Neoadjuvant FOLFOX6 Chemotherapy With or Without Radiation in Rectal Cancer (FOWARC)
RATIONALE: Preoperative 5-Fu based chemoradiation has become standard treatment for stage 2/3 rectal cancer. However whether these patients, especially T3N0-1M0 patients, really need radiation for local control after total mesentery excision being applied in routine practice is still unknown. And whether new drugs adding in can achieve better local and distant control is worth investigating.
PURPOSE: This randomized phase II trial is studying 5Fu based radiation therapy or FOLFOX based radiation or FOLFOX alone, comparing them to see how well they work when given before surgery in treating patients with intermediate risk resectable rectal cancer. It is not yet known whether 5-Fu based or FOLFOX based radiation therapy or even FOLFOX alone is more effective in treating rectal cancer.
|Rectal Cancer||Drug: fluorouracil Drug: fluorouracil, oxaliplatin||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II/III Randomized Controlled Study of Neoadjuvant FOLFOX6 Treatment With or Without Radiation Compared to 5-Fu Based Chemoradiation in Treating Patients With Resectable Rectal Cancer|
- 3-year disease free survival [ Time Frame: 2 years ]Compare 3-year disease free survival in patients with resectable rectal cancer treated with either 5-Fu or FOLFOX based chemoradiotherapy or FOLFOX alone without radiation.
- pathologic complete response rate [ Time Frame: 1 years ]
- local recurrence rate [ Time Frame: 3 years ]
- overall survival [ Time Frame: 5 years ]
- sphincter-saving surgery rate [ Time Frame: 1 year ]
- R0 resection rate [ Time Frame: 1 year ]
- predictive biomarkers [ Time Frame: 3 year ]
- quality of life [ Time Frame: 3 year ]
|Study Start Date:||June 2010|
|Estimated Study Completion Date:||June 2020|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
Active Comparator: A: 5Fu with Radiation
Patients receive fluorouracil IV continuously and undergo radiotherapy once daily 5 days a week for 5-6 weeks.
Drug: fluorouracil Given IV continuously Radiation: radiation therapy Given 5 days a week for 5-6 weeks
Experimental: B: FOLFOX with radiation
Patients receive FOLFOX for 5 cycles and undergo radiotherapy as in arm I from the second cycle of FOLFOX
Drug: fluorouracil, oxaliplatin
Drug: fluorouracil Given IV continuously Drug: oxaliplatin Given IV Radiation: radiation therapy Given 5 days a week for 5-6 weeks
Experimental: C: FOLFOX alone
Patients receive FOLFOX for 4 cycles
Drug: fluorouracil, oxaliplatin
Drug: fluorouracil Given IV continuously Drug: oxaliplatin Given IV
Primary Compare the objective response rate and the rate of local-regional relapse in patients with resectable rectal cancer treated with either 5-Fu or FOLFOX based chemoradiotherapy or FOLFOX alone without radiation.
- Compare the rate of pathologic complete response in patients treated with these regimens.
- Compare the local recurrence rate
2.Determine the increase in the number of patients who are able to undergo sphincter-saving surgery after treatment with these regimens.
3.Correlate genetic patterns and the presence or absence of specific tissue biomarkers with response and prognosis in patients treated with these regimens.
4.Compare preoperative quality of life (QOL) of patients treated with oral capecitabine versus continuous infusion with fluorouracil. pelvic auto-nerve function 5.Determine the impact of oxaliplatin on neurotoxicity in patients treated with these regimens.
6.Compare the toxic effects of these regimens in these patients. 7.Compare the convenience of care in patients treated with these regimens. 8.Determine the impact of the type of surgical management on QOL at 1 year postoperatively in these patients.
OUTLINE: This is a randomized, multi-center study. Patients are stratified according to participating center, gender, clinical tumor stage (stage II vs. stage III), and surgical intent (sphincter saving vs. non-sphincter saving). Patients are randomized to 1 of 4 treatment arms.
- Arm A: Patients receive fluorouracil IV continuously and undergo radiotherapy once daily 5 days a week for 5-6 weeks.
- Arm B: Patients receive FOLFOX for 4 cycles and undergo radiotherapy as in arm I from the second cycle of FOLFOX.
- Arm C: Patients receive FOLFOX for 4 cycles Within 4-6 weeks after the completion of chemo radiotherapy, patients with responding or stable disease undergo surgery. Patients with progressive disease are treated at the discretion of the investigator and continue to be followed. Patients with progressive disease in arm III should received radiation.
Quality of life is assessed at baseline, at completion of chemo radiotherapy, and at 1 year after surgery.
After completion of study treatment, patients are followed every 3 months for 2 years, and then every 6 months for 3years.
PROJECTED ACCRUAL: A total of 495 patients will be accrued for this study within 5 years.
Eligibility Ages Eligible for Study: 18-75 Years old Genders Eligible for Study: Both Accepts Healthy Volunteers: No
Please refer to this study by its ClinicalTrials.gov identifier: NCT01211210
|Gastrointestinal Hospital, Sun Yatsen University|
|Guangzhou, Guangdong, China, 510655|
|Study Director:||Jianping Wang, MD||Sun Yatsen University|