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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT01579994

Collaborator

(none)

Enrollment

Locations

Arm

104.4

Actual Duration (Months)

2.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Advanced Lung Cancer	Drug: Ganetespib (STA-9090) and crizotinib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of Crizotinib and Ganetespib (STA-9090) in ALK Positive Lung Cancers

Actual Study Start Date :

Apr 16, 2012

Actual Primary Completion Date :

Dec 28, 2020

Actual Study Completion Date :

Dec 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

Outcome Measures

Primary Outcome Measures

maximum tolerated dose [1 year]
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 [1 year]
patients with ALK rearranged NSCLC at delaying acquired resistance to crizotinib by measuring progression free survival

Secondary Outcome Measures

overall survival (OS) [1 year]
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 [2 years]
Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Memoral Sloan Kettering Cancer Center	Basking Ridge	New Jersey	United States
2	Memorial Sloan Kettering Cancer Center @ Suffolk	Commack	New York	United States	11725
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	Memorial Sloan Kettering at Mercy Medical Center	Rockville Centre	New York	United States
5	Memoral Sloan Kettering Cancer Center at Phelps	Sleepy Hollow	New York	United States	10591