Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 9 of 125 for:    colon cancer AND Rectal | ( Map: New Jersey, United States )

Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy in Treating Patients Who Are Undergoing Surgical Resection 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.
 
ClinicalTrials.gov Identifier: NCT00081289
Recruitment Status : Completed
First Posted : April 8, 2004
Results First Posted : November 25, 2013
Last Update Posted : February 17, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Brief Summary:

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Chemoradiotherapy (combining chemotherapy with radiation therapy) before surgery may shrink the tumor so that it can be removed. Giving chemotherapy after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase II trial is studying two different regimens of neoadjuvant chemoradiotherapy and adjuvant chemotherapy and comparing how well they work in treating patients who are undergoing surgical resection for locally advanced rectal cancer.


Condition or disease Intervention/treatment Phase
Colorectal Cancer Radiation: Radiation Therapy Drug: Capecitabine 1650 mg/m^2/day Drug: Capecitabine 1200 mg/m^2/day Drug: Irinotecan Drug: Oxaliplatin Procedure: Surgery Drug: Folinic Acid Drug: Fluorouracil Phase 2

Detailed Description:

OBJECTIVES:

  • Evaluate the pathologic complete response rate in patients with locally advanced rectal cancer undergoing surgical resection treated with 2 different regimens of neoadjuvant chemoradiotherapy and adjuvant chemotherapy.
  • Evaluate the time to treatment failure and patterns of failure in patients treated with these regimens.
  • Evaluate the incidence of hematologic and non-hematologic grade 3-4 toxicity (preoperatively, postoperatively, and overall) in patients treated with these regimens.
  • Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinical stage of tumor (T3 vs T4). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Neoadjuvant chemoradiation with irinotecan: Patients receive neoadjuvant therapy comprising radiotherapy once daily, 5 days a week, for 6 weeks and concurrent oral capecitabine 1200 mg/m^2 daily (5 days a week) for 6 weeks and irinotecan IV over 1 hour on days 1, 8, 22, and 29.

Patients undergo surgical resection 4-8 weeks after completing radiotherapy.

Beginning 4-6 weeks after surgery, patients receive adjuvant chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 14 days for a total of 9 courses.

  • Arm II: Neoadjuvant chemoradiation with oxaliplatin: Patients receive neoadjuvant therapy comprising radiotherapy and capecitabine 1650 mg/m^2 daily as in arm I (except for capecitabine dose) and oxaliplatin IV over 2 hours on days 1, 8, 15, 22, and 29.

Patients undergo surgical resection 4-8 weeks after completing radiotherapy.

Beginning 4-6 weeks after surgery, patients receive adjuvant chemotherapy comprising oxaliplatin, leucovorin calcium, and fluorouracil as in Arm I adjuvant chemotherapy. Treatment repeats every 14 days for a total of 9 courses.

Quality of life is assessed at baseline, within 1 week after completion of radiotherapy, within 1 week after completion of adjuvant chemotherapy (12 months), and then at 24 months.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 141 patients (approximately 70 per treatment arm) will be accrued for this study within 2 years.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 146 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial Of Neoadjuvant Combined Modality Therapy For Locally Advanced Rectal Cancer
Study Start Date : March 2004
Actual Primary Completion Date : May 2011
Actual Study Completion Date : December 2016

Arm Intervention/treatment
Experimental: Neoadjuvant chemoradiation with irinotecan
Patients receive neoadjuvant therapy comprising 45 Gy (1.8 Gy/fx) + 5.4 Gy boost (1.8 Gy/fx) radiation therapy (RT), oral capecitabine 1200mg/m^2/day 5 days/week during RT, and irinotecan 50 mg/m^2 IV for 1 hour days 1, 8, 22, 29. Surgery 4-8 weeks after RT. Postoperative chemotherapy beginning Day 1 postoperatively for nine 14-day cycles(folinic acid 400 mg/m^2 over 2 hours Day 1; 5-fluorouracil bolus 400 mg/m^2 IV push Day 1 plus 2400 mg/m^2 IV continuous infusion over 46 hours, beginning Day 1; and oxaliplatin 85 mg/m^2 IV over 2 hours Day 1) .
Radiation: Radiation Therapy
Pelvic radiation therapy given once daily 5 days a week for 6 weeks, 45 Gy in 25 fractions + boost of 5.4 Gy in 3 fractions for a total dose of 50.4 Gy.

