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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00686166
First received: May 28, 2008
Last updated: April 22, 2014
Last verified: April 2014
  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:


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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 130 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Cynthia G. Leichman, MD Breastlink
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00686166     History of Changes
Other Study ID Numbers: S0713, S0713, U10CA032102
Study First Received: May 28, 2008
Last Updated: April 22, 2014
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:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Fluorouracil
Oxaliplatin
Cetuximab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014