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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00114231
First received: June 13, 2005
Last updated: August 3, 2015
Last verified: August 2015
  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.


Condition Intervention Phase
Colorectal Cancer
Drug: capecitabine
Drug: oxaliplatin
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Chemoradiotherapy and Local Excision for uT2uN0 Rectal Cancer

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of resectability as measured by the pathology report at surgery [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
  • morbidity and mortality rate [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
  • Rate of pathologic complete response of the primary tumor [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Local-failure-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Enrollment: 90
Study Start Date: May 2006
Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: capecitabine
Other Name: Given IV
Drug: oxaliplatin
Given IV
Procedure: neoadjuvant therapy
Undergo surgery
Other Name: therapeutic conventional surgery
Radiation: radiation therapy
Undergo radiotherapy
Other Name: irradiation, radiotherapy, therapy, radiation

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00114231

  Show 67 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Julio Garcia-Aguilar, MD, PhD Beckman Research Institute
  More Information

Additional Information:
Publications:
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00114231     History of Changes
Other Study ID Numbers: ACOSOG-Z6041, ACOSOG-Z6041, U10CA180821, U10CA076001, CDR0000433145
Study First Received: June 13, 2005
Last Updated: August 3, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
adenocarcinoma of the rectum
stage I rectal cancer

Additional relevant MeSH terms:
Capecitabine
Oxaliplatin
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 01, 2015