Combination Chemotherapy and Intensity-Modulated Radiation Therapy in Treating Patients Undergoing Surgery for Locally Advanced Rectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00613080
First received: February 9, 2008
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: capecitabine
Drug: oxaliplatin
Procedure: resection
Radiation: radiation therapy
Drug: FOLFOX
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of Preoperative Chemoradiotherapy Utilizing Intensity Modulated Radiation Therapy (IMRT) in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • The Percentage of Patients Experiencing Treatment-related Gastrointestinal Adverse Events ≥ Grade 2 Per National Cancer Institute (NCI) Common Terminology Critereia for Adverse Events (CTCAE) v. 3.0, Occurring Preoperatively [ Time Frame: From start of treatment to surgery or ≤ 90 days from the Start of Concurrent Treatment (for patients not undergoing surgery) ] [ Designated as safety issue: Yes ]
    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:
  • Intensity-modulated Radiotherapy (IMRT) Feasibility [ Time Frame: IMRT planning and dosing data is centrally reviewed for quality assurance ] [ Designated as safety issue: No ]
  • Pathologic Complete Response Rate [ Time Frame: After protocol surgery ] [ Designated as safety issue: No ]
  • All Treatment-related Adverse Events Per NCI CTCAE v3.0 Preoperative, Postoperative, and Overall [ Time Frame: Three timeframes: Start of treatment to surgery, Surgery to 3 months after the completion of postoperative chemotherapy and Combined ] [ Designated as safety issue: Yes ]
  • Patterns of Failure (i.e., Local, Regional, and Distant), Including Overall Survival (Death Due to Any Cause) [ Time Frame: From registration to date of local failure, regional failure, distant failure, death or last follow-up ] [ Designated as safety issue: No ]
  • Rate of Anterior Posterior Resections [ Time Frame: From registration to end of follow-up ] [ Designated as safety issue: No ]

Enrollment: 79
Study Start Date: April 2008
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
IMRT + Chemotherapy , Resection, Postoperative Chemotherapy
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)
Drug: capecitabine
1650 mg/m^2/day orally 5 days/week during radiotherapy.
Drug: oxaliplatin
Other Name: 50 mg/m^2 IV over 2 hours weekly for five weeks starting on day 1 of radiotherapy.
Procedure: resection
All patients 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) is at the discretion of the surgeon.
Radiation: radiation therapy
Pelvic intensity modulated radiation therapy (IMRT): 45 Gy in 25 fx Three dimensional conformal radiation therapy (3D-CRT) boost: 5.4 Gy in 3 fx to total dose of 50.4 Gy in 28 fx
Drug: FOLFOX

Postoperative chemotherapy is administered to all patients who have a complete resection of rectal cancer with negative surgical margins and begins within 4-8 weeks following surgical resection, consisting of a total of 9 14-day cycles. Oxaliplatin 85 mg/m^2, IV over 2 hours, day 1.

Leucovorin 400 mg/m^2, IV over 2 hours, day 1. 5-fluorouracil bolus 400 mg/m^2, IV push, day 1. 5-fluorouracil infusion 2400 mg/m^2, IV continuous infusion over 46 hours, day 1.

Other Name: Oxaplatin, leucovorin, 5-fluorouracil

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Pathologically confirmed diagnosis of adenocarcinoma of the rectum by biopsy technique that does not completely excise the lesion (e.g., fine needle aspiration, core needle biopsy)

    • Located up to 12 cm from the anal verge with no extension of malignant disease into the anal canal
    • Clinically determined to be stage T3 or T4,N0-N2, and M0 tumor as determined by the following assessments:

      • Colonoscopy and biopsy within 56 days prior to registration
      • History/physical examination (including medication history screen for contraindications) within 56 days prior to registration
      • Contrast-enhanced imaging of the abdomen and pelvis either by CT, MRI, or PET-CT (whole body preferred) within 56 days prior to registration
      • Chest x-ray (or CT) of the chest within within 56 days prior to registration to exclude distant metastases (except for patients who have had whole body PET-CT)
      • Transrectal ultrasound (TRUS) within 56 days prior to registration required to establish tumor stage

        • TRUS not required if clinical exam, CT of the pelvis, and/or MRI demonstrates T4 lesion
  • No synchronous primary colon carcinoma
  • No evidence of distant metastases (M1)

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • Zubrod performance status 0-2
  • ANC (absolute neutrophil count) ≥ 1,800/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve hemoglobin ≥ 8.0 g/dL allowed)
  • AST (aspartate aminotransferase) < 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase < 2.5 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • Creatinine clearance > 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior invasive malignancy except nonmelanoma skin cancer unless disease free for a minimum of 3 years

Exclusion criteria:

