Clinical trial NCT00686166
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the rectum stage IIA rectal cancer stage IIB rectal cancer stage IIC rectal cancer stage IIIA rectal cancer stage IIIB rectal cancer stage IIIC rectal cancer
Sponsor: SWOG Cancer Research Network
Start date: 2009-02-01; Completion date: 2018-03-01
Enrollment: 83 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed 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. (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.

Arms: arm 1: 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
Interventions: intervention 1: cetuximab intervention 2: capecitabine intervention 3: oxaliplatin intervention 4: therapeutic surgical procedure intervention 5: radiation therapy
Intervention descriptions: intervention 1: 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 intervention 2: 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) intervention 3: 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 intervention 4: Surgical resection intervention 5: IMRT (intensity-modulated radiation therapy)

Protocol documents: