Combination Chemotherapy and Oblimersen in Treating Patients With Advanced Colorectal Cancer

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00055822
• Other study ID #: CDR0000271308
• Secondary ID: U01CA069853P30CA
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 6, 2003
• Last updated: July 3, 2012
• Start date: October 2002
• Est. completion date: October 2004

Study information

• Verified date: July 2012
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: October 2004
• Est. primary completion date: October 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• oblimersen sodium

Drug:
• fluorouracil

• leucovorin calcium

• oxaliplatin

Locations

Country	Name	City	State
United States	San Antonio Cancer Institute	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,