Chemotherapy and Radiation Therapy Before Surgery Followed by Capecitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced Rectal Cancer
- Registration Number
- NCT00766155
- Lead Sponsor
- European Organisation for Research and Treatment of Cancer - EORTC
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy that uses a 3-dimensional image of the tumor to help focus thin beams of radiation directly on the tumor may kill more tumor cells and have fewer side effects. Giving chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether capecitabine is more effective with or without oxaliplatin in treating patients with rectal cancer.
PURPOSE: This randomized phase III trial is studying giving chemotherapy together with radiation therapy before surgery followed by capecitabine with or without oxaliplatin to see how well it works in treating patients with locally advanced rectal cancer.
- Detailed Description
OBJECTIVES:
Primary
* Investigate whether the addition of oxaliplatin to neoadjuvant chemoradiotherapy and adjuvant chemotherapy comprising capecitabine improves disease-free survival in patients with locally advanced rectal cancer.
Secondary
* Compare the overall survival of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy and adjuvant chemotherapy comprising capecitabine with versus without oxaliplatin.
* Determine the loco-regional failure and distant failure of patients treated with these regimens.
* Determine the pathological down-staging (ypT0-2N0) of patients treated with these regimens.
* Determine the pathological complete remission (yp T0N0) rate of patients treated with these regimens.
* Determine the tumor progression grade and histopathological R0 resection of patients treated with these regimens.
* Determine the sphincter preservation rate of patients treated with these regimens.
* Determine the perioperative complication rate of these regimens in these patients.
* Determine the toxicity of these regimens in these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to treating center, clinical T category (T1-3 vs T4), clinical nodal status (Nx vs NO vs N1-2), distance from the tumor to the anal verge (≤ 5 cm vs \> 5 cm) and method of locoregional staging (EUS+MRI vs EUS+CTscan vs MRI alone). Patients are randomized to 1 of 2 treatment arms.
* Arm I (control):
* Neoadjuvant therapy: Patients receive oral capecitabine twice daily on days 1-35. Patients also undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33 followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38.
* Adjuvant therapy: Beginning 4-8 weeks after surgery, patients receive oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm II (investigational):
* Neoadjuvant therapy: Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients also receive oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 prior to radiotherapy followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38.
* Adjuvant therapy: Beginning 4-8 weeks after surgery, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed every 3 months for 3 years, and then every 6 months for 2 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1094
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Arm I capecitabine Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients may receive additional chemoradiotherapy on days 36-38. Patients then undergo surgery. Beginning 4-8 weeks after surgery, patients receive capecitabine twice daily on day 1-15. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm II capecitabine Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients also receive oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 prior to radiotherapy followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38. Beginning 4-8 weeks later, patients receive oxaliplatin IV over 2 hours on day 1, and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm II oxaliplatin Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients also receive oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 prior to radiotherapy followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38. Beginning 4-8 weeks later, patients receive oxaliplatin IV over 2 hours on day 1, and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Disease-free survival
- Secondary Outcome Measures
Name Time Method Loco-regional failure, defined as local or regional recurrence, inoperable disease, or R1 or R2 resection Distant failure (i.e., distant metastasis) Overall survival within at least the first 5 years after treatment Histopathological R0 resection rate Toxicity according to CTCAE v.3.0 weekly during treatment, at 4-8 weeks after surgery, at therapy completion, and every 6 months for 5 years after therapy completion Pathological down-stage (ypT0, 2N0) rate Sphincter preservation rate Preoperative complication rate Pathological complete remission (ypT0N0) rate Tumor regression grade