Combination Chemotherapy in Treating Patients With Advanced or Metastatic Colorectal Cancer

A Randomized Phase II Trial Of Capecitabine And Different Schedules Of Irinotecan As First Line Treatment For Advanced Or Metastatic Colorectal Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy in treating patients who have advanced or metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Irinotecan 70 mg/m2; Drug: Irinotecan 240 mg/m2

Detailed Description

OBJECTIVES:

• Compare the efficacy of different schedules of irinotecan in combination with capecitabine as first-line therapy, in terms of objective response rate, in patients with advanced or metastatic colorectal cancer.
• Compare the time to treatment failure, time to progression, and overall survival of patients treated with these regimens.
• Compare the safety profile, in terms of toxicity, of these regimens in these patients.
• Determine the quality of life in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (0 vs 1); disease symptoms, including pain, weight loss, loss of appetite, malaise, and fever of unknown origin (yes vs no); weight loss during the past 6 months (more than 5% vs 5% or less); and disease-free interval (more than 6 months vs 6 months or less). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive irinotecan IV over 1 hour on days 1, 8, 15, 22, and 29 and oral capecitabine twice daily on days 1-14 and 22-35.
• Arm II: Patients receive irinotecan IV over 1 hour on days 1 and 22 and oral capecitabine as in arm I.

Treatment in both arms repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, on day 1 of each course, and at the first visit after treatment failure.

Patients are followed every 12 weeks for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 28-74 patients (14-37 per treatment arm) will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, CH-3010
    • Inselspital, Bern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced or metastatic colorectal cancer

  • Unresectable disease

• At least 1 bidimensionally measurable lesion

  • At least 2 cm in perpendicular diameters
• No evidence of CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 to 75

Performance status:

• 0-1

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 3,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin normal
• SGOT/SGPT no greater than 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.25 times ULN

Cardiovascular:

• No clinically significant cardiac disease
• No congestive heart failure
• No New York Heart Association class III or IV heart disease
• No symptomatic coronary artery disease
• No uncontrolled cardiac arrhythmia
• No myocardial infarction within the past year

Gastrointestinal:

• No evidence of dysphagia
• No malabsorption or intestinal obstruction that would affect absorption or excretion of study drugs
• No chronic diarrhea

Other:

• No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer
• No psychiatric disability that would preclude study compliance
• No other significant medical condition
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for advanced or metastatic disease

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• At least 4 weeks since prior major surgery to the gastrointestinal tract

Other:

• No concurrent therapy for history of seizures or CNS disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; Irinotecan i.v. 70 mg/m2, day 1, 8, 15, 22, 29; Capecitabine p.o. 2 x 1000 mg/m2, d1-14, d22-35;	Drug: Irinotecan 70 mg/m2; Irinotecan i.v. 70 mg/m2, day 1, 8, 15, 22, 29
Active Comparator: Arm B; Irinotecan i.v. 240 mg/m2 day 1 and day 22; Capecitabine p.o. 2 x 1000 mg/m2, d1-14, d22-35;	Drug: Irinotecan 240 mg/m2; Irinotecan i.v. 240 mg/m2 day 1 and day 22

Collaborators and Investigators

• Sponsor: Swiss Group for Clinical Cancer Research
• Investigators: Study Chair: Markus M. Borner, MD, University Hospital Inselspital, Berne

Publications and helpful links

General Publications

• Borner MM, Bernhard J, Dietrich D, Popescu R, Wernli M, Saletti P, Rauch D, Herrmann R, Koeberle D, Honegger H, Brauchli P, Lanz D, Roth AD; Swiss Group for Clinical Cancer Research (SAKK), Berne, Switzerland. A randomized phase II trial of capecitabine and two different schedules of irinotecan in first-line treatment of metastatic colorectal cancer: efficacy, quality-of-life and toxicity. Ann Oncol. 2005 Feb;16(2):282-8. doi: 10.1093/annonc/mdi047.

Study record dates

Study Major Dates

• Study Start: February 1, 2001
• Primary Completion (Actual): May 1, 2002
• Study Completion (Actual): December 1, 2003

Study Registration Dates

• First Submitted: February 14, 2002
• First Submitted That Met QC Criteria: June 24, 2003
• First Posted (Estimate): June 25, 2003

Study Record Updates

• Last Update Posted (Estimate): May 15, 2012
• Last Update Submitted That Met QC Criteria: May 14, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; stage III colon cancer; stage III rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: SAKK 41/00; EU-20141