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).
- 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.
Allocation: Non-Randomized, Primary Purpose: Treatment
Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI
David Azria, MD, PhD
Centre Val d'Aurelle - Paul Lamarque