Drug: Capecitabine 1200 mg/m^2/day
600 mg/m^2 q12 hours(1200 mg/m^2/day) orally 5 days per week during radiotherapy.

Drug: Irinotecan
50mg/m^2 IV over 1 hour on days 1, 8, 22, and 29
Other Name: Irinotecan Hydrochloride

Procedure: Surgery
All patients will undergo surgery four to eight 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.

Drug: Folinic Acid
400 mg/m^2 IV over 2 hours Day 1 (postoperatively) ,every 14 days, for nine 14-day cycles.
Other Name: Leucovorin

Drug: Fluorouracil

5-fluorouracil bolus 400 mg/m^2 IV push Day 1 (postoperatively), every 14 days, for nine 14-day cycles.

5-fluorouracil infusion 2400 mg/m^2 IV continuous infusion over 46 hours, beginning day 1, every 14 days, for nine 14-day cycles.

Other Name: 5-FU

Drug: Oxaliplatin
85 mg/m^2 IV over 2 hours Day 1 (postoperatively), every 14 days, for nine 14-day cycles.

Experimental: Neoadjuvant chemoradiation with oxaplatin
Patients receive neoadjuvant therapy comprising 45 Gy (1.8 Gy/fx) + 5.4 Gy boost (1.8 Gy/fx) radiation therapy (RT), oral capecitabine 1650mg/m^2/day 5 days/week during RT, and oxaplatin 50 mg/m^2 IV for 2 hours days 1, 8, 22, 29. Surgery 4-8 weeks after RT. Postoperative chemotherapy beginning Day 1 postoperatively for nine 14-day cycles(folinic acid 400 mg/m^2 over 2 hours Day 1; 5-fluorouracil bolus 400 mg/m^2 IV push Day 1 plus 2400 mg/m^2 IV continuous infusion over 46 hours, beginning Day 1; and oxaliplatin 85 mg/m^2 IV over 2 hours Day 1) .
Radiation: Radiation Therapy
Pelvic radiation therapy given once daily 5 days a week for 6 weeks, 45 Gy in 25 fractions + boost of 5.4 Gy in 3 fractions for a total dose of 50.4 Gy.

Drug: Capecitabine 1650 mg/m^2/day
825 mg/m^2 q12 hours (1650 mg/m^2/day) orally 5 days per week during radiotherapy.

Drug: Oxaliplatin
50mg/m^2 IV over 2 hours on days 1, 8, 15, 22, and 29

Procedure: Surgery
All patients will undergo surgery four to eight 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.

Drug: Folinic Acid
400 mg/m^2 IV over 2 hours Day 1 (postoperatively) ,every 14 days, for nine 14-day cycles.
Other Name: Leucovorin

Drug: Fluorouracil

5-fluorouracil bolus 400 mg/m^2 IV push Day 1 (postoperatively), every 14 days, for nine 14-day cycles.

5-fluorouracil infusion 2400 mg/m^2 IV continuous infusion over 46 hours, beginning day 1, every 14 days, for nine 14-day cycles.

Other Name: 5-FU

Drug: Oxaliplatin
85 mg/m^2 IV over 2 hours Day 1 (postoperatively), every 14 days, for nine 14-day cycles.




Primary Outcome Measures :
  1. Pathologic Complete Response Rate [ Time Frame: After protocol surgery ]

    A pathologic complete response (pCR) was defined as no evidence of residual cancer histologically; disease progression or death before surgery was considered less than pCR (even without surgical specimen). All cases were reviewed by the study's surgical oncology co-chair for the determination of pCR.

    Each arm was first analyzed alone. If the arm had 9 or more pCRs in 48 evaluable pts, then the null hypothesis (H0) of 10% pCR rate would be rejected in favor of the alternative hypothesis of 25%, providing 90% power with a two-sided 10% type I error rate. If both arms reject H0, then statistical selection theory would be used to choose the arm for further study in a phase III trial. If only one arm has acceptable pCR rate, then that arm would be pursued in a phase III trial.



