A Phase 1 Dose Escalation Study of Daily Oral OSI-930 and Erlotinib (Tarceva) in Patients With Advanced Solid Tumors

Inclusion Criteria:

- Histology 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

- Age greater than or equal to 18 years

- ECOG PS 0-2

- ANC greater than or equal to 1.5 x 10^9/L

- Bilirubin less than or equal to 1.5 x upper limit of normal (ULN), AST and ALT less
than or equal to 2.5 x ULN

- Creatinine less than or equal to 1.5 ULN

- Predicted life expectancy greater than or equal to 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 it did not exceed 25% of bone
marrow reserve and patients have recovered from the toxic effects (a minimum of 21
days must have elapsed unless the radiotherapy was palliative and
nonmyelosuppressive)

- Prior surgery is permitted, provided that wound healing has occurred prior to
registration

- Patients must use proactive effective contraceptive measures throughout the study

- Provide written informed consent

- Accessible for repeat dosing and follow-up

- Adequate hematopoietic, hepatic, and renal function

Exclusion Criteria:

- Significant cardiac disease unless well controlled

- Current or former smokers, unless patients stopped smoking greater than 3 months
prior to registration

- Active or uncontrolled infections of serious illnesses or medical conditions that
could interfere with participation

- History of unacceptable toxicity with previous EGFR inhibitor therapy

- History of any psychiatric condition that might impair the patient's ability to
provide informed consent or participate

- Use of CYP3A4 inducers/inhibitors during the 14 days prior to first dose

- Pregnant or breast-feeding females

- Symptomatic brain metastases which are not stable, require steroids, are potentially
life-threatening or that have required radiation within the last 28 days

- History of allergic reaction attributed to a similar compound as study drug

- GI abnormalities including inability to take oral medications, required for IV
alimentation

- Clinically significant ophthalmologic abnormalities