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

NCT01205711 | Completed Phase 2 DMC

• 8 other identifiers: CDR0000685062WCTU-FOLFERAEUDRACT-2009-012151-23ISRCTN-73199181CRUK-09/023WCTU-SPON-671-09EU-21071ZENECA-WCTU-FOLFERA
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Colorectal Cancer

Keywords

recurrent colon cancer; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

Secondary Outcomes (3)

• Tolerability (side effects) and feasibility of use (number of participants requiring dose delays or reductions and/or treatment withdrawal)

• Objective response rate as assessed by RECIST criteria

• Overall survival

Interventions

FOLFIRI regimen DRUG

fluorouracil DRUG

irinotecan hydrochloride DRUG

leucovorin calcium DRUG

zibotentan DRUG

laboratory biomarker analysis OTHER

pharmacogenomic studies OTHER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cardiff University: lead

Study Sites (4)

Leicester Royal Infirmary

Leicester, England, LE1 5WW, United Kingdom

Location

Centre for Cancer Research and Cell Biology at Queen's University Belfast

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

Wales Cancer Trials Unit

Cardiff, Wales, CF11 9LJ, United Kingdom

Location

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, CF14 2TL, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Fluorouracil; Irinotecan; Leucovorin; ZD4054; Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Anne Thomas, MD

  University Hospitals, Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: September 17, 2010
• First Posted: September 20, 2010
• Study Start: April 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: September 1, 2012
• Last Updated: July 8, 2014

Record last verified: 2014-07

Locations

GB (4)