Multicenter, open-label, phase 1, cohort dose escalation study to determine the MTD of 3 intermittent dosing schedules.

Multicenter, open-label, phase 1, cohort dose escalation. The study will open with S1 (OSI-906 QD Days 1-3 every 14 days). S2 (OSI-906 QD Days 1-5 every 14 days) will be initiated following observation of clinically significant related toxicity >/= grade 2 in S1 or after a review of preliminary safety and PK data from >/= 6 dose levels in S1 indicate that toxicity is acceptable and potential improvement in exposure may be achieved by an increased number of dosing days. S3 (OSI-906 QD Days 1-7 every 14 days) will occur upon observation of clinically significant related toxicity >/= grade 2 in S2 or after >/= 1 dose level in S2 has been examined. In each schedule, a single dose will be administered on each of the specified days followed by a drug-free period through to Day 14. A treatment period is defined as 14 days. Patients may continue to receive OSI-906 until one of the following occurs: disease progression, adverse event requiring withdrawal, failure to recover from toxicity despite a 14-day dosing interruption, medical or ethical reasons, patient request, or patient death.

• Experimental: Schedule 1 (OSI-906 days 1-3 every 14 days)
• Experimental: Schedule 2 (OSI-906 days 1-5 every 14 days)
• Experimental: Schedule 3 (OSI-906 days 1-7 every 14 days)

Inclusion Criteria:

• Histologically or cytologically documented malignancy that is now advanced and/or metastatic and refractory to established forms of therapy or for which no effective therapy exists.
• History of allergic reaction attributed to a similar compound as study drug.
• Potassium, calcium, and magnesium must be within normal limits (WNL). Electrolyte abnormalities will be permitted if they are not clinically significant and if treatment for the abnormality is initiated prior to Day 1.
• ANC >/= 1.5 x 10^9/L, PLT >/= 100 x 10^9/L;
• bilirubin </= 1.5 x upper limit of normal (ULN), AST and ALT </= 2.5 x ULN;
• creatinine </= 1.5 ULN
• Age >/= 18 years, ECOG PS 0-2,
• life expectancy >/= 12 weeks
• Prior chemotherapy is permitted provided that a minimum of 3 weeks has elapsed. Prior tyrosine kinase inhibitor therapy is permitted.
• Patients must have recovered from any treatment-related toxicities (with some exceptions) prior to registration.
• Prior hormonal therapy is permitted provided it is discontinued prior to registration (with the exception of prostate cancer patients who have been on hormone therapy for at least 3 months).
• Prior radiation therapy is permitted provided that patients have recovered from the toxic effects.
• A minimum of 21 days must have elapsed unless the radiotherapy was palliative and nonmyelosuppressive.
• Fasting glucose </= 125 mg/dL (7 mmol/L) at baseline
• History of any kind of stroke.
• History of any psychiatric condition that might impair the patient's ability to provide informed consent or participate.
• Accessible for repeat dosing and follow-up, including pharmacokinetic sampling.
• Patients must practice effective contraceptive measures throughout the study.
• Provide written informed consent.
• History of significant cardiac disease unless well controlled (includes 2nd/3rd degree heart block, ischemic heart disease, QTc > 450 msec, poorly controlled hypertension, and congestive heart failure of New York Heart Association (NYHA) Class II or worse

Exclusion Criteria:

• Any type of active seizure disorder.
• Concurrent anticancer therapy.
• Use of drugs with a risk of causing QT interval prolongation within 14 days prior to Day 1 and while on study.
• Use of glucocorticoids within 14 days prior to Day 1 and while on study.
• Previously diagnosed brain metastases.
• Documented history of diabetes mellitus.
• Active or uncontrolled infections of serious illnesses or medical conditions that could interfere with participation.
• Pregnant or breast-feeding females.