Crizotinib and Ganetespib (STA-9090) in ALK Positive Lung Cancers

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01579994
First received: April 16, 2012
Last updated: October 1, 2014
Last verified: October 2014
  Purpose

About 18 patients will take part in the phase 1 portion of the trial. In the beginning of the study, 3 patients will be treated with a low dose of ganetespib (STA-9090) and the standard dose of crizotinib. If this dose does not cause significant side effects, it will be increased as new patients take part in the study. The study will only be open at Memorial Sloan Kettering Cancer Center.


Condition Intervention Phase
Advanced Lung Cancer
Drug: Ganetespib (STA-9090) and crizotinib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Crizotinib and Ganetespib (STA-9090) in ALK Positive Lung Cancers

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • maximum tolerated dose [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    A standard 3+3 design will be used to find the maximum tolerated dose (MTD). Patients who withdraw before completing a full cycle will be replaced. There will be three set dose levels, using the approved dose of crizotinib, with 50%, 75% and 100% of the ganetespib (STA-9090) maximum tolerated dose of 200 mg/m2.

  • efficacy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    patients with ALK rearranged NSCLC at delaying acquired resistance to crizotinib by measuring progression free survival


Secondary Outcome Measures:
  • overall survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    as defined by time from study entry to death due to any cause and overall response rate (RR), as defined by the combination of complete responses and partial responses according to RECIST 1.1

  • safety profile [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.


Estimated Enrollment: 55
Study Start Date: April 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ganetespib (STA-9090) and crizotinib
This protocol is a phase I single arm, open label, single institution study of crizotinib and ganetespib (STA-9090) in patients with ALK+ advanced NSCLC who are crizotinib naïve.
Drug: Ganetespib (STA-9090) and crizotinib
Ganetespib (STA-9090) is given intravenously (days 1 and 8 of a 21 day cycle). Crizotinib will be given at the FDA approved dose of 250mg orally twice daily in a continuous fashion.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically proven diagnosis confirmed at MSKCC of advanced lung adenocarcinoma that is locally advanced or metastatic (stage III/IV).
  • Positive for translocation or inversion events involving the ALK gene locus as determined standard methods (including but not limited to by FISH and IHC testing).
  • No prior treatment with crizotinib, but they may have received prior cytotoxic chemotherapy.
  • Age ≥ 18 years.
  • Measurable (RECIST 1.1) indicator lesion not previously irradiated.
  • Karnofsky Performance Status ≥ 70%
  • Able to take oral medications
  • A negative serum pregnancy test obtained within two weeks prior to administration of the experimental agents in all pre-menopausal women (last menstrual period ≤ 24 months ago).
  • All women of child bearing potential (WOCBP) and sexually active men must agree to use adequate methods of birth control throughout the study which include use of oral contraceptives with an additional barrier method, double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy and/or tubal libation and total abstinence.

Exclusion Criteria:

  • Prior crizotinib therapy
  • Inadequate recovery from any toxicity related to prior treatment (to Grade 1 or baseline).
  • Inadequate hematologic function defined as:

    • Absolute neutrophil count (ANC) < 1,000 cells/mm³.
    • Platelet count < 75,000/mm³
    • Hemoglobin < 9.0g/dL.

Inadequate hepatic function defined by:

  • AST and/or ALT > 3x upper limited of normal (ULN).
  • Total bilirubin > 2x ULN.
  • Alkaline phosphatase > 3x ULN.
  • Patients with hepatic metastases may have ALT/AST ≤ 5x ULN.
  • Patients with hepatic and/or bone metastases may have an AP ≤ 5x ULN.
  • Inadequate renal function defined by serum creatinine > 2x ULN Uncontrolled systemic fungal, bacterial, viral or other infection (defined as exhibiting ongoing signs/symptoms related to infection without improvement, despite appropriate anti-infective medications or other treatment).
  • Patients with clinically active brain metastasis (requiring therapy with steroids or radiation therapy). Patients with clinically stable brain metastases (previously treated or untreated) for two weeks are eligible.
  • Significant cardiac disease (e.g. New York Heart Association (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary artery bypass graft (CABG) within the past 6 months; or uncontrolled atrial or ventricular cardiac arrhythmias).
  • Previously or current malignancies at other sites within the last 2 years, with the exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, or prostate cancer that does not require active treatment per National Comprehensive Cancer Network (NCCN) guidelines.
  • Women who are pregnant or lactating
  • Use of drugs or food that are known potent CYP3A4 inhibitors (see Appendix C)
  • Use of drugs that are known potent CYP3A4 inducers (see Appendix D)
  • Any other condition that, in the opinion of the Investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study.
  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: NCT01579994

Contacts
Contact: Gregory Riely, MD PhD 646-888-4199
Contact: Paul Paik, MD 646-888-4202

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: Gregory Riely, MD, PhD    646-888-4202      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Gregory Riely, MD, PhD    646-888-4202      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Gregory J Riely, MD         
Contact: Paul Paik, MD    646-888-4202      
Principal Investigator: Gregory J Riely, MD         
Memorial Sloan-Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Gregory Riely, MD, PhD    646-888-4202      
Memoral Sloan Kettering Cancer Center at Phelps Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Gregory Riely, MD, PhD    646-888-4202      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Gregrory Riely, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01579994     History of Changes
Other Study ID Numbers: 12-015
Study First Received: April 16, 2012
Last Updated: October 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
adenocarcinoma
Lung
Metastatic
Crizotinib
Ganetespib
STA-9090
ALK Positive Lung Cancers
12-015

Additional relevant MeSH terms:
Lung Neoplasms
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Crizotinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 30, 2014