveats

The study was terminated early due to slow accrual and competing trials.

Results Point of Contact

• Title: F. Stephen Hodi, MD
• Organization: Dana-Farber Cancer Institute

Stephen_Hodi@dfci.harvard.edu

617.632.5053

Study Officials

• F. Stephen Hodi, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Melanoma Disease Center Director

Model Details: The original dose (Cohort A) was amended based on phase 1 data for safety. Therefore there are 2 separate arms reported.

Study Record Dates

• First Submitted: September 10, 2010
• First Posted: September 13, 2010
• Study Start: September 17, 2010
• Primary Completion: October 12, 2014
• Study Completion: November 11, 2016
• Last Updated: October 18, 2018
• Results First Posted: June 27, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)