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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00613080
Recruitment Status : Completed
First Posted : February 12, 2008
Results First Posted : June 10, 2013
Last Update Posted : February 17, 2017
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

February 9, 2008
February 12, 2008
April 12, 2013
June 10, 2013
February 17, 2017
April 2008
January 2010   (Final data collection date for primary outcome measure)
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) ]
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.
Treatment-related gastrointestinal adverse events ≥ grade 2 as assessed by NCI CTCAE v. 3.0, occurring neoadjuvantly
Complete list of historical versions of study NCT00613080 on Archive Site
  • Intensity-modulated Radiotherapy (IMRT) Feasibility [ Time Frame: IMRT planning and dosing data is centrally reviewed for quality assurance ]
  • Pathologic Complete Response Rate [ Time Frame: After protocol surgery ]
  • 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 ]
  • 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 ]
  • Rate of Anterior Posterior Resections [ Time Frame: From registration to end of follow-up ]
  • Intensity-modulated Radiotherapy (IMRT) Feasibility
  • Pathologic Complete Response Rate
  • All treatment-related adverse events as assessed by NCI CTCAE v3.0
  • Patterns of failure (i.e., local, regional, and distant), including overall survival
  • Correlation of pre- and post-treatment serum cytokines with adverse events and efficacy
  • Rate of Anterior Posterior Resections
Not Provided
Not Provided
Combination Chemotherapy and Intensity-Modulated Radiation Therapy in Treating Patients Undergoing Surgery for Locally Advanced Rectal Cancer
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

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.



  • 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).


  • 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.

Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Colorectal Cancer
  • 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
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
  • Drug: oxaliplatin
  • Procedure: resection
  • Radiation: radiation therapy
  • Drug: FOLFOX
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2016
January 2010   (Final data collection date for primary outcome measure)


  • 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)


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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
Canada,   United States
Not Provided
Not Provided
Radiation Therapy Oncology Group
Radiation Therapy Oncology Group
  • National Cancer Institute (NCI)
  • NRG Oncology
Principal Investigator: Michael C. Garofalo, MD University of Maryland Greenebaum Cancer Center
Study Chair: Adam C. Berger, MD Sidney Kimmel Cancer Center at Thomas Jefferson University
Study Chair: Johanna Bendell, MD Duke Cancer Institute
Radiation Therapy Oncology Group
December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP