Oxaliplatin, Leucovorin, and Fluorouracil Before and After Radiation Therapy and Surgery in Treating Patients With Rectal Cancer That Can Be Removed by Surgery (COPERNICUS)
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, 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 chemotherapy 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.
PURPOSE: This phase II trial is studying giving oxaliplatin, leucovorin, and fluorouracil together, before and after radiation therapy and surgery in treating patients with rectal cancer that can be removed by surgery.
Drug: leucovorin calcium
Procedure: adjuvant therapy
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
Radiation: radiation therapy
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Stratified Phase II Study of Neoadjuvant Chemotherapy Given Before SCPRT as Treatment for Patients With MRI-Staged Operable Rectal Cancer at High Risk of Metastatic Relapse|
- Proportion of patients who commence neoadjuvant chemotherapy and radiotherapy and then undergo surgical resection [ Time Frame: Two years ]
- Feasibility in terms of achieved dose intensity for chemotherapy and radiotherapy [ Time Frame: Two years ]
- Safety in terms of NCI CTCAE v 4 toxicities up to 30 days postoperatively and late toxicity at 1 year after surgery [ Time Frame: Two years ]
- Complete response [ Time Frame: Two years ]
- Efficacy in terms of down-staging rectal cancer [ Time Frame: Two years ]
- Local recurrence-free, distant metastasis-free, and overall survival at 1 year after surgery [ Time Frame: Two years ]
|Study Start Date:||April 2012|
|Study Completion Date:||November 2015|
|Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Neo-adjuvant chemotherapy prior to short course pre-operative radiotherapy followed by adjuvant chemotherapy.
|Drug: Leucovorin Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: neoadjuvant therapy Procedure: therapeutic conventional surgery Radiation: radiation therapy|
- To assess the feasibility of introducing 8 weeks of neoadjuvant oxaliplatin and fluorouracil followed by radiotherapy and immediate surgical resection in patients with resectable adenocarcinoma of the rectum.
- Determine feasibility of achieving dose intensity for chemotherapy and radiotherapy in these patients.
- Determine the safety, in terms of NCI CTCAE version 4 toxicities, including postoperative complication rate (up to 30 days postoperatively), and late toxicity assessment at 1 year following surgery, in these patients.
- Determine how active is the neoadjuvant chemotherapy, in terms of down staging the rectal cancer, local recurrence-free, distant metastasis-free, and overall survival at 1 year following surgery in these patients.
Neoadjuvant therapy: Patients receive oxaliplatin and leucovorin (L-leucovorin or leucovorin calcium) IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Radiotherapy/Surgery: Beginning 1 week after completion of chemotherapy, patients undergo radiotherapy, followed by surgical resection of their primary tumor, within 7-14 days after completion of radiotherapy. Between 6-8 weeks following surgery, patients begin adjuvant therapy.
Adjuvant therapy: Patients receive oxaliplatin and leucovorin (L-leucovorin or leucovorin calcium) IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2. Treatment repeats every 2 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Blood and biopsy specimens are collected at baseline and periodically for translational research studies.
After completion of study therapy, patients are followed up periodically for 1 year.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01263171
|Coventry, England, United Kingdom, CV2 2DX|
|Leeds Cancer Centre at St. James's University Hospital|
|Leeds, England, United Kingdom, LS9 7TF|
|Manchester, England, United Kingdom, M20 4BX|
|Rosemere Cancer Centre at Royal Preston Hospital|
|Preston, England, United Kingdom, PR2 9HT|
|Royal Marsden - Surrey|
|Sutton, England, United Kingdom, SM2 5PT|
|Velindre Cancer Center at Velindre Hospital|
|Cardiff, Wales, United Kingdom, CF14 2TL|
|Glan Clwyd Hospital|
|Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ|
|Principal Investigator:||Simon Gollins, MD||Glan Clwyd Hospital|