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