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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

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

Principal Investigator

Anthony W. Tolcher, MD

Investigator Role:

Study Chair

Investigator Affiliation:

San Antonio Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000271308

NCT ID:

NCT00055822

Start Date:

October 2002

Completion Date:

October 2004

Related Keywords:

  • Colorectal Cancer
  • adenocarcinoma of the colon
  • recurrent colon cancer
  • stage III colon cancer
  • stage IV colon cancer
  • adenocarcinoma of the rectum
  • recurrent rectal cancer
  • stage III rectal cancer
  • stage IV rectal cancer
  • Colorectal Neoplasms

Name

Location
San Antonio Cancer Institute San Antonio, Texas  78229-3264