Phase 1 Study of OSI-930 in Cancer Patients

Study Overview
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Brief Summary
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Open label, phase 1, dose escalation

Detailed Description
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Multicenter, open-label, phase 1, dose escalation study to determine the maximum tolerated dose on both once daily (QD) and twice daily (BID) schedules. Patients may continue to receive OSI-930 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.

Official Title
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A Phase I Dose Escalation Study of Daily Oral OSI-930 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: OSI-930
* Drug: OSI-930


Participation Criteria
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Eligibility Criteria
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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. 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 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. 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 Accessible for repeat dosing and follow-up. Patients must practice effective contraceptive measures throughout the study. Provide written informed consent. Exclusion Criteria: 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. Significant cardiac disease unless well controlled, poorly controlled hypertension. Active or uncontrolled infections of serious illnesses or medical conditions that could interfere with participation. History of any psychiatric condition that might impair the patient's ability to provide informed consent or participate. Concurrent anticancer therapy. Use of CYP3A4 inducers/inhibitors during the 14 days prior to first dose. Pregnant or breast-feeding females.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Once Daily Dosing | Drug: OSI-930<br>* Oral OSI-930 administered once daily at increasing doses until disease progression or unacceptable toxicity<br>|
| Experimental: 2<br>Twice Daily Dosing | Drug: OSI-930<br>* Oral OSI-930 administered twice daily at increasing doses until disease progression or unacceptable toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose (MTD) for both the once daily (QD) and twice daily (BID) dosing schedules and establish a recommended phase 2 dose of OSI-930 |  | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, Pharmacokinetic profile, Pharmacodynamic relationships, Preliminary antitumor activity |  | 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Cancer, Non-small cell lung cancer, Small cell lung cancer, Uterine cancer, Ovarian cancer, Renal cancer, Head and neck cancer, Cervical cancer, Metastatic cancer, Colorectal cancer, Gastrointestinal stromal tumors