Combination Chemotherapy and Intensity-Modulated Radiation Therapy in Treating Patients Undergoing Surgery for Locally Advanced Rectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Registration Number
- NCT00613080
- Lead Sponsor
- Radiation Therapy Oncology Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving these treatments 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 the side effects and how well giving combination chemotherapy together with intensity-modulated radiation therapy works in treating patients undergoing surgery for locally advanced rectal cancer.
- Detailed Description
OBJECTIVES:
Primary
* To determine whether the incidence of neoadjuvant acute gastrointestinal toxicity (grade ≥ 2) associated with neoadjuvant chemoradiotherapy is reduced by inverse-planned intensity-modulated radiotherapy (IMRT)-based radiation treatment when compared with conventionally delivered radiotherapy, as was utilized in the capecitabine and oxaliplatin arm of RTOG-0247 (NCT00081289).
Secondary
* To evaluate the feasibility of performing IMRT in a cooperative group setting for the treatment of rectal cancer.
* To estimate the incidence of all toxicity (hematologic and non-hematologic) associated with protocol treatment in the neoadjuvant period, the adjuvant period, and overall.
* To estimate the pathologic complete response rate following neoadjuvant IMRT-based chemoradiotherapy.
* To estimate the time to treatment failure and patterns of failure.
* To correlate pre- and post-treatment levels of serum cytokines with symptoms during and pathological outcomes following neoadjuvant chemoradiotherapy for rectal cancer.
* To evaluate the rate of abdominoperineal resections.
OUTLINE: This is a multicenter study.
* Chemoradiotherapy: Patients undergo inverse-planned intensity-modulated radiotherapy to the pelvis once daily, 5 days a week, for 5 weeks (total of 45 Gy) and a 3-dimensional conformal radiotherapy boost to gross disease once daily for 3 days (total of 45 Gy). Beginning on the first day of radiotherapy and continuing through completion of radiotherapy, patients receive oral capecitabine twice daily, 5 days a week, for 5 weeks and oxaliplatin IV over 2 hours on days 1, 8, 15, 22, 29.
* Surgery: Within 4-8 weeks after completion of chemoradiotherapy, patients undergo resection of the rectal tumor.
* Adjuvant chemotherapy: Beginning 4-8 weeks after surgery, patients with completely resected disease and negative surgical margins receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV bolus on day 1 and fluorouracil IV infusion continuously over 46 hours beginning on day 1 . Treatment repeats every 14 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months after the start of treatment for 2 years, every 6 months for years 3-5, and then annually thereafter.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 79
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description IMRT + Chemotherapy , Resection, Postoperative Chemotherapy radiation therapy Radiation therapy (intensity modulated radiation therapy \[IMRT\] + three dimensional conformal radiation therapy \[3D-CRT\]) + neoadjuvant chemotherapy (capecitabine and oxaliplatin) followed by resection and postoperative chemotherapy (FOLFOX) IMRT + Chemotherapy , Resection, Postoperative Chemotherapy FOLFOX Radiation therapy (intensity modulated radiation therapy \[IMRT\] + three dimensional conformal radiation therapy \[3D-CRT\]) + neoadjuvant chemotherapy (capecitabine and oxaliplatin) followed by resection and postoperative chemotherapy (FOLFOX) IMRT + Chemotherapy , Resection, Postoperative Chemotherapy resection Radiation therapy (intensity modulated radiation therapy \[IMRT\] + three dimensional conformal radiation therapy \[3D-CRT\]) + neoadjuvant chemotherapy (capecitabine and oxaliplatin) followed by resection and postoperative chemotherapy (FOLFOX) IMRT + Chemotherapy , Resection, Postoperative Chemotherapy capecitabine Radiation therapy (intensity modulated radiation therapy \[IMRT\] + three dimensional conformal radiation therapy \[3D-CRT\]) + neoadjuvant chemotherapy (capecitabine and oxaliplatin) followed by resection and postoperative chemotherapy (FOLFOX) IMRT + Chemotherapy , Resection, Postoperative Chemotherapy oxaliplatin Radiation therapy (intensity modulated radiation therapy \[IMRT\] + three dimensional conformal radiation therapy \[3D-CRT\]) + neoadjuvant chemotherapy (capecitabine and oxaliplatin) followed by resection and postoperative chemotherapy (FOLFOX)
- Primary Outcome Measures
Name Time Method The Percentage of Patients Experiencing Treatment-related Gastrointestinal Adverse Events ≥ Grade 2 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 3.0, Occurring Preoperatively From start of treatment to surgery or ≤ 90 days from the Start of Concurrent Treatment (for patients not undergoing surgery) The percentage of patients experiencing preoperative treatment-related gastrointestinal adverse events ≥ grade 2. If patient did not receive surgery, then such adverse events \<= 90 days from the start of concurrent treatment are included.
- Secondary Outcome Measures
Name Time Method Overall Survival: 4-year Rate From registration to four years Overall survival time is defined as time from registration to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
Number of Patients in Protocol Adherence Categories for Intensity-modulated Radiotherapy (IMRT) Planning Pretreatment Real-time quality assurance was performed remotely by the study chair or the radiation oncology co-chair prior to initiation of treatment for the first 40 cases. The final cases enrolled were reviewed within 3 months after accrual was completed. Review included evaluation of clinical target volume (CTV) and planning target volume (PTV), Organs at Risk (OARs), and treatment plan dosimetry.
Local-regional Failure: 4-year Rate From registration to four years Local failure is defined as: (1) any recurrence or surgery to the primary site after a complete response (CR) reported at surgery or reported after the end of protocol treatment; or (2) persistence \[failure at one day post study entry\], absence of CR after protocol treatment was completed and patient lived at least 90 days from the end of treatment. Regional failure is defined as: (1) any recurrence after a nodal CR reported at surgery or reported after the end of protocol treatment; or (2) persistence, absence of nodal CR after protocol treatment was completed and patient lived at least 90 days from the end of treatment. Local-regional failure time is defined as time from registration to local or regional failure, last known follow-up (censored), or death (competing risk). Local-regional failure rates are estimated by the cumulative incidence method.
Disease-free Survival: 4-year Rate From registration to four years Disease is defined as local-regional failure or distant failure. Distant failure is defined as the appearance of peritoneal seeding or distant metastases. Local-regional failure is defined as: (1) any recurrence or surgery to the primary site after a complete response (CR) / any recurrence after a nodal CR - reported at surgery or reported after the end of protocol treatment; or (2) persistence \[failure at one day post study entry\], absence of primary/nodal CR after protocol treatment was completed and patient lived at least 90 days from the end of treatment. Disease-free survival time is defined as time from registration to the date of disease, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method.
Number of Patients Who Underwent Abdominoperineal Resection Surgery occurred 4 to 8 weeks following the completion of radiation therapy, approximately 9-13 weeks from start of treatment. All patients were to undergo surgery 4 to 8 weeks following the completion of radiation therapy. The choice of procedure (abdominoperineal resection (APR), low anterior resection (LAR), or LAR/coloanal anastomosis) was at the discretion of the surgeon. If more than 28 patients received abdominoperineal resection, this would result in a conclusion of an excessive number of abdominoperineal resections.
Number of Patients With Pathologic Complete Response At the time of surgery, which is 4-8 weeks after radiation therapy, approximately 9-13 weeks from treatment start. Pathologic complete response is defined as no evidence of residual cancer histologically in the resection specimen.
Percentage of Patients With Grade 3 or Higher Treatment-related Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 From study registration to end of follow-up. Maximum follow-up at time of analysis was 5.2 years. Grade refers to the severity of the adverse event (AE). The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Adverse events were compiled in four different time periods: 1) Preoperative: Preoperatively or, if no surgery, then ≤ 90 days from the Start of Concurrent Treatment; 2) Postoperative#1: Postoperatively and ≤ 30 days from the Date of Surgery; 3) Postoperative#2: Postoperatively and ≤ 90 days from the End of Postoperative Chemotherapy; 4) Overall: From start of concurrent treatment to end of follow-up;
Distant Failure: 4-year Rate From registration to four years Distant failure is defined as the appearance of peritoneal seeding or distant metastases. Time to distant failure is defined as time from registration to the date of distant failure, last known follow-up (censored), or death (competing risk). Distant failure rates are estimated by the cumulative incidence method.
