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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Synta Pharmaceuticals Corp.
Information provided by (Responsible Party):
F. Stephen Hodi, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01551693
First received: April 29, 2011
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Melanoma
Drug: STA-9090
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of the HSP90 Inhibitor STA-9090 in Patients With Unresectable Stage III or Stage IV Melanoma Who Received Prior Tyrosine Kinase Inhibitor Treatment

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Survival and disease free progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the proportion of patients alive, free of disease progression, and still taking STA-9090 at 6 months in patients with stage III unresectable or stage IV melanoma in each BRAF cohort


Secondary Outcome Measures:
  • Overall response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess best overall response rate and six month response rate of STA-9090 in patiens with stage III unresectable or stage IV melanoma in each BRAF cohort.

  • One-year overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the rates of one-year overall survival and progression-free survival in each cohort.

  • Safety and tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine safety and tolerability of STA-9090 in subjects with melanoma in each BRAF cohort, evaluating disease progression by tumor measurement and the review of applicable adverse events.

  • 6 month response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess six month response rate of STA-9090 in patiens with stage III unresectable or stage IV melanoma in each BRAF cohort.


Estimated Enrollment: 50
Study Start Date: September 2011
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mutant V600E BRAF Arm Drug: STA-9090
200 mg/m^2 IV over 1 hours +/- 15 min, on days 1, 8 15 of 28 day cycle
Experimental: Wild-type BRAF Expressing Melanoma Arm Drug: STA-9090
200 mg/m^2 IV over 1 hours +/- 15 min, on days 1, 8 15 of 28 day cycle

Detailed Description:

STA-9090 will be given intravenously over 1 hour. Treatment will be given in cycles which last 28 days (4 weeks). Study drug will be given once a week for the first 3 weeks (days 1, 8 and 15) and not during the last week.

Subjects will receive a clinical exam, ECG (before and after study drug) and blood tests on days when they receive the study drug. In Cycle 1, subjects will have a biopsy and blood samples taken on Day 2.

20 to 30 days after the last study treatment, subjects will have a clinical exam, ECG, blood tests, pregnancy test (if applicable), tumor assessment by CT, urine sample and possible biopsy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • Histologically confirmed unresectable stage III or stage IV melanoma
  • Treatment of unresectable stage III or stage IV melanoma with a tyrosine kinase inhibitor within prior 4 months. Sorafenib for purposes of eligibility will not be considered acceptable prior therapy
  • Sufficient tumor available to determine if expresses wild-type or mutated BRAF if result not already known. The presence or absence of BRAF mutation needs to be determined at BWH, MGH, BIDMC, by Drs. Christopher Corless and Michael Heinrich at Cancer Pathology Shared Resource Oregon Health & Science University, or in context of eligibility assessment after signing consent to a previous clinical trial
  • Sufficient tumor available to determine if expresses a mutation KIT
  • Agreement to allow tumor to be evaluated for mutations in KIT and BRAF
  • ECOG performance status ≤ 1
  • Life expectancy of ≥ 6 months
  • Age ≥ 18 years
  • WBC ≥ 3 x 103/ul
  • ANC ≥ 1,500/ul
  • Platelets ≥ 100 x 103/ul
  • Hemoglobin ≥ 9 gm/dl
  • Serum creatinine ≤ 1.5 x ULN
  • Calculated creatinine clearance ≥ 60 mL/min
  • AST ≤ 2.5 x ULN; -OR- AST ≤ 5 x ULN in the presence of known liver metastases
  • ALT ≤ 2.5 x ULN; -OR- ALT ≤ 5 x ULN in the presence of known liver metastases
  • Total bilirubin ≤ 1.5 x ULN
  • Potassium within normal range or correctable with supplements
  • Magnesium within normal range or correctable with supplements
  • Corrected serum calcium within normal range, or correctable with supplements
  • Not pregnant or breastfeeding. Female subjects of childbearing age must have a negative serumpregnancy test at study entry
  • Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation and for 6 months following last study drug administration
  • Agreement to provide blood samples for pharmacodynamic studies utilizing Peripheral Blood Mononuclear Cells (PMBCs) as outlined in protocol
  • At least one site of measurable disease as defined by at least 1 cm 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 measureable disease
  • Able to understand and willing to sign a written informed consent document
  • Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
  • No chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study entry
  • No radiotherapy within 4 weeks prior to study entry
  • Subject has recovered from adverse events due to agents administered more than 4 weeks earlier
  • No tyrosine kinase inhibitor within 14 days prior to study entry
  • No major surgery within 4 weeks prior to first dose of STA-9090
  • No minor surgery within 7 days of first dose of STA-9090
  • No history of or current coronary artery disease, myocardial infarction, angina pectoris, angioplasty
  • or coronary bypass surgery
  • No current treatment with the following antiarrythmic drugs: flecainide, moricizine or propafenone
  • No NYHA class II/III/IV congestive heart failure with a history of dyspnea, orthopnea, or edema that requires current treatment with angiotensin convering enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, or diuretics
  • No current or prior radiation to the left hemithorax
  • No embolization procedure or ablation procedure to treat tumor within 4 weeks of first dose of STA- 9090
  • Not receiving any other investigational agents
  • No poor venous access for study drug administration unless subject can use silicone based catheters
  • No history of brain metastases or of leptomeningeal involvement
  • No history of severe allergic reactions or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to STA-9090 (e.g. olyethylene glycol [PEG] 300 or Polysorbate 80)
  • Baseline QTc ≤ 470 msec
  • No previous history of QT prolongation while taking other medications
  • Ventricular ejection fraction (EF) > 55%
  • No treatment with chronic immunosuppressants
  • No melanoma of ocular primary
  • No prior treatment with hsp90 inhibitor
  • No uncontrolled intercurrent illness including, but not limited to ongoing or active infection, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • No other medications, or severe acute/chronic medical of psychiatric conditions or laboratory abnormality that may increase the risk associated with the study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into the study
  • No history of a different malignancy except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
  • No HIV-positive subject on combination antiretroviral therapy
  • No more than 3 prior systemic therapies for unresectable stage III or stage IV melanoma
  • No concomitant use of medications associated with a high incidence of QT prolongation as outlined
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01551693

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
Synta Pharmaceuticals Corp.
Investigators
Principal Investigator: F. Stephen Hodi, M.D. Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: F. Stephen Hodi, MD, Melanoma Disease Center Director, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01551693     History of Changes
Other Study ID Numbers: 11-039
Study First Received: April 29, 2011
Last Updated: February 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Stage III
Stage IV
Unresectable
Metastatic

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on October 20, 2014