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
|ClinicalTrials.gov Identifier: NCT00541112|
Recruitment Status : Terminated (Toxicity and lack of efficacy)
First Posted : October 8, 2007
Last Update Posted : February 11, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer||Biological: cetuximab Drug: capecitabine Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy||Phase 2|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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).|
|Actual Study Start Date :||October 29, 2007|
|Actual Primary Completion Date :||January 29, 2010|
|Actual Study Completion Date :||January 29, 2010|
- Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI
- Preoperative clinical response
- Progression-free survival
- Overall survival
- Early toxicity before surgery
- Early toxicity due to surgery (mortality at 30 days, postoperative complications, surgical recovery)
- Late toxicity
- Late radiotherapy toxicity by CTC AE v. 3.0
- Objective response of measurable metastases by RECIST
- Sexual function
- Downstaging and downsizing of patients with operable disease
- Surgical complications
- Sphincter function
- Predictive biomarkers of response to cetuximab
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00541112
|Bordeaux, France, 33076|
|Centre de Lutte Contre le Cancer Georges-Francois Leclerc|
|Dijon, France, 21079|
|Centre Oscar Lambret|
|Lille, France, 59020|
|Centre Leon Berard|
|Lyon, France, 69373|
|Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle|
|Montpellier, France, 34298|
|Centre Antoine Lacassagne|
|Nice, France, 06189|
|Centre Hospitalier Lyon Sud|
|Pierre Benite, France, 69495|
|Centre Rene Huguenin|
|Saint Cloud, France, 92210|
|Centre Alexis Vautrin|
|Vandoeuvre-les-Nancy, France, 54511|
|Institut Gustave Roussy|
|Villejuif, France, F-94805|
|Principal Investigator:||David Azria, MD, PhD||Institut du Cancer de Montpellier - Val d'Aurelle|