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

NCT00114231 | Completed Phase 2 Results DMC

• 4 other identifiers: ACOSOG-Z6041U10CA180821U10CA076001CDR0000433145
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 67

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

adenocarcinoma of the rectum; stage I rectal cancer

Outcome Measures

Primary Outcomes (1)

• 3-Year Disease-free Survival

  The primary endpoint was 3-year disease-free survival (DFS). Evidence of local recurrence, distant metastasis, or death from any cause within 3 years counted as events in the time-to-event Kaplan-Meier analysis of disease-free survival.

  Up to 3 years

Secondary Outcomes (4)

• R0 Resection Rate (Negative Margin Rate)

  At time of surgery

• Morbidity and Mortality Rate

  Up to 30 days

• Rate of Pathologic Complete Response of the Primary Tumor

  Up to 5 years

• Local Recurrence Rate

  Up to 5 years

Study Arms (1)

Treatment (capecitabine, oxaliplatin, radiotherapy, surgery)

EXPERIMENTAL

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.

Drug: capecitabine; Drug: oxaliplatin; Procedure: neoadjuvant therapy; Radiation: radiation therapy

Interventions

capecitabine DRUG

Also known as: Given IV

Treatment (capecitabine, oxaliplatin, radiotherapy, surgery)

oxaliplatin DRUG

Given IV

Treatment (capecitabine, oxaliplatin, radiotherapy, surgery)

neoadjuvant therapy PROCEDURE

Undergo surgery

Also known as: therapeutic conventional surgery

Treatment (capecitabine, oxaliplatin, radiotherapy, surgery)

radiation therapy RADIATION

Undergo radiotherapy

Also known as: irradiation, radiotherapy, therapy, radiation

Treatment (capecitabine, oxaliplatin, radiotherapy, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

* Patient must have an Eastern Cooperative Oncology Group (ECOG)/Zubrod status of =\< 2 * Patient must have histologically confirmed invasive adenocarcinoma of the rectum; Note: patients with rectal tumors suspicious for invasion also are eligible * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (67)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Cancer Care Center at John Muir Health - Concord Campus

Concord, California, 94524-4110, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

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

Orange, California, 92868, United States

Location

John Muir/Mt. Diablo Comprehensive Cancer Center

Walnut Creek, California, 94598, United States

Location

St. Vincent's Medical Center

Bridgeport, Connecticut, 06606, United States

Location

Praxair Cancer Center at Danbury Hospital

Danbury, Connecticut, 06810, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

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

Savannah, Georgia, 31403-3089, United States

Location

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

Savannah, Georgia, 31405, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, 46107, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

William N. Wishard Memorial Hospital

Indianapolis, Indiana, 46202, United States

Location

Reid Hospital & Health Care Services

Richmond, Indiana, 47374, United States

Location

Ochsner Cancer Institute at Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Altru Cancer Center at Altru Hospital

Grand Forks, North Dakota, 58201, United States

Location

Grandview Hospital

Dayton, Ohio, 45405, United States

Location

Good Samaritan Hospital

Dayton, Ohio, 45406, United States

Location

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Samaritan North Cancer Care Center

Dayton, Ohio, 45415, United States

Location

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, 45428, United States

Location

CCOP - Dayton

Dayton, Ohio, 45429, United States

Location

Blanchard Valley Medical Associates

Findlay, Ohio, 45840, United States

Location

Middletown Regional Hospital

Franklin, Ohio, 45005-1066, United States

Location

Wayne Hospital

Greenville, Ohio, 45331, United States

Location

Charles F. Kettering Memorial Hospital

Kettering, Ohio, 45429, United States

Location

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, 45373-1300, United States

Location

Clinton Memorial Hospital

Wilmington, Ohio, 45177, United States

Location

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, 45385, United States

Location

Integris Oncology Services

Oklahoma City, Oklahoma, 73112, United States

Location

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, 74136, United States

Location

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, 97213-2967, United States

Location

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest

Allentown, Pennsylvania, 18105, United States

Location

UPMC Cancer Center at Beaver Medical Center

Beaver, Pennsylvania, 15009, United States

Location

UPMC Cancer Center at Jefferson Regional Medical Center

Clairton, Pennsylvania, 15025, United States

Location

UPMC Cancer Center - Arnold Palmer Pavilion

Greensburg, Pennsylvania, 15601, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

UPMC Cancer Center at the John P. Murtha Pavilion

Johnstown, Pennsylvania, 15901, United States

Location

UPMC - Moon

Moon Township, Pennsylvania, 15108, United States

Location

UPMC Cancer Center - Natrona Heights

Natrona Heights, Pennsylvania, 15065, United States

Location

Jameson Memorial Hospital - North Campus

New Castle, Pennsylvania, 16105, United States

Location

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC - Shadyside

Pittsburgh, Pennsylvania, 15213-2582, United States

Location

UPMC Cancer Center at Magee-Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Cancer Center at UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Cancer Center at UPMC St. Margaret

Pittsburgh, Pennsylvania, 15215, United States

Location

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224-1791, United States

Location

UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

UPMC Cancer Center at UPMC Passavant

Pittsburgh, Pennsylvania, 15237, United States

Location

St. Clair Memorial Hospital Cancer Center

Pittsburgh, Pennsylvania, 15243, United States

Location

UPMC Cancer Center at UPMC Northwest

Seneca, Pennsylvania, 16346, United States

Location

Washington Hospital Cancer Center

Washington, Pennsylvania, 15301, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Methodist Hospital

Houston, Texas, 77030, United States

Location

Surgical Oncology Associates

Newport News, Virginia, 23606, United States

Location

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, 99204, United States

Location

Providence Cancer Center at Holy Family Hospital

Spokane, Washington, 99207, United States

Location

United Hospital Center

Clarksburg, West Virginia, 26301, United States

Location

Edwards Comprehensive Cancer Center at Cabell Huntington Hospital

Huntington, West Virginia, 25701, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

Related Publications (3)

• 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.

  PMID: 17103255 BACKGROUND

• 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.

  PMID: 21755378 RESULT

• 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.

  PMID: 26474521 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms

Interventions

Capecitabine; Oxaliplatin; Neoadjuvant Therapy; Radiotherapy; Radiation; Therapeutics

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Combined Modality Therapy; Physical Phenomena

Results Point of Contact

• Title: Julio Garcia-Aguilar, MD
• Organization: Memorial Sloan Kettering Cancer Center

garciaaj@mskcc.org

212-639-5506

Study Officials

• Julio Garcia-Aguilar, MD, PhD

  City of Hope Comprehensive Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2005
• First Posted: June 14, 2005
• Study Start: May 1, 2006
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2014
• Last Updated: March 29, 2018
• Results First Posted: March 29, 2018

Record last verified: 2018-02

Locations

US (67)