S0713: Oxaliplatin, Capecitabine, Cetuximab, and RT Followed By Surgery in Pts W/Stage II or III Rectal Cancer - Full Text View

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	Biological: cetuximab Drug: capecitabine Drug: oxaliplatin Procedure: therapeutic surgical procedure 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 Study of Oxaliplatin, Capecitabine, Cetuximab and Radiation in Pre-Operative Therapy of Rectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Oxaliplatin Capecitabine Cetuximab

U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:

Pathologic complete response rate [ Time Frame: 15-20 weeks from registration ] [ Designated as safety issue: No ]
Disease-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Frequency and severity of toxicities [ Time Frame: Weekly through Week 12 ] [ 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 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Intratumoral gene expression levels after completion of study treatment [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Data on genomic polymorphisms of these genes for correlation with clinical outcome and toxicity [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	February 2009
Estimated Study Completion Date:	July 2017
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Chemo + Chemo and radiation + Surgery 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	Biological: cetuximab 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: IMG-C225 Erbitux NSC-714692 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: Xeloda NSC-712807 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: Eloxatin NSC-266046 Procedure: therapeutic surgical procedure Surgical resection Other Name: Resection Radiation: radiation therapy IMRT (intensity-modulated radiation therapy) Other Name: RT

Arms

Assigned Interventions

Experimental: Chemo + Chemo and radiation + Surgery

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

Biological: cetuximab

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:

IMG-C225
Erbitux
NSC-714692

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:

Xeloda
NSC-712807

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:

Eloxatin
NSC-266046

Procedure: therapeutic surgical procedure

Surgical resection

Other Name: Resection

Radiation: radiation therapy

IMRT (intensity-modulated radiation therapy)

Other Name: RT

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.
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 (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

Contacts and Locations

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

Show 130 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Cynthia G. Leichman, MD

Breastlink

More Information

Additional Information:

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

No publications provided

Responsible Party:	Southwest Oncology Group
ClinicalTrials.gov Identifier:	NCT00686166 History of Changes
Other Study ID Numbers:	CDR0000596257, S0713, U10CA032102
Study First Received:	May 28, 2008
Last Updated:	April 16, 2013
Health Authority:	United States: Federal Government

Keywords provided by Southwest Oncology Group:

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

Additional relevant MeSH terms:

Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Oxaliplatin

Capecitabine
Cetuximab
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 16, 2013