  • Severe, active comorbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the past 12 months
    • Transmural myocardial infarction within the past 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within the past 30 days
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • AIDS
    • Evidence of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake
    • Known, existing uncontrolled coagulopathy, unless clinically stable on anticoagulation therapy for ≥ 2 weeks
    • Evidence of peripheral neuropathy ≥ grade 2
  • Prior allergic reaction to oxaliplatin or capecitabine
  • Lack of physical integrity of the gastrointestinal tract (i.e., severe Crohn disease that results in malabsorption; significant bowel resection that would make one concerned about the absorption of capecitabine) or malabsorption syndrome that would preclude feasibility of oral chemotherapy (i.e., capecitabine)
  • Prior systemic chemotherapy for colorectal cancer (prior chemotherapy allowed provided it was for a cancer other than colorectal cancer)
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
  • Major surgery within 28 days of study enrollment(other than diverting colostomy without tumor resection)
  • Participation in any investigational drug study within 28 days of study enrollment.
  • Concurrent cimetidine, amifostine, and/or depot Sandostatin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00613080

  Hide Study Locations
Locations
United States, Alabama
Providence Cancer Center at Providence Hospital
Mobile, Alabama, United States, 36608
United States, California
Auburn Radiation Oncology
Auburn, California, United States, 95603
Radiation Oncology Centers - Cameron Park
Cameron Park, California, United States, 95682
Mercy Cancer Center at Mercy San Juan Medical Center
Carmichael, California, United States, 95608
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
California Cancer Center - Woodward Park Office
Fresno, California, United States, 93720
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
Radiation Oncology Center - Roseville
Roseville, California, United States, 95661
Mercy General Hospital
Sacramento, California, United States, 95819
Radiological Associates of Sacramento Medical Group, Incorporated
Sacramento, California, United States, 95815
Veterans Affairs Medical Center - San Diego
San Diego, California, United States, 92161
Solano Radiation Oncology Center
Vacaville, California, United States, 95687
United States, Florida
Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
Boca Raton, Florida, United States, 33486
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
Baptist Cancer Institute - Jacksonville
Jacksonville, Florida, United States, 32207
Baptist-South Miami Regional Cancer Program
Miami, Florida, United States, 33176
Integrated Community Oncology Network - Orange Park
Orange Park, Florida, United States, 32073
Bay Medical
Panama City, Florida, United States, 32401
United States, Georgia
Piedmont Hospital
Atlanta, Georgia, United States, 30309
John B. Amos Cancer Center
Columbus, Georgia, United States, 31904
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
Savannah, Georgia, United States, 31403-3089
United States, Illinois
Cancer Institute at St. John's Hospital
Springfield, Illinois, United States, 62702
United States, Indiana
Saint John's Cancer Center at Saint John's Medical Center
Anderson, Indiana, United States, 46016
Center for Cancer Care at Goshen General Hospital
Goshen, Indiana, United States, 46526
St. Vincent Oncology Center
Indianapolis, Indiana, United States, 46260
Cancer Center at Ball Memorial Hospital
Muncie, Indiana, United States, 47303-3499
United States, Kansas
Menorah Medical Center
Overland Park, Kansas, United States, 66209
Saint Luke's Hospital - South
Overland Park, Kansas, United States, 66213
Shawnee Mission Medical Center
Shawnee Mission, Kansas, United States, 66204
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Boston University Cancer Research Center
Boston, Massachusetts, United States, 02118
Dana-Farber/Brigham and Women's Cancer Center
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Hudner Oncology Center at Saint Anne's Hospital - Fall River
Fall River, Massachusetts, United States, 02721
United States, Minnesota
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Fairview Southdale Hospital
Edina, Minnesota, United States, 55435
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, United States, 55432
Minnesota Oncology Hematology, PA - Maplewood
Maplewood, Minnesota, United States, 55109
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, United States, 55422-2900
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, United States, 55416
United Hospital
Saint Paul, Minnesota, United States, 55102
St. Francis Cancer Center at St. Francis Medical Center
Shakopee, Minnesota, United States, 55379
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, United States, 55125
United States, Mississippi
Regional Cancer Center at Singing River Hospital
Pascagoula, Mississippi, United States, 39581
United States, Missouri
Cancer Institute of Cape Girardeau, LLC
Cape Girardeau, Missouri, United States, 63703
North Kansas City Hospital
Kansas City, Missouri, United States, 64116
Truman Medical Center - Hospital Hill
Kansas City, Missouri, United States, 64108
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
St. Joseph Medical Center
Kansas City, Missouri, United States, 64114
Research Medical Center
Kansas City, Missouri, United States, 64132
Parvin Radiation Oncology
Kansas City, Missouri, United States, 64116
Saint Luke's Cancer Institute at Saint Luke's Hospital
Kansas City, Missouri, United States, 64111
Saint Luke's East - Lee's Summit
