Sequential Versus Combination Chemotherapy in Advanced Colorectal Carcinoma

This study has been completed.
Sponsor:
Collaborators:
Koningin Wilhelmina Fonds
Sanofi
Hoffmann-La Roche
Information provided by:
Dutch Colorectal Cancer Group
ClinicalTrials.gov Identifier:
NCT00312000
First received: April 5, 2006
Last updated: September 5, 2008
Last verified: September 2008
  Purpose

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.


Condition Intervention Phase
Advanced Colorectal Cancer
Drug: capecitabine-irinotecan
Drug: capecitabine+irinotecan (1st line)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Study of Sequential Versus Combination Chemotherapy in Patients With Previously Untreated Advanced Colorectal Carcinoma

Resource links provided by NLM:


Further study details as provided by Dutch Colorectal Cancer Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: study duration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumour response [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: study duration ] [ Designated as safety issue: No ]
  • Toxicity profile [ Time Frame: study duration ] [ Designated as safety issue: Yes ]

Enrollment: 820
Study Start Date: January 2003
Study Completion Date: December 2006
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1Capecitabine-irinotecan
1st line- 2nd line (3rd line oxaliplatin plus capecitabine)
Drug: capecitabine-irinotecan
  1. st line capecitabine 1250 mg/m2 orally b.i.d. on day 1-14
  2. nd line q 3 w irinotecan 350 mg/m2 IV infusion on day 1
Experimental: 2capecitabine plus irinotecan
1st line (2nd line oxaliplatin plus capecitabine)
Drug: capecitabine+irinotecan (1st line)
q 3 w irinotecan 250 mg/m2 IV infusion in 30 minutes on day 1 2 hours after discontinuation of the infusion followed by capecitabine 1000 mg/m2 orally b.i.d. on day 1-14

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00312000

Sponsors and Collaborators
Dutch Colorectal Cancer Group
Koningin Wilhelmina Fonds
Sanofi
Hoffmann-La Roche
Investigators
Principal Investigator: C. J. A. Punt, Prof.Dr. University Medical Center St. Radboud, Nijmegen, The Netherlands
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: C.J.A. Punt, MD PhD, DCCG
ClinicalTrials.gov Identifier: NCT00312000     History of Changes
Other Study ID Numbers: CAIRO1
Study First Received: April 5, 2006
Last Updated: September 5, 2008
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Dutch Colorectal Cancer Group:
colorectal
cancer
capecitabine
irinotecan
oxaliplatin

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Irinotecan
Capecitabine
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 24, 2014