A Phase I/II, Pharmacokinetic, and Biologic Correlative Study of G3139, NSC # 683428 (Phosphorothioate Antisense Oligonucleotide Directed to Bcl-2) and Irinotecan in Patients With Metastatic Colorectal Cancer
18 Years
N/A
Both
Colorectal Cancer
Trial Information
A Phase I/II, Pharmacokinetic, and Biologic Correlative Study of G3139, NSC # 683428 (Phosphorothioate Antisense Oligonucleotide Directed to Bcl-2) and Irinotecan in Patients With Metastatic Colorectal Cancer
OBJECTIVES: I. Determine the dose-limiting toxic effects and maximum tolerated dose of
augmerosen (G3139) administered in combination with irinotecan in patients with unresectable
metastatic or recurrent colorectal cancer. II. Determine the quantitative and qualitative
toxicity of this drug combination in this patient population. III. Assess the plasma
pharmacokinetics of this combination in these patients. IV. Document the antitumor activity
of this drug combination in these patients in a phase II study. V. Determine the relevant
biologic endpoints of treatment in tumor biopsies prior to and after therapy with G3139 at
two dose levels and assess the pharmacokinetic and pharmacodynamic correlations.
OUTLINE: This is a dose-escalation, multicenter study. Patients receive augmerosen (G3139)
IV continuously on days 1-7 and irinotecan IV over 90 minutes on day 6. Treatment continues
every 21 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6
patients receive escalating doses of G3139 and irinotecan until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose-limiting toxicity. Once the MTD is determined, additional patients are
accrued to receive treatment with G3139 and irinotecan at the recommended phase II dose.
Patients are followed every 30 days until toxicity resolves.
PROJECTED ACCRUAL: A maximum of 18 patients will be accrued for the phase I portion of this
study. A maximum of 55 patients will be accrued for the phase II portion of this study.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed unresectable metastatic
or recurrent adenocarcinoma of the colon or rectum No brain metastases unless previously
treated, asymptomatic, on stable dose of decadron, and CT/MRI scan demonstrates no
evidence of edema Phase I: Measurable or evaluable disease Phase II: Measurable disease
Evidence of +1 bcl-2 expression on immunohistochemical staining in pathologic material
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At
least 12 weeks Hematopoietic: Platelet count at least 100,000/mm3 Hemoglobin at least 9.0
g/dL Absolute granulocyte count at least 1,500/mm3 Hepatic: Bilirubin no greater than 1.5
mg/dL AST/ALT no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver
metastases) PT/PTT normal Renal: Creatinine no greater than 1.5 mg/dL Other: Not pregnant
or nursing Negative pregnancy test Fertile patients must use effective contraception No
active infection No serious concurrent systemic disorders that would preclude study
treatment
PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: At
least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and
recovered No other concurrent chemotherapy Phase I: At least 4 weeks since prior
irinotecan and recovered Phase II: No more than 2 prior fluorouracil-based regimens for
metastatic disease No prior irinotecan Endocrine therapy: See Disease Characteristics No
concurrent anticancer hormonal therapy Radiotherapy: No concurrent radiotherapy Surgery:
See Disease Characteristics Other: No other concurrent experimental medications
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Anthony W. Tolcher, MD
Investigator Role:
Study Chair
Investigator Affiliation:
San Antonio Cancer Institute
Authority:
United States: Federal Food and Drug Administration
Study ID:
CDR0000067529
NCT ID:
NCT00004870
Start Date:
June 2000
Completion Date:
September 2002
Related Keywords:
- Colorectal Cancer
- stage IV colon cancer
- stage IV rectal cancer
- recurrent colon cancer
- recurrent rectal cancer
- adenocarcinoma of the colon
- adenocarcinoma of the rectum
- Colorectal Neoplasms
Name | Location |
|---|---|
| Ireland Cancer Center | Cleveland, Ohio 44106-5065 |
| Brooke Army Medical Center | Fort Sam Houston, Texas 78234-6200 |
| San Antonio Cancer Institute | San Antonio, Texas 78229-3264 |
