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.

Study Overview

• Status: Completed
• Conditions: Any Solid Tumor or Lymphoma
• Intervention / Treatment: Drug: OSI-027

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University Hospitals Leuven
• United Kingdom
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Mardsen Hospital
• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Schedule 1; Once daily for 3 days every 7 days	Drug: OSI-027; Administered orally
Experimental: Schedule 2; Once weekly	Drug: OSI-027; Administered orally
Experimental: Schedule 3; Once daily	Drug: OSI-027; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose	21 days

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: June 13, 2008
• First Submitted That Met QC Criteria: June 16, 2008
• First Posted (Estimate): June 17, 2008

Study Record Updates

• Last Update Posted (Estimate): April 15, 2013
• Last Update Submitted That Met QC Criteria: April 11, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Lymphoma; Solid tumor; OSI-027
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: OSI-027-101; 2007-006158-25 (EudraCT Number)