Clinical trial NCT01579994: Crizotinib and Ganetespib (STA-9090) in ALK Positive Lung Cancers
Official title: A Phase I Study of Crizotinib and Ganetespib (STA-9090) in ALK Positive Lung Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Lung Cancer
Keywords: adenocarcinoma
Lung
Metastatic
Crizotinib
Ganetespib
STA-9090
ALK Positive Lung Cancers
12-015
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2012-04-18
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: maximum tolerated dose
timeFrame: 1 year
measure: efficacy
timeFrame: 1 year
Secondary outcomes:
measure: overall survival (OS)
timeFrame: 1 year
measure: safety profile
timeFrame: 2 years
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memoral Sloan Kettering Cancer Center
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center @ Suffolk
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering at Mercy Medical Center
state: New York
city: Sleepy Hollow
country: United States
facility: Memoral Sloan Kettering Cancer Center at Phelps
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Gregrory Riely, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wong KM, Noonan S, O'Bryant C, Jimeno A. Alectinib for the treatment of ALK-positive stage IV non-small cell lung cancer. Drugs Today (Barc). 2015 Mar;51(3):161-70. doi: 10.1358/dot.2015.51.3.2294597.