Radiation Therapy, Chemotherapy, and Cetuximab Followed by Surgery, Chemotherapy, and Cetuximab in Treating Patients With Locally Advanced or Metastatic Rectal Cancer That Can Be Removed by Surgery

NCT ID: NCT00541112

Last Updated: 2020-02-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-29
• Study Completion Date: 2010-01-29

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as capecitabine, oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radiation therapy together with combination chemotherapy and cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy and cetuximab after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II clinical trial is studying how well giving radiation therapy together with chemotherapy and cetuximab followed by surgery, chemotherapy, and cetuximab works in treating patients with locally advanced or metastatic rectal cancer that can be removed by surgery.

Detailed Description

OBJECTIVES:

Primary

• Determine the complete remission rate at 6 months after neoadjuvant radiotherapy, capecitabine, and oxaliplatin (XELOX), and cetuximab followed by surgery, adjuvant FOLFOX 4, and cetuximab in patients with synchronous locally advanced or metastatic cancer of the rectum with resectable metastases (T3-4 Nx or T2 N+ M1).

Secondary

• Determine progression-free survival.
• Determine overall survival.
• Assess toxicities.
• Evaluate objective response in patients with measurable metastases.
• Determine the rate of local recurrence.
• Evaluate the downstaging and downsizing of patients with operable disease.
• Evaluate surgical complications in patients with operable disease.
• Evaluate biological markers predictive of response to cetuximab.

OUTLINE: This is a multicenter study.

• Neoadjuvant therapy: Patients undergo radiotherapy for 5 weeks and receive concurrent oral capecitabine twice daily on days 1-5 of each week and oxaliplatin IV over 2 hours on day 1 of each week (XELOX). Patients also receive cetuximab IV on day 1 of the first week and on days 1-7 of weeks 2-5.
• Surgery: At 6 weeks after completing chemoradiotherapy, patients with resectable disease undergo surgery comprising total mesorectal excision. Patients with progressive disease, nonresectable tumor, or who require R2 surgery are removed from the study.
• Adjuvant therapy: Patients who undergo surgery, with or without removal of metastases, receive FOLFOX 4, comprising oxaliplatin IV over 2 hours, fluorouracil IV over 46 hours, and leucovorin calcium IV on day 1, and cetuximab IV. Treatment repeats every 2 weeks for up to 6 courses (approximately 3 months). Patients who have not undergone prior surgical resection of metastases may have surgery to remove metastases after completing this second regimen of chemotherapy.

After completion of study therapy, patients are followed periodically for up to 5 years.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cetuximab

Intervention Type: BIOLOGICAL

capecitabine

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

adjuvant therapy

Intervention Type: PROCEDURE

conventional surgery

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• ECOG performance status 0-2
• WBC ≥ 4,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Creatinine ≤ 130 µmol/L
• Transaminases ≤ 5 times upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients of must use effective contraception

Exclusion Criteria

• Contraindication to therapy with capecitabine, oxaliplatin, cetuximab, and/or radiotherapy
• Impossible to perform translational analyses
• Uncontrolled severe illness
• Severe renal or hepatic insufficiency
• Cardiac insufficiency or symptomatic coronary disease
• Sensitive peripheral neuropathy
• Uncontrolled diabetes
• Other malignancy within the past 10 years except previously treated basal cell skin cancer or carcinoma in situ of the cervix
• Impossible to participate in study due to geographic, social, or psychiatric reasons
• Patients who are under supervision or incarcerated

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior anticancer chemotherapy or radiotherapy for this cancer
• No therapy with coumarin anticoagulants, phenytoin, sorivudine, brivudine, antacids, or allopurinol
• No concurrent participation in another therapeutic study or receiving another experimental drug

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Azria, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institut du Cancer de Montpellier - Val d'Aurelle

Locations

Institut Bergonie

Bordeaux, , France

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, , France

Centre Oscar Lambret

Lille, , France

Centre Leon Berard

Lyon, , France

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, , France

Centre Antoine Lacassagne

Nice, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Centre Rene Huguenin

Saint-Cloud, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

Other Identifiers

FRE-FNCLCC-ACCORD-14/0604

Identifier Type: OTHER

Identifier Source: secondary_id

EU-20759

Identifier Type: -

Identifier Source: secondary_id

2006-003336-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDR0000565937

Identifier Type: -

Identifier Source: org_study_id