A Phase I/II Study of Crizotinib and STA-9090 in ALK Positive Lung Cancers

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
(resulting in EML4-ALK fusion) 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 or a creatinine
clearance ≤ 60mL/min.

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.