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
Recruitment status was Recruiting
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.
Drug: leucovorin calcium
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
|Study Design:||Allocation: Non-Randomized
Primary Purpose: Treatment
|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).|
- Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI [ Designated as safety issue: No ]
- Preoperative clinical response [ Designated as safety issue: No ]
- Progression-free survival [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Early toxicity before surgery [ Designated as safety issue: Yes ]
- Early toxicity due to surgery (mortality at 30 days, postoperative complications, surgical recovery) [ Designated as safety issue: Yes ]
- Late toxicity [ Designated as safety issue: Yes ]
- Late radiotherapy toxicity by CTC AE v. 3.0 [ Designated as safety issue: Yes ]
- Objective response of measurable metastases by RECIST [ Designated as safety issue: No ]
- Sexual function [ Designated as safety issue: No ]
- Downstaging and downsizing of patients with operable disease [ Designated as safety issue: No ]
- Surgical complications [ Designated as safety issue: No ]
- Sphincter function [ Designated as safety issue: No ]
- Predictive biomarkers of response to cetuximab [ Designated as safety issue: No ]
|Study Start Date:||July 2007|
- 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).
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00541112
|Bordeaux, France, 33076|
|Contact: Marianne Fonck, MD 33-5-5633-3242|
|Centre de Lutte Contre le Cancer Georges-Francois Leclerc||Recruiting|
|Dijon, France, 21079|
|Contact: Philippe Maingon, MD 33-380-737-517 firstname.lastname@example.org|
|Centre Oscar Lambret||Recruiting|
|Lille, France, 59020|
|Contact: Xavier Mirabel 33-3-2029-5521|
|Centre Leon Berard||Recruiting|
|Lyon, France, 69373|
|Contact: Isabelle Martel Lafay, MD 33-4-7878-5166|
|Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle||Recruiting|
|Montpellier, France, 34298|
|Contact: David Azria, MD, PhD 33-4-6761-3132 David.Azria@valdorel.fnclcc.fr|
|Centre Antoine Lacassagne||Recruiting|
|Nice, France, 06189|
|Contact: Eric Francois 33-4-9203-1613|
|Centre Hospitalier Lyon Sud||Recruiting|
|Pierre Benite, France, 69495|
|Contact: Jean-Christophe Saurin 33-4-7886-1289|
|Centre Rene Huguenin||Recruiting|
|Saint Cloud, France, 92210|
|Contact: Frederique B. Cvitkovic, MD 33-1-4711-1515 email@example.com|
|Centre Alexis Vautrin||Recruiting|
|Vandoeuvre-les-Nancy, France, 54511|
|Contact: Thierry Conroy, MD 33-3-8359-8460|
|Institut Gustave Roussy||Recruiting|
|Villejuif, France, F-94805|
|Contact: Patrick Ezra, MD 33-1-4211-4125|
|Principal Investigator:||David Azria, MD, PhD||Centre Val d'Aurelle - Paul Lamarque|