Trial Locations
- Locations (120)
Piedmont Hospital
🇺🇸Atlanta, Georgia, United States
Regional Cancer Center at Singing River Hospital
🇺🇸Pascagoula, Mississippi, United States
Auburn Radiation Oncology
🇺🇸Auburn, California, United States
Providence Cancer Center at Providence Hospital
🇺🇸Mobile, Alabama, United States
Mercy Cancer Center at Mercy San Juan Medical Center
🇺🇸Carmichael, California, United States
Radiation Oncology Centers - Cameron Park
🇺🇸Cameron Park, California, United States
Rebecca and John Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
California Cancer Center - Woodward Park Office
🇺🇸Fresno, California, United States
Radiation Oncology Center - Roseville
🇺🇸Roseville, California, United States
Solano Radiation Oncology Center
🇺🇸Vacaville, California, United States
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
🇺🇸Boca Raton, Florida, United States
University of Florida Shands Cancer Center
🇺🇸Gainesville, Florida, United States
Baptist Cancer Institute - Jacksonville
🇺🇸Jacksonville, Florida, United States
Integrated Community Oncology Network - Orange Park
🇺🇸Orange Park, Florida, United States
Bay Medical
🇺🇸Panama City, Florida, United States
John B. Amos Cancer Center
🇺🇸Columbus, Georgia, United States
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Cancer Institute at St. John's Hospital
🇺🇸Springfield, Illinois, United States
Center for Cancer Care at Goshen General Hospital
🇺🇸Goshen, Indiana, United States
Saint John's Cancer Center at Saint John's Medical Center
🇺🇸Anderson, Indiana, United States
Menorah Medical Center
🇺🇸Overland Park, Kansas, United States
Cancer Center at Ball Memorial Hospital
🇺🇸Muncie, Indiana, United States
Greenebaum Cancer Center at University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Hudner Oncology Center at Saint Anne's Hospital - Fall River
🇺🇸Fall River, Massachusetts, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸Fridley, Minnesota, United States
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸Robbinsdale, Minnesota, United States
Minnesota Oncology Hematology, PA - Maplewood
🇺🇸Maplewood, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
Park Nicollet Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
St. Francis Cancer Center at St. Francis Medical Center
🇺🇸Shakopee, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Minnesota Oncology Hematology, PA - Woodbury
🇺🇸Woodbury, Minnesota, United States
Cancer Institute of Cape Girardeau, LLC
🇺🇸Cape Girardeau, Missouri, United States
Truman Medical Center - Hospital Hill
🇺🇸Kansas City, Missouri, United States
Saint Luke's Cancer Institute at Saint Luke's Hospital
🇺🇸Kansas City, Missouri, United States
St. Joseph Medical Center
🇺🇸Kansas City, Missouri, United States
North Kansas City Hospital
🇺🇸Kansas City, Missouri, United States
Parvin Radiation Oncology
🇺🇸Kansas City, Missouri, United States
CCOP - Kansas City
🇺🇸Kansas City, Missouri, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
Saint Luke's East - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Liberty Hospital
🇺🇸Liberty, Missouri, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
Barnes-Jewish West County Hospital
🇺🇸Saint Louis, Missouri, United States
CCOP - Cancer Research for the Ozarks
🇺🇸Springfield, Missouri, United States
Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. Peters
🇺🇸Saint Peters, Missouri, United States
Hulston Cancer Center at Cox Medical Center South
🇺🇸Springfield, Missouri, United States
Renown Institute for Cancer at Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Kingsbury Center for Cancer Care at Cheshire Medical Center
🇺🇸Keene, New Hampshire, United States
Monmouth Medical Center
🇺🇸Long Branch, New Jersey, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
🇺🇸Marlton, New Jersey, United States
Maimonides Cancer Center at Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
Monter Cancer Center of the North Shore-LIJ Health System
🇺🇸Lake Success, New York, United States
CCOP - North Shore University Hospital
🇺🇸Manhasset, New York, United States
Don Monti Comprehensive Cancer Center at North Shore University Hospital
🇺🇸Manhasset, New York, United States
Wayne Memorial Hospital, Incorporated
🇺🇸Goldsboro, North Carolina, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Wayne Radiation Oncology
🇺🇸Goldsboro, North Carolina, United States
Summa Center for Cancer Care at Akron City Hospital
🇺🇸Akron, Ohio, United States
Barberton Citizens Hospital
🇺🇸Barberton, Ohio, United States
Precision Radiotherapy at University Pointe
🇺🇸West Chester, Ohio, United States
Cancer Care Center, Incorporated
🇺🇸Salem, Ohio, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Cancer Treatment Center
🇺🇸Wooster, Ohio, United States
Northeast Radiation Oncology Center
🇺🇸Dunmore, Pennsylvania, United States
Rosenfeld Cancer Center at Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
Bryn Mawr Hospital
🇺🇸Bryn Mawr, Pennsylvania, United States
Dale and Frances Hughes Cancer Center at Pocono Medical Center
🇺🇸East Stroudsburg, Pennsylvania, United States
Riddle Memorial Hospital Cancer Center
🇺🇸Media, Pennsylvania, United States
Upper Delaware Valley Cancer Center
🇺🇸Milford, Pennsylvania, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Cancer Center of Paoli Memorial Hospital
🇺🇸Paoli, Pennsylvania, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Lankenau Cancer Center at Lankenau Hospital
🇺🇸Wynnewood, Pennsylvania, United States
Frankford Hospital Cancer Center - Torresdale Campus
🇺🇸Philadelphia, Pennsylvania, United States
CCOP - Main Line Health
🇺🇸Wynnewood, Pennsylvania, United States
Rhode Island Hospital Comprehensive Cancer Center
🇺🇸Providence, Rhode Island, United States
Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
🇺🇸Kingsport, Tennessee, United States
Hollings Cancer Center at Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
American Fork Hospital
🇺🇸American Fork, Utah, United States
Sandra L. Maxwell Cancer Center
🇺🇸Cedar City, Utah, United States
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
🇺🇸Murray, Utah, United States
Utah Valley Regional Medical Center - Provo
🇺🇸Provo, Utah, United States
Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
🇺🇸Ogden, Utah, United States
Dixie Regional Medical Center - East Campus
🇺🇸Saint George, Utah, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Norris Cotton Cancer Center - North
🇺🇸Saint Johnsbury, Vermont, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Southwest Virginia Regional Cancer Center at Wellmonth Health
🇺🇸Norton, Virginia, United States
Columbia Saint Mary's Hospital - Ozaukee
🇺🇸Mequon, Wisconsin, United States
London Regional Cancer Program at London Health Sciences Centre
🇨🇦London, Ontario, Canada
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber/Brigham and Women's Cancer Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Boston University Cancer Research Center
🇺🇸Boston, Massachusetts, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
CCOP - Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Baptist-South Miami Regional Cancer Program
🇺🇸Miami, Florida, United States
St. Vincent Oncology Center
🇺🇸Indianapolis, Indiana, United States
Veterans Affairs Medical Center - San Diego
🇺🇸San Diego, California, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Charles M. Barrett Cancer Center at University Hospital
🇺🇸Cincinnati, Ohio, United States
Shawnee Mission Medical Center
🇺🇸Shawnee Mission, Kansas, United States
Saint Luke's Hospital - South
🇺🇸Overland Park, Kansas, United States
Oklahoma University Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
Integris Oncology Services
🇺🇸Oklahoma City, Oklahoma, United States
Utah Cancer Specialists at UCS Cancer Center
🇺🇸Salt Lake City, Utah, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Radiological Associates of Sacramento Medical Group, Incorporated
🇺🇸Sacramento, California, United States
Mercy General Hospital
🇺🇸Sacramento, California, United States
Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Columbia-Saint Mary's Cancer Care Center
🇺🇸Milwaukee, Wisconsin, United States
Medical College of Wisconsin Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
J. Phillip Citta Regional Cancer Center at Community Medical Center
🇺🇸Toms River, New Jersey, United States