Secondary Outcome Measures :
  1. Time to Treatment Failure and Patterns of Failure [ Time Frame: From randomization to date of local failure, regional failure, distant failure, death or last follow-up. Analysis occurs after all patients have been potentially followed for 12 months. ]
  2. Incidence of Hematologic and Non-hematologic Grade 3-4 Toxicity (Preoperatively, Postoperatively, and Overall) [ Time Frame: Three time frames: start of treatment to surgery, surgery to end of follow-up, and combined. ]
  3. Tumor Marker Evaluation Using Preoperative Tissue Biopsy Specimens and Surgically Resected Tissue Specimens [ Time Frame: End of study ]
  4. Quality of Life as Assessed After Completion of Chemoradiotherapy and Adjuvant Chemotherapy and Then at 2 Years [ Time Frame: From randomization to 3 timepoints: 1) completion of chemoradiation, 2) completion of post-operative chemotherapy (approximately 1 year), and 3) two years ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of adenocarcinoma of the rectum

    • Clinical stage T3 or T4 disease by endorectal ultrasound or physical examination (for T4 lesions only)
    • Tumor originating at or below 12 cm from the anal verge
    • No extension of disease into the anal canal
  • No evidence of distant metastases
  • No synchronous primary colon carcinomas except T1 lesions
  • Potentially resectable en bloc disease

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3

Hepatic

  • AST (aspartate aminotransferase) < 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase < 2.5 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • No known uncontrolled coagulopathy

Renal

  • Creatinine clearance > 50 mL/min

Cardiovascular

  • No congestive heart failure
  • No symptomatic coronary artery disease
  • No uncontrolled cardiac arrhythmias
  • No myocardial infarction within the past year
  • No other clinically significant cardiac disease

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 30 days after completion of study treatment
  • No concurrent serious uncontrolled infection
  • No malabsorption syndrome
  • No lack of physical integrity of the upper gastrointestinal tract
  • No evidence of uncontrolled seizures, central nervous system (CNS) disorders, or psychiatric disability that, judged by the investigator, is clinically significant, precludes giving informed consent, or interferes with compliance of oral drug intake
  • No other malignancy within the past 5 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or ductal carcinoma in situ of the breast
  • No other serious uncontrolled medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent routine prophylactic filgrastim (G-CSF)

Chemotherapy

  • No prior anticancer chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy to the pelvis
  • No concurrent intensity-modulated radiotherapy

Surgery

  • More than 4 weeks since prior major surgery

Other

  • More than 4 weeks since prior participation in another clinical trial
  • No concurrent cimetidine
  • No concurrent sorivudine or brivudine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00081289


Locations
Layout table for location information
United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
United States, Florida
Baptist-South Miami Regional Cancer Program
Miami, Florida, United States, 33176
United States, Illinois
Ingalls Cancer Care Center at Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
United States, New Jersey
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
Marlton, New Jersey, United States, 08053
United States, Pennsylvania
Northeast Radiation Oncology Center
Dunmore, Pennsylvania, United States, 18512
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Neal J. Meropol, MD Fox Chase Cancer Center

Publications of Results:
Wong SJ, Moughan J, Meropol NJ, et al.: Efficacy endpoints of RTOG 0247: A randomized phase II study of neoadjuvant capecitabine (C) and irinotecan (I) or C and oxaliplatin (O) with concurrent radiation therapy (RT) for locally advanced rectal cancer. [Abstract] J Clin Oncol 29 (Suppl 15): A-3517, 2011.
Wong SJ, Winter K, Meropol NJ, et al.: RTOG 0247: A randomized phase II study of neoadjuvant capecitabine and irinotecan versus capecitabine and oxaliplatin with concurrent radiation therapy for locally advanced rectal cancer. [Abstract] J Clin Oncol 26 (Suppl 15): A-4021, 2008.

Layout table for additonal information
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00081289     History of Changes
Other Study ID Numbers: RTOG-0247
CDR0000350136
First Posted: April 8, 2004    Key Record Dates
Results First Posted: November 25, 2013
Last Update Posted: February 17, 2017
Last Verified: December 2016
Keywords provided by Radiation Therapy Oncology Group:
stage III rectal cancer
adenocarcinoma of the rectum
stage II rectal cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Rectal Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Leucovorin
Folic Acid
Capecitabine
Fluorouracil
Oxaliplatin
Irinotecan
Levoleucovorin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents