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

Colorectal Cancer Clinical Trial

Official title:

A Phase II Trial of Chemoradiotherapy and Local Excision for uT2uN0 Rectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00114231
• Other study ID #: ACOSOG-Z6041
• Secondary ID: ACOSOG-Z6041U10C
• Status: Completed
• Phase: Phase 2
• First received: June 13, 2005
• Last updated: February 21, 2018
• Start date: May 2006
• Est. completion date: December 2014

Study information

• Verified date: February 2018
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: December 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Rectal Neoplasms

Intervention

Drug:
• capecitabine

• oxaliplatin
Given IV

Procedure:
• neoadjuvant therapy
Undergo surgery

Radiation:
• radiation therapy
Undergo radiotherapy

Locations

Country	Name	City	State
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	UPMC Cancer Center at Beaver Medical Center	Beaver	Pennsylvania
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Vincent's Medical Center	Bridgeport	Connecticut
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	UPMC Cancer Center at Jefferson Regional Medical Center	Clairton	Pennsylvania
United States	United Hospital Center	Clarksburg	West Virginia
United States	Cancer Care Center at John Muir Health - Concord Campus	Concord	California
United States	Praxair Cancer Center at Danbury Hospital	Danbury	Connecticut
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	UPMC Cancer Center - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Wayne Hospital	Greenville	Ohio
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	William N. Wishard Memorial Hospital	Indianapolis	Indiana
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	UPMC Cancer Center at the John P. Murtha Pavilion	Johnstown	Pennsylvania
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	UPMC - Moon	Moon	Pennsylvania
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	UPMC Cancer Center - Natrona Heights	Natrona Heights	Pennsylvania
United States	Jameson Memorial Hospital - North Campus	New Castle	Pennsylvania
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Surgical Oncology Associates	Newport News	Virginia
United States	Integris Oncology Services	Oklahoma City	Oklahoma
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	St. Clair Memorial Hospital Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC - Shadyside	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center at Magee-Womens Hospital	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center at UPMC Passavant	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center at UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center at UPMC St. Margaret	Pittsburgh	Pennsylvania
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Providence Cancer Center at Holy Family Hospital	Spokane	Washington
United States	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington
United States	Tampa General Hospital	Tampa	Florida
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	John Muir/Mt. Diablo Comprehensive Cancer Center	Walnut Creek	California
United States	Washington Hospital Cancer Center	Washington	Pennsylvania
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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 — View Citation

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 — View Citation

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. Epub 2006 Nov 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	R0 Resection Rate (Negative Margin Rate)	The rate (percentage) of patients with negative resection margins after undergoing local excision is reported below.	At time of surgery
Secondary	Morbidity and Mortality Rate	Morbidity and mortality after neoadjuvant cheoradiotherapy and local excision.	Up to 30 days
Secondary	Rate of Pathologic Complete Response of the Primary Tumor	The rate (percentage) of patients with pathologic complete response (pCR) is reported below. Pathologic response will be determined by comparing tumor width and stage in the surgical specimen with the same parameters as determined by pre-CRT ERUS: PATHOLOGIC COMPLETE RESPONSE (pCR): no residual tumor.	Up to 5 years
Secondary	Local Recurrence Rate	The local recurrence rate (percentage) is defined as the percentage of patients who had local recurrence as initial sites of failure at the end of follow-up.	Up to 5 years