Clinical trial NCT00114231: Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Stage I Rectal Cancer
Official title: A Phase II Trial of Chemoradiotherapy and Local Excision for uT2uN0 Rectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the rectum
stage I rectal cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-06-14
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: * 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

Primary outcomes:
measure: 3-Year Disease-free Survival
timeFrame: Up to 3 years
Secondary outcomes:
measure: R0 Resection Rate (Negative Margin Rate)
timeFrame: At time of surgery
measure: Morbidity and Mortality Rate
timeFrame: Up to 30 days
measure: Rate of Pathologic Complete Response of the Primary Tumor
timeFrame: Up to 5 years
measure: Local Recurrence Rate
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Concord
country: United States
facility: Cancer Care Center at John Muir Health - Concord Campus
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
state: California
city: Walnut Creek
country: United States
facility: John Muir/Mt. Diablo Comprehensive Cancer Center
state: California
city: Bridgeport
country: United States
facility: St. Vincent's Medical Center
state: Connecticut
city: Danbury
country: United States
facility: Praxair Cancer Center at Danbury Hospital
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Savannah
country: United States
facility: Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Savannah
country: United States
facility: Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: William N. Wishard Memorial Hospital
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Cancer Institute at Ochsner Clinic Foundation
state: Louisiana
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Grand Forks
country: United States
facility: Altru Cancer Center at Altru Hospital
state: North Dakota
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Oncology Services
state: Oklahoma
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Knight Cancer Institute at Oregon Health and Science University
state: Oregon
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Beaver
country: United States
facility: UPMC Cancer Center at Beaver Medical Center
state: Pennsylvania
city: Clairton
country: United States
facility: UPMC Cancer Center at Jefferson Regional Medical Center
state: Pennsylvania
city: Greensburg
country: United States
facility: UPMC Cancer Center - Arnold Palmer Pavilion
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Johnstown
country: United States
facility: UPMC Cancer Center at the John P. Murtha Pavilion
state: Pennsylvania
city: Moon
country: United States
facility: UPMC - Moon
state: Pennsylvania
city: Natrona Heights
country: United States
facility: UPMC Cancer Center - Natrona Heights
state: Pennsylvania
city: New Castle
country: United States
facility: Jameson Memorial Hospital - North Campus
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center at Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC - Shadyside
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at Magee-Womens Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at UPMC Presbyterian
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at UPMC St. Margaret
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at UPMC Passavant
state: Pennsylvania
city: Pittsburgh
country: United States
facility: St. Clair Memorial Hospital Cancer Center
state: Pennsylvania
city: Seneca
country: United States
facility: UPMC Cancer Center at UPMC Northwest
state: Pennsylvania
city: Washington
country: United States
facility: Washington Hospital Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: Newport News
country: United States
facility: Surgical Oncology Associates
state: Virginia
city: Spokane
country: United States
facility: Providence Cancer Center at Sacred Heart Medical Center
state: Washington
city: Spokane
country: United States
facility: Providence Cancer Center at Holy Family Hospital
state: Washington
city: Clarksburg
country: United States
facility: United Hospital Center
state: West Virginia
city: Huntington
country: United States
facility: Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: City of Hope Comprehensive Cancer Center
name: Julio Garcia-Aguilar, MD, PhD
role: STUDY_CHAIR
References:
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. doi: 10.1245/s10434-006-9213-7. Epub 2006 Nov 14. No abstract available.
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 Oncol. 2012 Feb;19(2):384-91. doi: 10.1245/s10434-011-1933-7. Epub 2011 Jul 14.
citation: 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.