Study of Oral OSI-027 in Patients With Advanced Solid Tumors or Lymphoma

Study Overview
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Brief Summary
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The primary objective of this study is to determine the maximum tolerated dose (MTD) and to establish the recommended phase 2 dose of oral OSI-027 when administered via 3 schedules, namely, intermittent, weekly, and continuous in patients with advanced solid tumors or lymphoma, namely, intermittent, weekly, and continuous.

Detailed Description
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The study will open with Schedule 1 (S1, intermittent) with initiation of Schedule 2 (S2, weekly) and Schedule 3 (S3, continuous), which may occur in parallel after observation of clinically significant related dose limiting toxicity (DLT) in the S1 schedule. Dosing will be initiated on Day 1 with intermittent weekly dosing continuing for 21 days (1 Treatment Period). Expansion of Dose Escalation Cohorts may occur for S1 and S2 at the recommended phase 2 dose level(s) and a Biomarker Expansion Cohort may be opened in S1 and/or S2.

Official Title
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A Phase 1 Dose-escalation Study of Intermittent, Once Weekly, and Continuous Daily Oral OSI-027 Dosing in Patients With Advanced Solid Tumors or Lymphoma

Conditions
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Any Solid Tumor or Lymphoma

Intervention / Treatment
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* Drug: OSI-027


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented malignancy (solid tumor or lymphoma) Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2 Predicted life expectancy of at least 3 months Adequate hematopoietic and hepatic function, and normal renal function Fasting glucose <7mmol/L at baseline Left ventricular ejection fracture (LVEF) by Multiple gated acquisition scan (MUGA)≥ 60% Practice effective contraceptive measures throughout study Verbal and written informed consent Prior therapy: Chemotherapy, minimum of 3 weeks and recovered from any treatment-related toxicities (except for alopecia, and grade 1 neurotoxicity) prior to registration Hormonal, discontinued prior to registration Radiation, minimum of 21 days and recovered from toxic effects prior to registration Surgery, provided wound healing has occurred Exclusion Criteria: History of significant cardiac disease unless well controlled Discontinuation from prior therapy due to cardiac toxicity Active or uncontrolled infections Serious illness or medical condition that could interfere with study participation History of any psychiatric condition that might impair understanding or compliance Documented history of diabetes mellitus Pregnant or breastfeeding females Unstable symptomatic brain metastases, that require steroid or that have required radiation in the last 28 days Chronic systemic steroid use for cancer related condition History of allergic reactions Patients with cataract who are expected to undergo surgery within 6 months of registration Use of drugs causing QT interval prolongation within 14 days prior to dosing Patients with clinically significant electrolyte imbalances

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: Schedule 1<br>Once daily for 3 days every 7 days | Drug: OSI-027<br>* Administered orally<br>|
| Experimental: Schedule 2<br>Once weekly | Drug: OSI-027<br>* Administered orally<br>|
| Experimental: Schedule 3<br>Once daily | Drug: OSI-027<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile of OSI-027 |  | up to 5 years | 
| Pharmacokinetic profile of OSI-027 |  | up to 23 days | 
| Preliminary pharmacodynamic relationship with OSI-027 systemic exposure |  | up to 23 days | 
| Preliminary antitumor activity of OSI-027 |  | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OSI-027, Solid tumor, Lymphoma