A Study Of Oral PF-02341066, A c-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

• To test the safety of PF-02341066 when taken by people who have cancer [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]
• To assess how the body handles blood concentrations of PF-02341066 [ Time Frame: 2.0 years ] [ Designated as safety issue: No ]
• To find the dose of PF-02341066 that should be used in future clinical trials [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]

• Anti-tumor activity [ Time Frame: 4.0 years ] [ Designated as safety issue: No ]
• To assess how the body handles blood concentrations of PF-02341066 in the presence of another drug, rifampin [ Time Frame: 2.0 years ] [ Designated as safety issue: No ]
• To assess how the body handles blood concentrations of PF-02341066 in the presence of another drug, ketoconazole [ Time Frame: 3.0 years ] [ Designated as safety issue: No ]

PF-02341066 may work in cancer by blocking the cell growth, migration and invasion of tumor cells. PF-02341066 is a new class of drugs called c-Met/Hepatocyte growth factor receptor tyrosine kinase inhibitors. This compound is also an inhibitor of the anaplastic lymphoma kinase (called ALK) tyrosine kinase and ROS receptor tyrosine kinases. This research study is the first time PF-02341066 will be given to people. PF-02341066 is taken by mouth daily.

• Systemic Anaplastic Large-Cell Lymphoma
• Neoplasms
• Anaplastic Lymphoma Kinase, Human
• NSCLC

• Drug: PF-02341066
  Escalating doses of PF-02341066 will be administered orally on a continuous dosing schedule. Doses to be evaluated will range from 50 mg to 2000 mg/day administered either once or twice a day. A treatment cycle is considered to be 28 days (or 21 days depending on the cohort).
• Drug: Rifampin
  600 mg QD administered from Cycle 1, Day 16 to Cycle 2, Day 1 (14 days of dosing) in combination with PF-02341066.
• Drug: Ketoconazole
  200 mg BID administered from Cycle 1, Day 16 to Cycle 2, Day 1 (Cycle 2, Day 1 morning dose only; 13.5 days of dosing) in combination with PF-02341066.

• Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, Riely GJ, Solomon B, Ou SH, Kim DW, Salgia R, Fidias P, Engelman JA, Gandhi L, Jänne PA, Costa DB, Shapiro GI, Lorusso P, Ruffner K, Stephenson P, Tang Y, Wilner K, Clark JW, Shaw AT. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012 Oct;13(10):1011-9. doi: 10.1016/S1470-2045(12)70344-3. Epub 2012 Sep 4.
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Inclusion Criteria:

• Advanced malignancies (except leukemias), histologically proven at diagnosis; Histologically confirmed advanced malignancies that are known to be sensitive to PF-03241066 inhibition, e.g. ALK, c-MET and ROS
• Solid tumors must have measurable disease (Recommended Phase 2 Dose Cohort patients with non-measurable disease may enter on a case-by-case basis); not required for DDI sub-studies.
• Adequate blood cell counts, kidney function, liver function and Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (for the Recommended Phase 2 Cohort, a ECOG score of 2 may be allowed on a case-by-case basis)

Exclusion Criteria:

• Major surgery, radiation therapy or anti-cancer therapy within 2 to 4 weeks of starting study treatment, depending on the patient cohort
• Prior stem cell transplant except of patients with neuroblastoma, lymphoma or myeloma
• Active or unstable cardiac disease or heart attack within 6 months of starting study treatment