Lee's Summit, Missouri, United States, 64086
Liberty Hospital
Liberty, Missouri, United States, 64068
Heartland Regional Medical Center
Saint Joseph, Missouri, United States, 64506
Barnes-Jewish West County Hospital
Saint Louis, Missouri, United States, 63141
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. Peters
Saint Peters, Missouri, United States, 63376
CCOP - Cancer Research for the Ozarks
Springfield, Missouri, United States, 65802
Hulston Cancer Center at Cox Medical Center South
Springfield, Missouri, United States, 65807
United States, Nebraska
Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, Nevada
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
University Medical Center of Southern Nevada
Las Vegas, Nevada, United States, 89102
Renown Institute for Cancer at Renown Regional Medical Center
Reno, Nevada, United States, 89502
United States, New Hampshire
Kingsbury Center for Cancer Care at Cheshire Medical Center
Keene, New Hampshire, United States, 03431
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New Jersey
Monmouth Medical Center
Long Branch, New Jersey, United States, 07740-6395
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
Marlton, New Jersey, United States, 08053
J. Phillip Citta Regional Cancer Center at Community Medical Center
Toms River, New Jersey, United States, 08755
United States, New York
Maimonides Cancer Center at Maimonides Medical Center
Brooklyn, New York, United States, 11219
Monter Cancer Center of the North Shore-LIJ Health System
Lake Success, New York, United States, 11042
CCOP - North Shore University Hospital
Manhasset, New York, United States, 11030
Don Monti Comprehensive Cancer Center at North Shore University Hospital
Manhasset, New York, United States, 11030
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
United States, North Carolina
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
Wayne Radiation Oncology
Goldsboro, North Carolina, United States, 27534
United States, Ohio
Summa Center for Cancer Care at Akron City Hospital
Akron, Ohio, United States, 44309-2090
Barberton Citizens Hospital
Barberton, Ohio, United States, 44203
Charles M. Barrett Cancer Center at University Hospital
Cincinnati, Ohio, United States, 45267
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210-1240
Cancer Care Center, Incorporated
Salem, Ohio, United States, 44460
Precision Radiotherapy at University Pointe
West Chester, Ohio, United States, 45069
Cancer Treatment Center
Wooster, Ohio, United States, 44691
United States, Oklahoma
Integris Oncology Services
Oklahoma City, Oklahoma, United States, 73112
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Rosenfeld Cancer Center at Abington Memorial Hospital
Abington, Pennsylvania, United States, 19001
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, United States, 19010
Northeast Radiation Oncology Center
Dunmore, Pennsylvania, United States, 18512
Dale and Frances Hughes Cancer Center at Pocono Medical Center
East Stroudsburg, Pennsylvania, United States, 18301
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Riddle Memorial Hospital Cancer Center
Media, Pennsylvania, United States, 19063
Upper Delaware Valley Cancer Center
Milford, Pennsylvania, United States, 18337
Cancer Center of Paoli Memorial Hospital
Paoli, Pennsylvania, United States, 19301-1792
Frankford Hospital Cancer Center - Torresdale Campus
Philadelphia, Pennsylvania, United States, 19114
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
Philadelphia, Pennsylvania, United States, 19107-5541
CCOP - Main Line Health
Wynnewood, Pennsylvania, United States, 19096
Lankenau Cancer Center at Lankenau Hospital
Wynnewood, Pennsylvania, United States, 19096
United States, Rhode Island
Rhode Island Hospital Comprehensive Cancer Center
Providence, Rhode Island, United States, 02903
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
Kingsport, Tennessee, United States, 37662
United States, Utah
American Fork Hospital
American Fork, Utah, United States, 84003
Sandra L. Maxwell Cancer Center
Cedar City, Utah, United States, 84720
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
Murray, Utah, United States, 84157
Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
Ogden, Utah, United States, 84403
Utah Valley Regional Medical Center - Provo
Provo, Utah, United States, 84604
Dixie Regional Medical Center - East Campus
Saint George, Utah, United States, 84770
Utah Cancer Specialists at UCS Cancer Center
Salt Lake City, Utah, United States, 84106
LDS Hospital
Salt Lake City, Utah, United States, 84103
United States, Vermont
Norris Cotton Cancer Center - North
Saint Johnsbury, Vermont, United States, 05819
United States, Virginia
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22908
Southwest Virginia Regional Cancer Center at Wellmonth Health
Norton, Virginia, United States, 24273
United States, Wisconsin
Columbia Saint Mary's Hospital - Ozaukee
Mequon, Wisconsin, United States, 53097
Columbia-Saint Mary's Cancer Care Center
Milwaukee, Wisconsin, United States, 53211
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Principal Investigator: Michael C. Garofalo, MD University of Maryland Greenebaum Cancer Center
Study Chair: Adam C. Berger, MD Kimmel Cancer Center (KCC)
Study Chair: Johanna Bendell, MD Duke Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00613080     History of Changes
Other Study ID Numbers: RTOG-0822, CDR0000586277
Study First Received: February 9, 2008
Results First Received: April 12, 2013
Last Updated: June 11, 2013
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
stage III rectal cancer
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Fluorouracil
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014