Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy and Oblimersen in Treating Patients With Advanced Colorectal Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 18 and over NCI SACI-IDD-02-23 NCI-5793, NCT00055822, 5793

Objectives

1. Determine the maximum tolerated dose of oblimersen when administered with oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced colorectal cancer.
2. Determine the quantitative and qualitative toxic effects of this regimen in these patients.
3. Determine the antitumor activity of this regimen in these patients.
4. Determine the plasma pharmacokinetics of oblimersen and oxaliplatin in patients treated with this regimen.
5. Determine relevant predictive biomarkers of response in patients treated with this regimen.

Entry 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

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

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/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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.

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.

Trial Contact Information

Trial Lead Organizations

San Antonio Cancer Institute

Anthony Tolcher, MD, Protocol chair		Ph: 210-616-5914

Registry Information
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
Trial Start Date		2002-10-25
Registered in ClinicalTrials.gov		NCT00055822 1
Date Submitted to PDQ		2003-01-17
Information Last Verified		2005-03-01
NCI Grant/Contract Number		U01-CA69853

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00055822