Chemotherapy With or Without Surgery in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

A Randomized Trial of Initial Surgery in Advanced Asymptomatic Colorectal Cancer Patients Receiving Chemotherapy for Metastatic Disease

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether chemotherapy is more effective when given alone or together with surgery in treating patients with colorectal cancer.

PURPOSE: This randomized phase II/III trial is studying how well chemotherapy works and compares it with surgery followed by chemotherapy in treating patients with metastatic colorectal cancer that can not be removed by surgery.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: therapeutic conventional surgery; Procedure: adjuvant therapy; Procedure: quality-of-life assessment; Drug: systemic chemotherapy

Detailed Description

OBJECTIVES:

• To determine whether overall survival is improved in patients with asymptomatic, unresectable metastatic colorectal cancer treated with chemotherapy alone versus surgery followed by chemotherapy.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I (control arm): Patients receive systemic chemotherapy according to standard local practice. Patients who develop symptoms from their primary tumor receive treatment as required including surgery, if indicated.
• Arm II (experimental arm): Patients undergo surgery at the discretion of the surgeon. Beginning 8 weeks after completion of surgery, patients receive chemotherapy according to standard local practice.

Patients complete quality-of-life questionnaires (EQ-5D) at baseline and then periodically during and after completion of study treatment.

After completion of study treatment, patients are followed every 3 months.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, NW1 2BU
      • University College Hospital

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal cancer

  • Metastases which are unresectable at presentation
• No known unresectable primary tumor on CT/MRI scan

• Primary tumor does not require immediate or emergency intervention including surgery, radiotherapy, laser, or stenting

  • Patients who are treated with colonic stents are eligible
• No unequivocal extensive peritoneal metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Must be fit for systemic chemotherapy and surgery
• Hemoglobin > 10.0 g/dL
• WBC > 3.0 x 10^9/L
• Platelet count > 100 x 10^9/L
• Bilirubin < 25 μmol/L
• GFR > 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months (female) or up to 2 months (male) after completion of study therapy
• No history of malignant disease within the past 5 years except for nonmelanomatous skin cancer or carcinoma in situ of the cervix
• No serious medical co-morbidity (e.g., uncontrolled inflammatory bowel disease, uncontrolled angina, recent [within the past 6 months] myocardial infarction, or another serious medical condition) judged to compromise ability to tolerate chemotherapy and/or surgery

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Concurrent participation in a trial of chemotherapy, if eligible, allowed
• Concurrent short-course radiotherapy for operable rectal cancer allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Accrual rate in months 10 to 12 (phase II)
Overall survival for ≥ 2 years (phase III)

Secondary Outcome Measures

Outcome Measure
Quality of life (phase III)
Morbidity of surgery (phase II)
Percentage of patients who receive chemotherapy following surgery (must be over 80%) (phase II)
Morbidity of chemotherapy and surgery (phase III)
Economic evaluation (phase III)

Collaborators and Investigators

• Sponsor: University College London Hospitals
• Investigators: Principal Investigator: Austin Obichere, MD, University College London Hospitals

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: March 12, 2010
• First Submitted That Met QC Criteria: March 12, 2010
• First Posted (Estimate): March 15, 2010

Study Record Updates

• Last Update Posted (Estimate): August 26, 2013
• Last Update Submitted That Met QC Criteria: August 23, 2013
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon 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
• Other Study ID Numbers: CDR0000667364; UCL-08/0079; UCL-ISAAC; ISRCTN10963271; EU-21008; CRUK-C32436/A10431; EUDRACT-2008-005911-16; MREC-09/H1102/60; NCRI-UCL-08/0079