NCT00312000

Brief 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.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
820

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jan 2003

Typical duration for phase_3

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2003

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2006

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

April 5, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 7, 2006

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2006

Completed
Last Updated

September 8, 2008

Status Verified

September 1, 2008

Enrollment Period

3.1 years

First QC Date

April 5, 2006

Last Update Submit

September 5, 2008

Conditions

Advanced Colorectal Cancer

Keywords

colorectalcancercapecitabineirinotecanoxaliplatin

Outcome Measures

Primary Outcomes (1)

  • Overall survival

    study duration

Secondary Outcomes (4)

  • Tumour response

    study duration

  • Progression free survival

    study duration

  • Quality of life

    study duration

  • Toxicity profile

    study duration

Study Arms (2)

1Capecitabine-irinotecan

ACTIVE COMPARATOR

1st line- 2nd line (3rd line oxaliplatin plus capecitabine)

Drug: capecitabine-irinotecan

2capecitabine plus irinotecan

EXPERIMENTAL

1st line (2nd line oxaliplatin plus capecitabine)

Drug: capecitabine+irinotecan (1st line)

Interventions

capecitabine-irinotecanDRUG

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

1Capecitabine-irinotecan
capecitabine+irinotecan (1st line)DRUG

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

2capecitabine plus irinotecan

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (3)

  • Koopman M, Antonini NF, Douma J, Wals J, Honkoop AH, Erdkamp FL, de Jong RS, Rodenburg CJ, Vreugdenhil G, Akkermans-Vogelaar JM, Punt CJ. Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study. Ann Oncol. 2006 Oct;17(10):1523-8. doi: 10.1093/annonc/mdl179. Epub 2006 Jul 27.

    PMID: 16873425RESULT

  • Koopman M, Antonini NF, Douma J, Wals J, Honkoop AH, Erdkamp FL, de Jong RS, Rodenburg CJ, Vreugdenhil G, Loosveld OJ, van Bochove A, Sinnige HA, Creemers GM, Tesselaar ME, Slee PHTJ, Werter MJ, Mol L, Dalesio O, Punt CJ. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet. 2007 Jul 14;370(9582):135-142. doi: 10.1016/S0140-6736(07)61086-1.

    PMID: 17630036RESULT

  • van Kessel CS, Samim M, Koopman M, van den Bosch MA, Borel Rinkes IH, Punt CJ, van Hillegersberg R. Radiological heterogeneity in response to chemotherapy is associated with poor survival in patients with colorectal liver metastases. Eur J Cancer. 2013 Jul;49(11):2486-93. doi: 10.1016/j.ejca.2013.03.027. Epub 2013 May 18.

    PMID: 23692811DERIVED

Related Links

MeSH Terms

Conditions

Neoplasms

Interventions

capecitabine-irinotecan combination

Study Officials

  • C. J. A. Punt, Prof.Dr.

    University Medical Center St. Radboud, Nijmegen, The Netherlands

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

April 5, 2006

First Posted

April 7, 2006

Study Start

January 1, 2003

Primary Completion

February 1, 2006

Study Completion

December 1, 2006

Last Updated

September 8, 2008

Record last verified: 2008-09