A Trial To Assess Safety And Tolerability Of PF-04691502 In Cancer Patients

Inclusion Criteria

• •Patients with a histologically or cytologically confirmed malignant solid tumor for which there is no currently approved treatment or which is unresponsive to currently approved therapies.
• •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
• •Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours of the first dose of PF-04961502, These patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter. Male patients or their partners must be surgically sterile or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate
• •Adequate Bone Marrow Function, including:
• •1. Absolute neutrophil count (ANC) ≥1500 cells/mm3
• •2. Platelets ≥75,000 cells/mm3
• •3. Hemoglobin ≥9 mg/dL
• •Adequate Renal Function, including:
• •SrCr \<1.5 x ULN (upper limit of normal). OR Estimated creatinine clearance ≥60 mL/min, as calculated using method standard for the institution
• •Adequate Liver Function, including:
• •Bilirubin ≤1.5 x ULN AST (SGOT) ≤2.5 x ULN ALT (SGPT) ≤2.5 x ULN
• •Adequate glucose control, including no previous diagnosis of diabetes mellitus and HbA1c \<7%.
• •Adequate Cardiac Function, including:
• •12-Lead electrocardiogram (ECG) with normal tracing or non clinically significant changes that do not require medical intervention. QTc interval ≤470 msec and no history of Torsades des Pointes or other symptomatic QTc abnormality
• •Chemotherapy, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, ie, non target lesions), biological or investigational agents within 2 weeks of Baseline disease assessments
• •Any surgery (not including minor procedures such as lymph node biopsy) within 4 weeks of Baseline disease assessments; or not fully recovered from any side effects of previous procedures
• •Prior therapy with an agent that is known or proposed to be active by action on PI3K and/or mTOR
• •Prior high-dose chemotherapy requiring hematopoetic stem cell transplantation within 12 months of study treatment start
• •Uncontrolled or significant cardiovascular disease:
• •Current use or anticipated need for food or drugs that are known potent CYP3A4 inhibitors or inducers
• •Current use or anticipated need for food or drugs that are known potent CYP1A2 inhibitors or inducers
• •Concurrent administration of herbal preparations
• •Breast feeding: No studies have been conducted in humans to assess the impact of PF-04691502 on milk production, its presence in breast milk and its effects on the breast-fed child. Because drugs are commonly excreted in human milk and because of the potential for serious adverse reactions in nursing infants, lactating female patients are excluded from this study.
• •Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medication in tablet form and malabsorption syndrome.
• •Any mental disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol