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

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ClinicalTrials.gov Identifier: NCT00686166
Recruitment Status : Completed
First Posted : May 29, 2008
Results First Posted : February 24, 2016
Last Update Posted : May 18, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Tracking Information
First Submitted Date  ICMJE May 28, 2008
First Posted Date  ICMJE May 29, 2008
Results First Submitted Date  ICMJE January 26, 2016
Results First Posted Date  ICMJE February 24, 2016
Last Update Posted Date May 18, 2018
Study Start Date  ICMJE February 2009
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 26, 2016)
Pathologic Complete Response Rate [ Time Frame: 15-20 weeks from registration ]
Pathologic response is evaluated after the patient has had surgery, and is based on local pathology review of the resected surgical specimen, according to the following: a) Pathologic complete response (pCR): on review of the resected rectal specimen and accompanying lymph nodes, no cancer is recognized by the pathologist; b) Microscopic cancer: gross tumor is not seen by the pathologist but tumor remains in the microscopic analysis of any part of the entire specimen; c) no response: gross cancer is found on pathologic examination of the resected rectal cancer and draining lymph nodes.
Original Primary Outcome Measures  ICMJE
 (submitted: May 28, 2008)
  • Pathologic Complete Response Rate
  • Disease-free survival at 3 years
  • Frequency and severity of toxicities
  • Association between expression levels of genes involved in the DNA repair, EGFR, angiogenesis, and 5-FU pathway with pathologic complete response
  • Intratumoral gene expression levels after completion of study treatment
  • Data on genomic polymorphisms of these genes for correlation with clinical outcome and toxicity
Change History Complete list of historical versions of study NCT00686166 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2016)
  • 3-year Disease-free Survival [ Time Frame: 3 years ]
    From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
  • Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to This Regimen. [ Time Frame: Up to 4 years ]
    Only adverse events that are possibly, probably or definitely related to study regimen are reported.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE S0713: Oxaliplatin, Capecitabine, Cetuximab, and RT Followed By Surgery in Pts W/Stage II or III Rectal Cancer
Official Title  ICMJE A Phase II Study of Oxaliplatin, Capecitabine, Cetuximab and Radiation in Pre-Operative Therapy of Rectal Cancer
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 26, 2016)
83
Original Enrollment  ICMJE
 (submitted: May 28, 2008)
80
Actual Study Completion Date  ICMJE March 2018
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Mexico
 
Administrative Information
NCT Number  ICMJE NCT00686166
Other Study ID Numbers  ICMJE S0713
S0713 ( Other Identifier: SWOG )
U10CA032102 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Southwest Oncology Group
Study Sponsor  ICMJE Southwest Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Cynthia G. Leichman, MD Breastlink
PRS Account Southwest Oncology Group
Verification Date April 2018

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