Phase I Study of OSI-930 and Erlotinib in Cancer Tumors

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

This is a Phase I, dose escalation, safety study of OSI-930 and Erlotinib in cancer tumors.

Multicenter, open-label, phase 1, dose escalation study to determine the maximum tolerated dose of OSI-930 and Erlotinib.

Patients may continue to receive OSI-930 and Erlotinib 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.

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