Combination Chemotherapy and Oblimersen in Treating Patients With Advanced Colorectal Cancer

Sponsor

The University of Texas Health Science Center at San Antonio (Other)

Overall Status

Completed

CT.gov ID

NCT00055822

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Biological: oblimersen sodium Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2002

Actual Primary Completion Date :

Oct 1, 2004

Actual Study Completion Date :

Oct 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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