Orange, California 92868

  • Colorectal Cancer

Purpose:

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.


Study summary:

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.


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


Study is Available At:


Original ID:

ACOSOG-Z6041


NCT ID:

NCT00114231


Secondary ID:

ACOSOG-Z6041


Study Acronym:


Brief Title:

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


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Alliance for Clinical Trials in Oncology


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

90


Enrollment Type:

Actual


Overall Contact Information

Official Name:Julio Garcia-Aguilar, MD, PhD
Study Chair
City of Hope Comprehensive Cancer Center

Study Dates

Start Date:May 2006
Completion Date:December 2014
Completion Type:Actual
Primary Completion Date:December 2013
Primary Completion Type:Actual
Verification Date:February 2018
Last Changed Date:February 21, 2018
First Received Date:June 13, 2005
First Results Date:February 21, 2018

Study Outcomes

Outcome Type:Primary Outcome
Measure:3-Year Disease-free Survival
Time Frame:Up to 3 years
Safety Issues:False
Description: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.
Outcome Type:Secondary Outcome
Measure:R0 Resection Rate (Negative Margin Rate)
Time Frame:At time of surgery
Safety Issues:False
Description:The rate (percentage) of patients with negative resection margins after undergoing local excision is reported below.
Outcome Type:Secondary Outcome
Measure:Morbidity and Mortality Rate
Time Frame:Up to 30 days
Safety Issues:False
Description:Morbidity and mortality after neoadjuvant cheoradiotherapy and local excision.
Outcome Type:Secondary Outcome
Measure:Rate of Pathologic Complete Response of the Primary Tumor
Time Frame:Up to 5 years
Safety Issues:False
Description: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: PATHOLO
Outcome Type:Secondary Outcome
Measure:Local Recurrence Rate
Time Frame:Up to 5 years
Safety Issues:False
Description: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.

Study Interventions

Intervention Type:Drug
Name:capecitabine
Arm Name:Treatment (capecitabine, oxaliplatin, radiotherapy
Other Name:Given IV
Intervention Type:Drug
Name:oxaliplatin
Description:Given IV
Arm Name:Treatment (capecitabine, oxaliplatin, radiotherapy
Intervention Type:Procedure
Name:neoadjuvant therapy
Description:Undergo surgery
Arm Name:Treatment (capecitabine, oxaliplatin, radiotherapy
Other Name:therapeutic conventional surgery
Intervention Type:Radiation
Name:radiation therapy
Description:Undergo radiotherapy
Arm Name:Treatment (capecitabine, oxaliplatin, radiotherapy
Other Name:irradiation, radiotherapy, therapy, radiation

Study Arms

Study Arm Type:Experimental
Arm Name:Treatment (capecitabine, oxaliplatin, radiotherapy, surgery)
Description: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 a

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Alliance for Clinical Trials in Oncology
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
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.
PMID:17103255
Reference Type:Results Reference
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.
PMID:21755378
Reference Type:Results Reference
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.
PMID:26474521

Data Source: ClinicalTrials.gov

Date Processed: April 07, 2020

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


This study is not currently recruiting Study Participants. The form below is not enabled.