ro 31-7453 in treating patients with recurrent or refractory metastatic colorectal cancer

Conditions: Colorectal Cancer

Summary: 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 cancer.

objectives: * 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 these regimens. * determine the pharmacokinetic profiles of ro 31-7453 and its major metabolites in these patients. * 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 year.

Eligibility criteria:
disease characteristics: * 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 setting * 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 patient characteristics: age: * 18 and over performance status: * karnofsky 70-100% life expectancy: * not specified hematopoietic: * 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 hepatic: * 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 present) renal: * creatinine no greater than 1.5 times uln cardiovascular: * no new york heart association class iii or iv congestive heart failure * no myocardial infarction within the past 6 months gastrointestinal: * no bowel obstruction * no active uncontrolled malabsorption syndrome other: * 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: biologic therapy: * see chemotherapy * at least 2 weeks since prior biologic therapy and recovered chemotherapy: * 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 cytotoxic chemotherapy * at least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered endocrine therapy: * not specified radiotherapy: * at least 3 weeks since prior radiotherapy and recovered surgery: * no prior total gastrectomy other: * no other concurrent investigational agents

Keywords: stage iv colon cancer stage iv rectal cancer recurrent colon cancer recurrent rectal cancer adenocarcinoma of the colon adenocarcinoma of the rectum