Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Stage I Rectal Cancer

NCT ID: NCT00114231

Last Updated: 2018-03-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-05-31

Study Completion Date

2014-12-31

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Oxaliplatin may make tumor cells more sensitive to radiation therapy. Giving capecitabine and oxaliplatin together with radiation therapy before surgery may shrink the tumor so it can be removed.

PURPOSE: This phase II trial is studying how well giving capecitabine and oxaliplatin together with radiation therapy works in treating patients who are undergoing surgery for stage I rectal cancer.

Detailed Description

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OBJECTIVES:

Primary

* Determine the 3-year disease-free survival rate in patients with stage I adenocarcinoma of the rectum treated with neoadjuvant chemoradiotherapy comprising capecitabine, oxaliplatin, and radiotherapy followed by local excision.

Secondary

* Determine the rate of resectability with negative resection margins in patients treated with this regimen.
* Determine the procedure-specific morbidity and mortality in patients treated with this regimen.
* Determine the rate of pathologic complete response of the primary tumor in patients treated with this regimen.
* Determine the impact of this regimen on anorectal function and quality of life in these patients.
* Determine the feasibility of using molecular studies to assess surgical resection margins and tumor response in patients treated with this regimen.
* Determine molecular markers associated with local tumor recurrence in patients treated with this regimen.

OUTLINE: This is a non-randomized, multicenter study.

Patients undergo high-dose external beam radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients also receive oral capecitabine twice daily on days 1-14 and 22-35 and oxaliplatin IV over 2 hours on days 1, 8, 22, and 29. Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo local excision of the tumor. Patients with T3 disease or positive resection margins after local excision undergo radical resection of the rectum and receive additional chemotherapy and/or radiotherapy at the discretion of the physician.

Quality of life is assessed at baseline and then 1 year after surgery.

After completion of study treatment, patients are followed at 1 month, every 4 months for 3 years, and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 102 patients will be accrued for this study within 2.8 years.

Conditions

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Colorectal Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (capecitabine, oxaliplatin, radiotherapy, surgery)

Patients undergo high-dose external beam radiotherapy once daily and receive capecitabine PO BID on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients also receive oxaliplatin IV over 2 hours on days 1, 8, 22, and 29.

Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo local excision of the tumor. Patients with T3 disease or positive resection margins after local excision undergo radical resection of the rectum and receive additional chemotherapy and/or radiotherapy at the discretion of the physician.

Group Type EXPERIMENTAL

capecitabine

Intervention Type DRUG

oxaliplatin

Intervention Type DRUG

Given IV

neoadjuvant therapy

Intervention Type PROCEDURE

Undergo surgery

radiation therapy

Intervention Type RADIATION

Undergo radiotherapy

Interventions

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capecitabine

Intervention Type DRUG

oxaliplatin

Given IV

Intervention Type DRUG

neoadjuvant therapy

Undergo surgery

Intervention Type PROCEDURE

radiation therapy

Undergo radiotherapy

Intervention Type RADIATION

Other Intervention Names

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Given IV therapeutic conventional surgery irradiation, radiotherapy, therapy, radiation

Eligibility Criteria

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Inclusion Criteria

* Distal border of the patient's tumor must be within 8 cm from the anal verge as measured on endoscopic exam
* Patients with tumors fixed to adjacent structures on digital exam are NOT eligible
* Patient must have an uT2uN0 tumor, as confirmed by endorectal ultrasound (ERUS) or endorectal coil magnetic resonance imaging (MRI) scan; patients with uT1, uT3, or uT4 tumors are NOT eligible; greatest diameter of tumor cannot exceed 4 cm
* Patients with positive perirectal nodes on ERUS examination are NOT eligible
* Patients with histologic evidence of metastatic invasion of inguinal lymph nodes are NOT eligible
* Patients with the following conditions are NOT allowed on study:

* Metastatic disease or other primaries (patient must have had chest X-ray/computed tomography \[CT\] and abdominal \& pelvic CT/MRI with IV contrast, as well as a colonoscopy)
* Previously documented history of familial adenomatous polyposis
* Previously documented history of hereditary non-polyposis colorectal cancer diagnosed clinically (Amsterdam II criteria) or by genetic testing
* History of inflammatory bowel disease
* History of prior radiation treatments to pelvis
* Clinically significant peripheral sensory or motor neuropathy (defined as symptomatic weakness, paresthesia or sensory alteration described to be interfering with function, interfering with activities of daily living, disabling or life-threatening)
* History of any clinically significant cardiac disease (i.e., class 3-4 congestive heart failure, symptomatic coronary artery disease, uncontrolled arrhythmia, and/or myocardial infarction within the last 6 months)
* History of uncontrolled seizures or clinically significant central nervous system disorders
* History of psychiatric conditions or diminished mental capacity that could compromise the giving of informed consent, or interfere with study compliance
* History of allergy and/or hypersensitivity to capecitabine and/or oxaliplatin
* History of difficulty or inability to take or absorb oral medications
* White blood cells (WBC) \>= 3000/mm\^3
* Absolute neutrophil count (ANC) \> 1,500/mm\^3
* Hemoglobin \> 9.5 mg/dl
* Platelet count \>= 100,000/mm\^3
* Total bilirubin =\< 3 mg/dl
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.0 times institutional upper limit of normal (ULN)
* Alkaline phosphatase =\< 2.0 times ULN
* Creatinine clearance (CLcr) \>= 50 ml/min by Cockroft-Gault equation
* Patients who have experienced a prior malignancy must have received potentially curative therapy for that malignancy, and must be cancer-free for at least five years from the date of initial diagnosis (exceptions: patients treated for non-melanoma skin carcinoma, or in-situ carcinomas)
* Patients of reproductive potential must agree to use an effective method of birth control when undergoing treatments with known or possible mutagenic or teratogenic effects; all female participants of childbearing potential must have a negative urine or serum pregnancy test within two weeks prior to study registration
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Julio Garcia-Aguilar, MD, PhD

