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

OBJECTIVES:

Primary

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

Secondary

• Determine the pharmacokinetic profile of this regimen in these patients.
• Determine the safety profile of this regimen in these patients.
• Determine the antitumor activity of this regimen in these patients.

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.

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

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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3

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

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