Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy in Treating Patients Who Are Undergoing Surgical Resection for Locally Advanced Rectal Cancer - Full Text View

Sponsor:	Radiation Therapy Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00081289

Purpose

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	Intervention	Phase
Colorectal Cancer	Drug: capecitabine Drug: irinotecan hydrochloride Drug: oxaliplatin Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	Randomized Phase II Trial Of Neoadjuvant Combined Modality Therapy For Locally Advanced Rectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Oxaliplatin Irinotecan U 101440E Irinotecan hydrochloride Capecitabine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pathologic complete response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to treatment failure and patterns of failure [ Designated as safety issue: No ]
Incidence of hematologic and non-hematologic grade 3-4 toxicity (preoperatively, postoperatively, and overall) [ Designated as safety issue: Yes ]
Tumor marker evaluation using preoperative tissue biopsy specimens and surgically resected tissue specimens [ Designated as safety issue: No ]
Quality of life as assessed after completion of chemoradiotherapy and adjuvant chemotherapy and then at 2 years [ Designated as safety issue: No ]

Estimated Enrollment:	141
Study Start Date:	March 2004
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I (neoadjuvant therapy) Patients receive neoadjuvant therapy comprising radiotherapy once daily, 5 days a week, for 6 weeks and concurrent oral capecitabine twice daily (5 days a week) for 6 weeks and irinotecan IV over 1 hour on days 1, 8, 22, and 29.	Drug: capecitabine Given orally Drug: irinotecan hydrochloride Given IV Radiation: radiation therapy Given once daily 5 days a week for 6 weeks
Experimental: Arm II (neoadjuvant therapy) Patients receive neoadjuvant therapy comprising radiotherapy and capecitabine as in arm I and oxaliplatin IV over 2 hours on days 1, 8, 15, 22, and 29.	Drug: capecitabine Given orally Drug: oxaliplatin Given IV Radiation: radiation therapy Given once daily 5 days a week for 6 weeks

Detailed Description:

OBJECTIVES:

Compare 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.
Compare the time to treatment failure and patterns of failure in patients treated with these regimens.
Compare the incidence of hematologic and non-hematologic grade 3-4 toxicity (preoperatively, postoperatively, and overall) in patients treated with these regimens.
Compare 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: Patients receive neoadjuvant therapy comprising radiotherapy once daily, 5 days a week, for 6 weeks and concurrent oral capecitabine twice 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: Patients receive neoadjuvant therapy comprising radiotherapy and capecitabine as in arm I 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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 < 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, 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00081289

Locations

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

Principal Investigator:

Neal J. Meropol, MD

Fox Chase Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Wong SJ, Winter K, Meropol NJ, Anne PR, Kachnic L, Rashid A, Watson JC, Mitchell E, Pollock J, Lee RJ, Haddock M, Erickson BA, Willett CG. Radiation Therapy Oncology Group 0247: A Randomized Phase II Study of Neoadjuvant Capecitabine and Irinotecan or Capecitabine and Oxaliplatin with Concurrent Radiotherapy for Patients with Locally Advanced Rectal Cancer. Int J Radiat Oncol Biol Phys. 2011 Jul 18; [Epub ahead of print]

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.

Responsible Party:	Walter John Curran, Jr, Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:	NCT00081289 History of Changes
Other Study ID Numbers:	CDR0000350136, RTOG-0247
Study First Received:	April 7, 2004
Last Updated:	July 29, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage III rectal cancer
adenocarcinoma of the rectum
stage II rectal cancer

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
Oxaliplatin
Irinotecan

Capecitabine
Camptothecin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on February 12, 2012