Role: STUDY_CHAIR

City of Hope Comprehensive Cancer Center

Locations

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Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Site Status

Cancer Care Center at John Muir Health - Concord Campus

Concord, California, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

Orange, California, United States

Site Status

John Muir/Mt. Diablo Comprehensive Cancer Center

Walnut Creek, California, United States

Site Status

St. Vincent's Medical Center

Bridgeport, Connecticut, United States

Site Status

Praxair Cancer Center at Danbury Hospital

Danbury, Connecticut, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status

Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler

Savannah, Georgia, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

William N. Wishard Memorial Hospital

Indianapolis, Indiana, United States

Site Status

Reid Hospital & Health Care Services

Richmond, Indiana, United States

Site Status

Ochsner Cancer Institute at Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Altru Cancer Center at Altru Hospital

Grand Forks, North Dakota, United States

Site Status

Grandview Hospital

Dayton, Ohio, United States

Site Status

Good Samaritan Hospital

Dayton, Ohio, United States

Site Status

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, United States

Site Status

Samaritan North Cancer Care Center

Dayton, Ohio, United States

Site Status

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, United States

Site Status

CCOP - Dayton

Dayton, Ohio, United States

Site Status

Blanchard Valley Medical Associates

Findlay, Ohio, United States

Site Status

Middletown Regional Hospital

Franklin, Ohio, United States

Site Status

Wayne Hospital

Greenville, Ohio, United States

Site Status

Charles F. Kettering Memorial Hospital

Kettering, Ohio, United States

Site Status

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, United States

Site Status

Clinton Memorial Hospital

Wilmington, Ohio, United States

Site Status

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, United States

Site Status

Integris Oncology Services

Oklahoma City, Oklahoma, United States

Site Status

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, United States

Site Status

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States

Site Status

Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest

Allentown, Pennsylvania, United States

Site Status

UPMC Cancer Center at Beaver Medical Center

Beaver, Pennsylvania, United States

Site Status

UPMC Cancer Center at Jefferson Regional Medical Center

Clairton, Pennsylvania, United States

Site Status

UPMC Cancer Center - Arnold Palmer Pavilion

Greensburg, Pennsylvania, United States

Site Status

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

UPMC Cancer Center at the John P. Murtha Pavilion

Johnstown, Pennsylvania, United States

Site Status

UPMC - Moon

Moon Township, Pennsylvania, United States

Site Status

UPMC Cancer Center - Natrona Heights

Natrona Heights, Pennsylvania, United States

Site Status

Jameson Memorial Hospital - North Campus

New Castle, Pennsylvania, United States

Site Status

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC - Shadyside

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Cancer Center at Magee-Womens Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Cancer Center at UPMC Presbyterian

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Cancer Center at UPMC St. Margaret

Pittsburgh, Pennsylvania, United States

Site Status

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Cancer Center at UPMC Passavant

Pittsburgh, Pennsylvania, United States

Site Status

St. Clair Memorial Hospital Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Cancer Center at UPMC Northwest

Seneca, Pennsylvania, United States

Site Status

Washington Hospital Cancer Center

Washington, Pennsylvania, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Site Status

Methodist Hospital

Houston, Texas, United States

Site Status

Surgical Oncology Associates

Newport News, Virginia, United States

Site Status

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, United States

Site Status

Providence Cancer Center at Holy Family Hospital

Spokane, Washington, United States

Site Status

United Hospital Center

Clarksburg, West Virginia, United States

Site Status

Edwards Comprehensive Cancer Center at Cabell Huntington Hospital

Huntington, West Virginia, United States

Site Status

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Ota DM, Nelson H; ACOSOG Group Co-Chairs. Local excision of rectal cancer revisited: ACOSOG protocol Z6041. Ann Surg Oncol. 2007 Feb;14(2):271. doi: 10.1245/s10434-006-9213-7. Epub 2006 Nov 14. No abstract available.

Reference Type BACKGROUND
PMID: 17103255 (View on PubMed)

Garcia-Aguilar J, Shi Q, Thomas CR Jr, Chan E, Cataldo P, Marcet J, Medich D, Pigazzi A, Oommen S, Posner MC. A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol. 2012 Feb;19(2):384-91. doi: 10.1245/s10434-011-1933-7. Epub 2011 Jul 14.

Reference Type RESULT
PMID: 21755378 (View on PubMed)

Garcia-Aguilar J, Renfro LA, Chow OS, Shi Q, Carrero XW, Lynn PB, Thomas CR Jr, Chan E, Cataldo PA, Marcet JE, Medich DS, Johnson CS, Oommen SC, Wolff BG, Pigazzi A, McNevin SM, Pons RK, Bleday R. Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial. Lancet Oncol. 2015 Nov;16(15):1537-1546. doi: 10.1016/S1470-2045(15)00215-6. Epub 2015 Oct 22.

Reference Type RESULT
PMID: 26474521 (View on PubMed)

Other Identifiers

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ACOSOG-Z6041

Identifier Type: -

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA076001

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000433145

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACOSOG-Z6041

Identifier Type: -

Identifier Source: org_study_id

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