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

  Show 120 Study Locations
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:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Fluorouracil
Capecitabine
Oxaliplatin
Leucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 28, 2014