S0713: Oxaliplatin, Capecitabine, Cetuximab, and RT Followed By Surgery in Pts W/Stage II or III Rectal Cancer
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.
Procedure: therapeutic surgical procedure
Radiation: radiation therapy
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Oxaliplatin, Capecitabine, Cetuximab and Radiation in Pre-Operative Therapy of Rectal Cancer|
- Pathologic Complete Response Rate [ Time Frame: 15-20 weeks from registration ] [ Designated as safety issue: No ]Pathologic response is evaluated after the patient has had surgery, and is based on local pathology review of the resected surgical specimen, according to the following: a) Pathologic complete response (pCR): on review of the resected rectal specimen and accompanying lymph nodes, no cancer is recognized by the pathologist; b) Microscopic cancer: gross tumor is not seen by the pathologist but tumor remains in the microscopic analysis of any part of the entire specimen; c) no response: gross cancer is found on pathologic examination of the resected rectal cancer and draining lymph nodes.
- 3-year Disease-free Survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
- Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to This Regimen. [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]Only adverse events that are possibly, probably or definitely related to study regimen are reported.
|Study Start Date:||February 2009|
|Estimated Study Completion Date:||July 2017|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Experimental: Chemo + Chemo and radiation + Surgery
Chemotherapy Cycle 1 (1 cycle is 35 days):
Chemotherapy+ Radiation Cycle 2:
Therapeutic Surgical procedure: Resection
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
Other Names:Drug: capecitabine
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)
Other Names:Drug: oxaliplatin
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
Other Names:Procedure: therapeutic surgical procedure
Other Name: ResectionRadiation: radiation therapy
IMRT (intensity-modulated radiation therapy)
Other Name: RT
- 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. (Due to advances in methodology, the translational medicine objectives are being reconsidered. Therefore, results for this objective are not reported)
- To explore, preliminarily, the intratumoral gene expression levels of these genes after completion of study treatment.(Due to advances in methodology, the translational medicine objectives are being reconsidered. Therefore, results for this objective are not reported)
- To obtain, preliminarily, data on genomic polymorphisms of these genes for correlation with clinical outcome and toxicity. (Due to advances in methodology, the translational medicine objectives are being reconsidered. Therefore, results for this objective are not reported)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00686166
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|Study Chair:||Cynthia G. Leichman, MD||Breastlink|