RATIONALE: ISIS 2503 may kill cancer cells by inhibiting a gene that promotes the
development and growth of cancer.
PURPOSE: Phase II trial to study the effectiveness of ISIS 2503 in treating patients who
have metastatic and/or locally recurrent colorectal cancer.
OBJECTIVES: I. Determine the response rate, duration of response, and time to progression in
patients with metastatic and/or locally recurrent adenocarcinoma of the colon or rectum
treated with ISIS 2503, an antisense inhibitor of H-ras. II. Determine the safety profile of
this regimen in these patients.
OUTLINE: This is a multicenter study. Patients receive ISIS 2503 IV continuously for 14
days. Courses repeat every 3 weeks in the absence of disease progression or unacceptable
PROJECTED ACCRUAL: A total of 14-25 patients will be accrued for this study within 1 year.
DISEASE CHARACTERISTICS: Histologically proven metastatic and/or locally recurrent
adenocarcinoma of the colon or rectum that is not expected to be cured with standard
therapy Patients who previously underwent definitive surgical resection and subsequently
develop metastatic disease should have diagnosis reconfirmed with new histologic or
cytologic specimen if: More than 5 years have elapsed since primary surgery OR Primary
tumor was stage I or II At least 1 measurable lesion (2 cm or more in widest diameter) by
CT or MRI scan No CNS metastases
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0 or 1 Life expectancy:
Not specified Hematopoietic: Absolute neutrophil count greater than 1,500/mm3 Platelet
count greater than 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL Renal:
Creatinine no greater than 1.5 mg/dl Other: Not pregnant or nursing Negative pregnancy
test Fertile patients must use effective contraception during and for 6 months after study
No underlying disease state associated with active bleeding No active infection requiring
therapy No second malignancy within the past 5 years except curatively treated
nonmelanomatous skin cancer
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior
chemotherapy for metastatic disease At least 6 months since prior adjuvant chemotherapy
with or without radiotherapy Endocrine therapy: Not specified Radiotherapy: Prior
radiotherapy to nonindicator lesion allowed and recovered See Chemotherapy Surgery: See
Disease Characteristics Other: No concurrent approved cancer therapy or other experimental