Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

OSI-7904L and Oxaliplatin in Treating Patients With Refractory or Recurrent Advanced Colorectal Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over Other, Pharmaceutical / Industry EORTC-16033 OSI-EORTC-16033, NCT00081237

Objectives

Primary

1. Determine the dose-limiting toxicity of OSI-7904L and oxaliplatin in patients with refractory or recurrent advanced colorectal cancer.
2. Determine the maximum tolerated dose of this regimen in these patients.
3. Determine a safe dose for this regimen in these patients.

Secondary

1. Determine the pharmacokinetic profile of this regimen in these patients.
2. Determine the safety profile of this regimen in these patients.
3. Determine the antitumor activity of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed colorectal cancer
  • Radiologic evidence of advanced disease



• At least 1 measurable lesion at least 20 mm OR at least 10 mm by spiral CT scan
  • Indicator lesions in a previously irradiated field are allowed provided the irradiated lesion has clearly progressed OR a new lesion has developed in the irradiated field



• Failed 1, and only 1, line of prior chemotherapy for advanced/metastatic disease
  • Disease progression during chemotherapy OR within 6 months after completion of treatment



• No symptomatic brain metastases meeting any of the following criteria:
  • Unstable
  • Inadequately controlled with fixed-dose oral steroids
  • Potentially life-threatening
  • Required radiotherapy with the past 28 days

Prior/Concurrent Therapy:

Biologic therapy

• At least 21 days since prior immunotherapy
• At least 21 days since prior monoclonal antibody therapy

Chemotherapy

• See Disease Characteristics
• At least 21 days since prior chemotherapy and recovered*
• No prior oxaliplatin

 [Note: *Alopecia allowed]

Endocrine therapy

• See Disease Characteristics
• At least 21 days since prior hormonal therapy

Radiotherapy

• See Disease Characteristics
• At least 21 days since prior radiotherapy and recovered
• No prior radiotherapy to more than 25% of bone marrow reserve

Surgery

• Recovered from prior surgery

Other

• At least 21 days since prior tyrosine kinase inhibitor therapy
• More than 21 days since prior investigational agents
• No other concurrent anticancer therapy
• No other concurrent investigational agents

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count > 1,500/mm³
• Platelet count > 100,000/mm³

Hepatic

• AST and ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• Bilirubin < 1.5 times ULN
• No hepatitis
• No cirrhosis

Renal

• Creatinine < 1.5 times ULN

Other

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• HIV negative
• No preexisting neuropathy ≥ grade 2
• No active or uncontrolled infection
• No other serious illness or medical condition
• No chronic alcohol abuse
• No known hypersensitivity to systemic liposomal formulations or compounds chemically related to OSI-7904L or oxaliplatin
• No prior psychiatric or neurologic condition that would preclude study compliance or giving informed consent

Expected Enrollment

A total of 3-25 patients will be accrued for this study.

Outcomes

Maximum tolerated dose and recommended dose for future trials as measured by CTC v3.0

Safety profile as measured by CTC v3.0
Response as measured by RECIST every 6 weeks (2 courses)
Pharmacodynamics as measured by drug concentration in the blood during course 1
Time to progression as measured by Kaplan Meier and RECIST every 6 weeks during treatment and then every 8 weeks

Outline

This is a nonrandomized, multicenter, open-label, dose-escalation study.

Patients receive oxaliplatin IV over 2 hours followed by OSI-7904L IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of OSI-7904L and oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. A maximum of 12 patients receive treatment at the MTD.

Patients are followed every 8 weeks.

Clamp AR, Schöffski P, Valle JW, et al.: A phase I and pharmacokinetic study of OSI-7904L, a liposomal thymidylate synthase inhibitor in combination with oxaliplatin in patients with advanced colorectal cancer. Cancer Chemother Pharmacol 61 (4): 579-85, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Patrick Schoffski, MD, MPH, Protocol chair(Contact information may not be current)		Ph: 49-511-532-4077 Email: patrick.schoffski@uz.kuleuven.be

Registry Information
Official Title		A Phase I Study of OSI-7904L In Combination With Oxaliplatin In Patients With Advanced Colo-Rectal Cancer
Trial Start Date		2004-02-20
Registered in ClinicalTrials.gov		NCT00081237
Date Submitted to PDQ		2004-02-27
Information Last Verified		2005-09-08

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