A Phase 1 Dose-escalation Study of OSI-906 and Erlotinib (Tarceva®)

Inclusion Criteria:

Histologically or cytologically confirmed advanced solid tumor
For the NSCLC Expansion Cohort, a confirmed diagnosis of stage IIIB/IV NSCLC after failure of at least 1 prior chemotherapy regimen is required
Patients with Eastern Cooperative Oncology Group (ECOG) performance status Predicted life expectancy >/= 12 weeks

Patients may have had prior therapy, providing certain conditions are met:

Chemotherapy: A minimum of 3 weeks (4 weeks for carboplatin or investigational anticancer agents and 6 weeks for nitrosoureas and mitomycin C) must have elapsed between the end of treatment and registration into this study. Patients must have recovered from any treatment-related toxicities (except for alopecia, fatigue, and grade 1 neurotoxicity) prior to registration.
Hormonal therapy: Patients may have had prior anticancer hormonal therapy provided it is discontinued prior to registration into the study. However, patients with prostate cancer with evidence of progressive disease may continue on therapy that produces medical castration (eg, goserelin or leuprorelin), provided this therapy was commenced at least 3 months earlier.
Radiation: Patients may have had prior radiation therapy provided they have recovered from the acute, toxic effects of radiotherapy prior to registration. A minimum of 21 days must have elapsed between the end of radiotherapy and registration into the study unless the radiation affected less than 25% of bone marrow.
Surgery: Previous surgery is permitted provided that wound healing has occurred prior to registration.
Fasting glucose Blood ketones Neutrophil count >/= 1.5 x 10^9/L
Platelets >/= 100 x 10^9/L
Bilirubin AST and/or ALT Serum creatinine Patients must be nonsmokers (or former smokers who stopped smoking > 3 months previously) and have a negative cotinine test at baseline and on Day 1
Patients in the NSCLC Expansion Cohort must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
Patients in the NSCLC Expansion Cohort will be required to have either an archival or fresh tumor tissue (whole or partial block) available at the start of study
Patients must be accessible for repeat dosing and follow-up, including pharmacokinetic sampling
Patients - both males and females - with reproductive potential must agree to practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test at baseline and on Day 1
Patients must provide verbal and written informed consent to participate in the study

Exclusion Criteria:

Documented history of diabetes mellitus
History of significant cardiac disease unless the disease is well-controlled. Significant cardiac diseases includes second/third degree heart block; significant ischemic heart disease; QTc interval > 450 msec at baseline; poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea)
History of cerebrovascular accident (CVA) within 12 months prior to registration or that is not stable
Prior epidermal growth factor receptor (EGFR) or insulin like growth factor receptor (IGFR) inhibitor therapy, except for prior erlotinib therapy in the NSCLC Expansion Cohort, prior erlotinib therapy will not be exclusionary
History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent
Pregnant or breast-feeding females
Gastrointestinal (GI) abnormalities including inability to take oral medication, requirement for intravenous (IV) alimentation, active peptic ulcer, or prior surgical procedures affecting absorption
Ocular inflammatory or infectious condition that is not completely resolved prior to registration
History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug
Any type of active seizure disorder
Use of drugs that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing
Use of strong or moderate CYP3A4 or CYP1A2 inhibitors/inducers, with the exception of low-dose steroids, within 14 days prior to Day 1 dosing
Use of proton pump inhibitors within 14 days prior to day 1 dosing
Symptomatic brain metastases that are not stable, require steroids, or that have required radiation within the last 28 days
Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's ongoing participation in the study