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

Colorectal Cancer Clinical Trial

Official title:

Phase II Multicenter Study of the Impact of the Therapeutic Sequence of Radiochemotherapy (50 Gy + Capecitabine + Oxaliplatin + Cetuximab) Followed by Total Mesorectal Excision Surgery Then Post-surgery Chemotherapy (FOLFOX 4 + Cetuximab) in Synchronous Locally Advanced or Metastatic Cancers of the Rectum With Metastases Resectable From the Start (T3-4 Nx or T2 N+ M1).

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00541112
• Other study ID #: CDR0000565937
• Secondary ID: FRE-FNCLCC-ACCOR
• Status: Terminated
• Phase: Phase 2
• Start date: October 29, 2007
• Est. completion date: January 29, 2010

Study information

• Verified date: February 2020
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: January 29, 2010
• Est. primary completion date: January 29, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the rectum

• Locally advanced (T3-4 Nx) or metastatic (T2 N+ M1) synchronous disease

• Metastases must be resectable

• Primary tumor examined by endorectal echography and MRI

• Measurable disease by thoraco-abdomino-pelvic scanner

• Disease considered susceptible to treatment with radiotherapy and chemotherapy

• No diffuse metastases considered nonresectable

• No acute occlusion not caused by colostomy

PATIENT CHARACTERISTICS:

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Rectal Neoplasms

Intervention

Biological:
• cetuximab

Drug:
• capecitabine

• fluorouracil

• leucovorin calcium

• oxaliplatin

Procedure:
• adjuvant therapy

• conventional surgery

• neoadjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
France	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 Benite
France	Centre Rene Huguenin	Saint Cloud
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission at = 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI
Secondary	Preoperative clinical response
Secondary	Progression-free survival
Secondary	Overall survival
Secondary	Early toxicity before surgery
Secondary	Early toxicity due to surgery (mortality at 30 days, postoperative complications, surgical recovery)
Secondary	Late toxicity
Secondary	Late radiotherapy toxicity by CTC AE v. 3.0
Secondary	Objective response of measurable metastases by RECIST
Secondary	Sexual function
Secondary	Downstaging and downsizing of patients with operable disease
Secondary	Surgical complications
Secondary	Sphincter function
Secondary	Predictive biomarkers of response to cetuximab