Oxaliplatin, Capecitabine, Cetuximab, and Radiation Therapy Followed By Surgery in Treating Patients With Stage II or Stage III Rectal Cancer - Full Text View

Sponsors and Collaborators:	Southwest Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00686166

Purpose

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.

Condition	Intervention	Phase
Colorectal Cancer	Drug: capecitabine Drug: cetuximab Drug: oxaliplatin Procedure: gene expression analysis Procedure: laboratory biomarker analysis Procedure: neoadjuvant therapy Procedure: polymorphism analysis Procedure: radiation therapy Procedure: therapeutic surgical procedure	Phase II

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Capecitabine Oxaliplatin Cetuximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Study of Oxaliplatin, Capecitabine, Cetuximab and Radiation in Pre-Operative Therapy of Rectal Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pathologic complete response rate [ Designated as safety issue: No ]
Disease-free survival at 3 years [ Designated as safety issue: No ]
Frequency and severity of toxicities [ Designated as safety issue: Yes ]
Association between expression levels of genes involved in the DNA repair, EGFR, angiogenesis, and 5-FU pathway with pathologic complete response [ Designated as safety issue: No ]
Intratumoral gene expression levels after completion of study treatment [ Designated as safety issue: No ]
Data on genomic polymorphisms of these genes for correlation with clinical outcome and toxicity [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	December 2008
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

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 pre-operatively 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, angiogenesis, and 5-FU pathway (i.e., TS, ERCC-1, TP, DPD, GST-P1, XPD, EGFR, VEGF, IL-8, and Cox-2) 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 or SGPT ≤ 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00686166

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Cynthia G. Leichman, MD

Desert Regional Medical Center Comprehensive Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000596257, SWOG-S0713
Study First Received:	May 28, 2008
Last Updated:	October 23, 2008
ClinicalTrials.gov Identifier:	NCT00686166
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the rectum
stage II rectal cancer
stage III rectal cancer

Study placed in the following topic categories:

Capecitabine
Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Cetuximab
Colonic Diseases
Intestinal Diseases
Rectal Diseases

Intestinal Neoplasms
Rectal neoplasm
Oxaliplatin
Digestive System Diseases
Gastrointestinal Neoplasms
Adenocarcinoma
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009