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.

Condition	Treatment or Intervention	Phase
Colon Cancer Rectal Cancer	Drug: fluorouracil  Drug: leucovorin calcium  Drug: oblimersen  Drug: oxaliplatin  Procedure: antisense therapy  Procedure: chemosensitization/potentiation  Procedure: chemotherapy	Phase I Phase II

Further Study Details: 

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.

• 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Texas
      San Antonio Cancer Institute, San Antonio,  Texas,  78229-3264,  United States

Study chairs or principal investigators

Anthony W. Tolcher, MD,  Study Chair,  San Antonio Cancer Institute   

Study ID Numbers:  CDR0000271308; SACI-IDD-02-23; NCI-5793; NCT00055822
Record last reviewed:  March 2005
Last Updated:  March 10, 2005
Record first received:  March 6, 2003
ClinicalTrials.gov Identifier:  NCT00055822
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08