Combination Chemotherapy and Oblimersen in Treating Patients With Advanced Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Oblimersen may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drugs. PURPOSE: Phase I/II trial to study the effectiveness of combining oxaliplatin, fluorouracil, and leucovorin with oblimersen in treating patients who have unresectable, metastatic, or recurrent colorectal cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of oblimersen when administered with oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced colorectal cancer. Determine the quantitative and qualitative toxic effects of this regimen in these patients. Determine the antitumor activity of this regimen in these patients. Determine the plasma pharmacokinetics of oblimersen and oxaliplatin in patients treated with this regimen. Determine relevant predictive biomarkers of response in patients treated with this regimen. OUTLINE: This is an open-label, phase I, dose-escalation study of oblimersen followed by a non-randomized, phase II study. Phase I: Patients receive oblimersen IV continuously on days 1-5 and 15-19; leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 6, 7, 20, and 21; and oxaliplatin IV over 2 hours on days 6 and 20. Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the highest dose at which no more than 1 of 6 patients experiences dose-limiting toxicity. Phase II: Up to 35 additional patients are treated as in phase I, with oblimersen at the MTD. In both phases, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed at 30 days. PROJECTED ACCRUAL: A total of 6-53 patients (6-18 patients for phase I and 12-35 patients for phase II) will be accrued for this study.

Official Title
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A Phase I/II Study of Oblimersen Sodium (G3139, Genasense) in Combination With Oxaliplatin, 5FU and Leucovorin (FOLFOX4) Regimen in Advanced Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: oblimersen sodium
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the colon or rectum Unresectable, metastatic, or recurrent disease Measurable or evaluable disease (phase I) Measurable disease (phase II) No known brain metastases Patients with previously treated brain metastases who are not currently receiving steroids and have a stable CT scan or MRI are eligible PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 OR Karnofsky 60-100% Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL Hepatic Bilirubin no greater than 1.5 mg/dL AST/ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present) INR no greater than 1.5 times ULN (unless currently receiving anticoagulant therapy) PT/PTT no greater than 1.5 times ULN (unless currently receiving anticoagulant therapy) Renal Creatinine normal OR Creatinine clearance at least 60 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of allergic reaction to compounds of similar chemical or biologic composition to fluorouracil or oxaliplatin No other concurrent uncontrolled medical condition that would preclude study participation No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No known history of degenerative facet disease during prior fluorouracil therapy No HIV-positive patients receiving combination antiretroviral therapy PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent epoetin alfa during course 1 No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF) No concurrent immunotherapy Chemotherapy At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No prior oxaliplatin No other concurrent chemotherapy Endocrine therapy See Disease Characteristics Radiotherapy At least 4 weeks since prior radiotherapy and recovered No concurrent radiotherapy Surgery Not specified Other No prior oblimersen No other concurrent investigational agents No other concurrent antitumor therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: oblimersen sodium|nan|
|Drug: fluorouracil|nan|
|Drug: leucovorin calcium|nan|
|Drug: oxaliplatin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent colon cancer, adenocarcinoma of the colon, stage III colon cancer, stage IV colon cancer, adenocarcinoma of the rectum, recurrent rectal cancer, stage III rectal cancer, stage IV rectal cancer