Irinotecan Hydrochloride, Fluorouracil, and Leucovorin Calcium With or Without Zibotentan in Treating Patients With Metastatic Colorectal Cancer

• Status: Completed
• Trial end date: 2012-09-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, fluorouracil, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Zibotentan may be effective in treating metastatic colorectal cancer that has not responded to oxaliplatin. It is not yet known whether combination chemotherapy is more effective when given with or without zibotentan in treating metastatic colorectal cancer.

PURPOSE: This randomized phase II trial is studying giving irinotecan hydrochloride together with fluorouracil and leucovorin calcium to see how well it works when given with or without zibotentan in treating patients with metastatic colorectal cancer.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cardiff University
• Treatments: Calcium; Calcium, Dietary; Camptothecin; Endothelin Receptor Antagonists; Fluorouracil; Irinotecan; Leucovorin; Levoleucovorin

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal cancer

• Metastatic disease with no bone metastases

• Must have progressed within 6 months of adjuvant oxaliplatin-containing chemotherapy and have no significant ongoing toxicity (excluding grade 1 neurotoxicity)

• Measurable disease by RECIST criteria

• No known brain or leptomeningeal metastases

• Stable disease following surgical resection or radiosurgery of oligometastases allowed

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• Life expectancy ≥ 12 weeks

• Hemoglobin ≥ 9.0 g/dL (no prior transfusion) OR ≥ 10.0 g/dL (transfusion within past 4 weeks)

• Absolute neutrophil count ≥ 1.5 times 10^9/L

• Platelet count ≥ 100 times 10^9/L

• Total bilirubin < 1.5 times upper limit of normal (ULN)

• AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN with liver metastases)

• Creatinine clearance ≥ 50 mL/min

• Negative pregnancy test

• Not pregnant or nursing

• Fertile patients must use effective double-method contraception during and for 3 months (female) or 2 months (male) after completion of study treatment

• No active infection or serious concurrent medical condition

• No significant cardiovascular disease including any of the following:

• History of NYHA class II-IV congestive heart failure requiring therapy

• History of unstable angina pectoris or myocardial infarction within the past 6 months

• Severe valvular heart disease

• Ventricular arrhythmia requiring treatment

• Prolonged QTc interval > 470 msec

• No concurrent medical condition, that in the investigator's judgement, will substantially increase the risk associated with the patient's participation in the study, or potentially hamper compliance with the study protocol and follow-up schedule

• No psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or compliance with the study protocol

• No gastrointestinal disorders likely to interfere with absorption of the study drug (e.g., partial bowel obstruction or malabsorption)

• No known serological positivity for hepatitis B or hepatitis C

• No immunocompromised patients (e.g., no known serological positivity for HIV)

• No other prior or current malignant disease likely to interfere with protocol treatment or comparisons

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior zibotentan or irinotecan hydrochloride

• More than 4 weeks since prior chemotherapy, radiotherapy (except for palliative reasons), endocrine therapy, or immunotherapy

• No more than 1 prior course of chemotherapy for metastatic disease

• No prior extensive radiotherapy (i.e., likely to deplete bone marrow reserve)

• At least 4 weeks since prior major surgery and recovered

• Concurrent corticosteroids allowed provided the dose is stable for 4 weeks and not altered during the first 15 days of this study

• No concurrent warfarin

• Low molecular weight heparin allowed