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 16, 2013
Last verified: April 2013

May 28, 2008
April 16, 2013
February 2009
July 2014   (final data collection date for primary outcome measure)
  • 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 ]
  • 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 ]
Complete list of historical versions of study NCT00686166 on ClinicalTrials.gov Archive Site
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S0713: Oxaliplatin, Capecitabine, Cetuximab, and RT Followed By Surgery in Pts W/Stage II or III Rectal Cancer
A Phase II Study of Oxaliplatin, Capecitabine, Cetuximab and Radiation in Pre-Operative Therapy of 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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Colorectal Cancer
  • 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
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

Interventions:
  • Biological: cetuximab
  • Drug: capecitabine
  • Drug: oxaliplatin
  • Procedure: therapeutic surgical procedure
  • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
80
July 2017
July 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00686166
CDR0000596257, S0713, U10CA032102
Yes
Southwest Oncology Group
Southwest Oncology Group
National Cancer Institute (NCI)
Study Chair: Cynthia G. Leichman, MD Breastlink
Southwest Oncology Group
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP