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

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

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.

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.

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