Sequential Versus Combination Chemotherapy in Advanced Colorectal Carcinoma

• Status: Completed
• Trial end date: 2006-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary objective:To assess the efficacy, defined as overall survival, of sequential versus combination chemotherapy for advanced colorectal cancer (CRC).

Methodology Open, randomised multicenter phase III study. Randomisation by centre will be centralized. 820 patiënts with histologically proven advanced CRC; not amenable to curative surgery. Measurable or evaluable disease. Age 18 years and above. WHO performance status 0-2.

Test products:

Arm A: First line: capecitabine capecitabine 1250 mg/m2 orally b.i.d. on day 1-14 (q3),until progression or unacceptable toxicity. Second line: irinotecan 350 mg/m2 IV infusion on day 1 (q3),until progression or unacceptable toxicity. Third line: oxaliplatin 130 mg/m2 IV infusion on day 1 and capecitabine 1000 mg/m2 orally b.i.d. on day 1-14 (q3). Arm B: First line: irinotecan 250 mg/m2 IV infusion in 30 minutes on day 1 and capecitabine 1000 mg/m2 orally b.i.d. on day 1-14 (q3), until progression or unacceptable toxicity. Second line: oxaliplatin 130 mg/m2 IV on day 1 and capecitabine 1000 mg/m2 orally b.i.d. on day 1-14 (q3), until progression or unacceptable toxicity.

Patients will be followed by CT-scan every 9 weeks for response while on treatment, or at any other moment when progression is suspected. After cessation of chemotherapy, patients will be followed every 3 months until death. Clinical and laboratory toxicity/symptomatology will be graded according to NCI common criteria.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dutch Colorectal Cancer Group
• Collaborators: Hoffmann-La Roche; Koningin Wilhelmina Fonds; Sanofi
• Treatments: Camptothecin; Capecitabine; Irinotecan; Oxaliplatin

Criteria

Inclusion Criteria:

• Histology and staging disease

• Histologically proven CRC; advanced disease, not amenable to curative surgery;

• Of Note: In case of a single metastasis, histological or cytological proof of colorectal carcinoma should be obtained prior to randomisation.

• Measurable or evaluable disease; Serum CEA as the only parameter for disease activity is not allowed.

• General conditions

• Written informed consent;

• Age 18 years and above;

• WHO performance status 0-2;

• Adequate bone marrow function(WBC > 3.0 x 109/L, platelets > 100 x 109/L, Hb > 6 mmol/L);

• Adequate hepatic function: total bilirubin < 1. 5 x upper normal limit, ASAT and ALAT < 3 x upper normal limits; in case of liver metastases < 5 x upper normal limits

• Adequate renal function: creatinin < 1. 5 x upper normal limits.

• Other - Expected adequacy of follow-up.

Exclusion Criteria:

• General conditions

• Pregnancy or lactation;

• Patients (M/F) with reproductive potential not implementing adequate contraceptives measures.

• Prior or current history

• Prior chemotherapy for advanced disease; prior adjuvant chemotherapy is allowed provided that the last administration was given > 6 months prior to randomisation.

• Serious concomitant diseases preventing the safe administration of chemotherapy or likely to interfere with the study assessments;

• Serious active infections;

• Inflammatory bowel disease or other diseases associated with chronic diarrhoea;

• Previous extensive irradiation of the pelvis or abdomen;

• Other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin.

• Concomitant treatments

• Concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation;

• Concurrent treatment with any other anti-cancer therapy.