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

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase

Completed

Phase 1

Conditions

Colorectal Cancer

Treatments

Drug: OSI-7904L

Drug: oxaliplatin

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00081237

OSI-EORTC-16033

EORTC-16033

Details and patient eligibility

About

RATIONALE: OSI-7904L may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining OSI-7904L with oxaliplatin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of OSI-7904L and oxaliplatin in treating patients with refractory or recurrent advanced colorectal cancer.

Full description

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.

Enrollment

15 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

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