RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die.
PURPOSE: Randomized phase II trial to compare the effectiveness of two different regimens of
Ro 31-7453 in treating patients who have recurrent or refractory metastatic colorectal
- Compare the objective disease rate of patients with recurrent or refractory metastatic
colorectal cancer treated with two dose schedules of Ro 31-7453.
- Compare the safety and tolerability of these regimens in these patients.
- Compare the response duration in patients treated with these regimens.
- Compare the time to progression and time to treatment failure in patients treated with
- Determine the pharmacokinetic profiles of Ro 31-7453 and its major metabolites in these
- Compare the overall survival of patients treated with these regimens.
OUTLINE: This is a randomized, open label, multicenter study. Patients are randomized to one
of two treatment arms.
- Arm I: Patients receive oral Ro 31-7453 twice daily on days 1-4. Treatment repeats
every 21 days in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive oral Ro 31-7453 twice daily on days 1-14. Treatment repeats
every 28 days in the absence of disease progression or unacceptable toxicity.
Patients are followed at 28 days and then every 3 months.
PROJECTED ACCRUAL: Approximately 160 patients (49 per treatment arm plus 61 additional
patients in the arm determined to be most effective) will be accrued for this study within 1
- Histologically confirmed metastatic adenocarcinoma of the colon or rectum
- Bidimensionally measurable disease
- At least 2.0 x 2.0 cm
- Failed prior fluoropyrimidine and irinotecan chemotherapy in adjuvant or metastatic
- Must have had disease progression while receiving chemotherapy OR
- If received fluorouracil with or without irinotecan in adjuvant setting, must
also have failed therapy with these agents in metastatic setting (unless
manifesting metastatic disease during adjuvant therapy)
- No known CNS metastases
- 18 and over
- Karnofsky 70-100%
- Not specified
- Hemoglobin at least 9 g/dL
- Absolute neutrophil count at least 1,500/mm^3
- WBC at least 3,000/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- AST/ALT no greater than 2.5 times ULN (5 times ULN if liver metastases present)
- Alkaline phosphatase no greater than 2.5 ULN (5 times ULN if bone or liver metastases
- Creatinine no greater than 1.5 times ULN
- No New York Heart Association class III or IV congestive heart failure
- No myocardial infarction within the past 6 months
- No bowel obstruction
- No active uncontrolled malabsorption syndrome
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infection
- No other prior malignancy within the past 5 years except carcinoma in situ of the
cervix or non-melanoma skin cancer
- No other active cancers, including stable disease on adjuvant therapy
- No other medical condition that would preclude study
PRIOR CONCURRENT THERAPY:
- See Chemotherapy
- At least 2 weeks since prior biologic therapy and recovered
- See Disease Characteristics
- No more than 2 prior cytotoxic chemotherapy regimens for metastatic disease
- Monoclonal antibody (MOAB) therapy and antiangiogenic agents not included as prior
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and
- Not specified
- At least 3 weeks since prior radiotherapy and recovered
- No prior total gastrectomy
- No other concurrent investigational agents