Overview

This trial is active, not recruiting.

Condition colorectal cancer
Treatments cetuximab, capecitabine, oxaliplatin, therapeutic surgical procedure, radiation therapy
Phase phase 2
Target EGFR
Sponsor Southwest Oncology Group
Collaborator National Cancer Institute (NCI)
Start date February 2009
End date July 2014
Trial size 80 participants
Trial identifier NCT00686166, S0713, U10CA032102

Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying the side effects and how well giving oxaliplatin, capecitabine, and cetuximab together with radiation therapy followed by surgery works in treating patients with stage II or stage III rectal cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Chemotherapy Cycle 1 (1 cycle is 35 days): Oxaliplatin, 50 mg/m^2, IV, Days 1,8,15,22,29 Cetuximab, 400 mg/m^2, IV, Day 1 Cetuximab, 250 mg/m^2, IV, Days 8,15,22,29 Capecitabine, 1650 mg/m^2/day, PO, Monday-Friday (Day 1-35) Chemotherapy+ Radiation Cycle 2: Oxaliplatin, 50 mg/m^2, IV, Days 50,57,71,78 Cetuximab, 250 mg/m^2, IV, Days 50,57,64,71,78 Capecitabine, 1650 mg/m^1, PO, Monday-Friday (Day 50-84) Radiation therapy: Planning target value 1: 4500 cGy (centigray) in 25 fractions; Planning target value 2 (stage T3 patients): Boost of 540 cGy in 3 fractions; Planning target value 2 (stage T4 patients): Boost of 900 cGy in 5 fractions. Therapeutic Surgical procedure: Resection
cetuximab IMG-C225
Chemotherapy cycle 1: Cetuximab, 400 mg/m^2, IV, Day 1; Cetuximab, 250 mg/m^2, IV, Days 8,15,22,29 Chemotherapy+ Radiation Cycle 2: Cetuximab, 250 mg/m^2, IV, Days 50,57,64,71,78
capecitabine Xeloda
Chemotherapy Cycle 1: Capecitabine, 1650 mg/m^2/day, PO, Monday-Friday (Day 1-35) Chemotherapy+ Radiation Cycle 2: Capecitabine, 1650 mg/m^1, PO, Monday-Friday (Day 50-84)
oxaliplatin Eloxatin
Chemotherapy Cycle 1: Oxaliplatin, 50 mg/m^2, IV, Days 1,8,15,22,29 Chemotherapy+ Radiation Cycle 2: Oxaliplatin, 50 mg/m^2, IV, Days 50,57,71,78
therapeutic surgical procedure Resection
Surgical resection
radiation therapy RT
IMRT (intensity-modulated radiation therapy)

Primary Outcomes

Measure
Pathologic complete response rate
time frame: 15-20 weeks from registration
Disease-free survival
time frame: 3 years
Frequency and severity of toxicities
time frame: Weekly through Week 12
Association between expression levels of genes involved in the DNA repair, EGFR, angiogenesis, and 5-FU pathway with pathologic complete response
time frame: 3 years
Intratumoral gene expression levels after completion of study treatment
time frame: 3 years
Data on genomic polymorphisms of these genes for correlation with clinical outcome and toxicity
time frame: 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Biopsy-proven primary adenocarcinoma of the rectum - Stage II or III disease - The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 cm of the anal verge by proctoscopic examination - No recurrent disease - Must have wild-type k-ras status - Measurable and/or nonmeasurable disease PATIENT CHARACTERISTICS: - Zubrod performance status 0-2 - Leukocyte count ≥ 3,000/mcL - Granulocyte count ≥ 1,500/mcL - Platelet count ≥ 100,000/mcL - Bilirubin ≤ 1.5 times upper limit of normal (ULN) - Alkaline phosphatase ≤ 2.5 times ULN - SGOT (serum glutamate oxaloacetate transaminase) or SGPT (serum glutamate pyruvate transaminase)≤ 2.5 times ULN - Creatinine clearance > 50 mL/min - No prior severe reaction to a monoclonal antibody - Willing to have specimens submitted - No peripheral neuropathy ≥ grade 2 - No known existing uncontrolled coagulopathy - No evidence of current high-grade obstruction - At least 2 weeks since prior diverting procedure - No history of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol treatment - No prior unanticipated severe reaction to fluoropyrimidine therapy or known sensitivity to fluorouracil or known DPD deficiency - No active inflammatory bowel disease, malabsorption syndrome, or inability to swallow that would impair the ingestion or absorption of capecitabine - No uncontrolled intercurrent illness - No ongoing or active infection - No symptomatic congestive heart failure or unstable angina pectoris - No cardiac arrhythmia or myocardial infarction within the past 12 months - Not pregnant or nursing - Fertile patients must use effective contraception - No prior malignancy allowed except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other cancer from which the patient has been disease-free for 5 years PRIOR CONCURRENT THERAPY: - Recovered from any recent major surgeries (e.g., coronary artery bypass graft, transurethral resection of prostate, or abdominal surgery) - No prior chemotherapy, radiotherapy, or targeted therapy for this tumor - More than 4 weeks since prior investigational agents - No concurrent anti-retroviral therapy for HIV

Additional Information

Official title A Phase II Study of Oxaliplatin, Capecitabine, Cetuximab and Radiation in Pre-Operative Therapy of Rectal Cancer
Description OBJECTIVES: - To assess the pathologic complete response rate for the combination of oxaliplatin, capecitabine, and cetuximab alone and concurrently with external beam radiotherapy for patients with adenocarcinoma of the rectum, stages II and III with wild-type K-ras. - To estimate the 3-year disease-free survival probability in this patient population when treated with this regimen. - To assess the frequency and severity of toxicities associated with this regimen in these patients. - To explore, preliminarily, the association between expression levels of genes involved in the DNA repair, EGFR (epidermal growth factor receptor), angiogenesis, and 5-FU pathway (i.e., k-ras, TS [Thymidylate Synthase], ERCC-1 [excision repair cross complementing-1), TP [Thymidine phosphorylase], DPD [Dihydropyrimidine dehydrogenase], EGFR, VEGF [vascular endothelial growth factor], and IL-8 [interleukin-8]) and pathologic complete response. - To explore, preliminarily, the intratumoral gene expression levels of these genes after completion of study treatment. - To obtain, preliminarily, data on genomic polymorphisms of these genes for correlation with clinical outcome and toxicity. OUTLINE: This is a multicenter study. - Neoadjuvant therapy (course 1): Patients receive oxaliplatin IV over 2 hours once a week for 5 weeks, oral capecitabine twice daily 5 days a week for 5 weeks, and cetuximab IV over 1-2 hours once a week for 5 weeks. - Neoadjuvant therapy with concurrent radiotherapy (course 2): Beginning two weeks later, patients receive oxaliplatin IV over 2 hours once a week in weeks 1, 2, 4, and 5. Patients also receive capecitabine and cetuximab as in course 1. Patients also undergo external beam radiotherapy 5 days a week for 5 weeks beginning in week 1. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo surgery 3-8 weeks after completion of chemoradiotherapy. Blood samples are collected for germline polymorphism testing and tissue samples are collected and assessed for gene expression analysis. After completion of study treatment, patients are followed every 6 months for 4 years.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Southwest Oncology Group.