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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

  Hide Study Locations
Locations
United States, Alabama
Providence Cancer Center at Providence Hospital
Mobile, Alabama, United States, 36608
United States, Arizona
Arizona Cancer Center at UMC Orange Grove
Tucson, Arizona, United States, 85704
Arizona Cancer Center at University Medical Center North
Tucson, Arizona, United States, 85719
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724-5024
United States, California
Alta Bates Summit Comprehensive Cancer Center
Berkeley, California, United States, 94704
Peninsula Medical Center
Burlingame, California, United States, 94010
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
Sutter Health - Western Division Cancer Research Group
Novato, California, United States, 94945
Desert Regional Medical Center Comprehensive Cancer Center
Palm Springs, California, United States, 92262
Sutter Cancer Center at Roseville Medical Center
Roseville, California, United States, 95661
Sutter Cancer Center
Sacramento, California, United States, 95816
California Pacific Medical Center - California Campus
San Francisco, California, United States, 94118
Sutter Pacific Medical Foundation
Santa Rosa, California, United States, 95403
Sutter Solano Medical Center
Vallejo, California, United States, 94589
United States, Colorado
Memorial Hospital Cancer Center - Colorado Springs
Colorado Springs, Colorado, United States, 80909
Poudre Valley Hospital
Fort Collins, Colorado, United States, 80524
Front Range Cancer Specialists
Fort Collins, Colorado, United States, 80528
United States, Illinois
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, United States, 62526
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
Regional Cancer Center at Memorial Medical Center
Springfield, Illinois, United States, 62781-0001
United States, Indiana
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, United States, 46107
Reid Hospital & Health Care Services
Richmond, Indiana, United States, 47374
United States, Kansas
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, United States, 66720
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, United States, 67801
Cancer Center of Kansas - Fort Scott
Fort Scott, Kansas, United States, 66701
Hays Medical Center
Hays, Kansas, United States, 67601
Hutchinson Hospital Corporation
Hutchinson, Kansas, United States, 67502
Cancer Center of Kansas-Independence
Independence, Kansas, United States, 67301
Kansas City Cancer Centers - West
Kansas City, Kansas, United States, 66112
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, United States, 67068
Lawrence Memorial Hospital
Lawrence, Kansas, United States, 66044
Cancer Center of Kansas, PA - Liberal
Liberal, Kansas, United States, 67901
Cancer Center of Kansas, PA - Newton
Newton, Kansas, United States, 67114
Kansas City Cancer Centers - Southwest
Overland Park, Kansas, United States, 66210
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, United States, 67357
Mount Carmel Regional Cancer Center
Pittsburg, Kansas, United States, 66762
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, United States, 67124
Tammy Walker Cancer Center at Salina Regional Health Center
Salina, Kansas, United States, 67401
Cancer Center of Kansas, PA - Salina
Salina, Kansas, United States, 67401
Kansas City Cancer Center - Shawnee Mission
Shawnee Mission, Kansas, United States, 66204
St. Francis Comprehensive Cancer Center
Topeka, Kansas, United States, 66606
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, United States, 67152
Wesley Medical Center
Wichita, Kansas, United States, 67214
Associates in Womens Health, PA - North Review
Wichita, Kansas, United States, 67208
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, United States, 67208
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, United States, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
CCOP - Wichita
Wichita, Kansas, United States, 67214
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, United States, 67156
United States, Maryland
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States, 21215
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
Battle Creek Health System Cancer Care Center
Battle Creek, Michigan, United States, 49017
Mecosta County Medical Center
Big Rapids, Michigan, United States, 49307
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
Butterworth Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
CCOP - Grand Rapids
Grand Rapids, Michigan, United States, 49503
Lacks Cancer Center at Saint Mary's Health Care
Grand Rapids, Michigan, United States, 49503
Mercy General Health Partners
Muskegon, Michigan, United States, 49444
Spectrum Health Reed City Hospital
Reed City, Michigan, United States, 49677
Munson Medical Center
Traverse City, Michigan, United States, 49684
United States, Mississippi
University of Mississippi Cancer Clinic
Jackson, Mississippi, United States, 39216
Regional Cancer Center at Singing River Hospital
Pascagoula, Mississippi, United States, 39581
United States, Missouri
Kansas City Cancer Centers - North
Kansas City, Missouri, United States, 64154
Kansas City Cancer Centers - South
Kansas City, Missouri, United States, 64131
Truman Medical Center - Hospital Hill
Kansas City, Missouri, United States, 64108
Kansas City Cancer Centers - East
Lee's Summit, Missouri, United States, 64064
United States, Nebraska
Good Samaritan Cancer Center at Good Samaritan Hospital
Kearney, Nebraska, United States, 68848-1990
United States, New York
Interlakes Oncology/Hematology PC
Rochester, New York, United States, 14623
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233-3549
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
Iredell Memorial Hospital
Statesville, North Carolina, United States, 28677
United States, Ohio
McDowell Cancer Center at Akron General Medical Center
Akron, Ohio, United States, 44307
CCOP - Dayton
Dayton, Ohio, United States, 45420
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, United States, 45409
Samaritan North Cancer Care Center
Dayton, Ohio, United States, 45415
Grandview Hospital
Dayton, Ohio, United States, 45405
Good Samaritan Hospital
Dayton, Ohio, United States, 45406
Blanchard Valley Medical Associates
Findlay, Ohio, United States, 45840
Middletown Regional Hospital
Franklin, Ohio, United States, 45005-1066
Wayne Hospital
Greenville, Ohio, United States, 45331
Charles F. Kettering Memorial Hospital
Kettering, Ohio, United States, 45429
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, United States, 45373-1300
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, United States, 45385
United States, South Carolina
AnMed Cancer Center
Anderson, South Carolina, United States, 29621
Roper St. Francis Cancer Center at Roper Hospital
Charleston, South Carolina, United States, 29401
Bon Secours St. Francis Health System
Greenville, South Carolina, United States, 29601
CCOP - Upstate Carolina
Spartanburg, South Carolina, United States, 29303
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
U.T. Medical Center Cancer Institute
Knoxville, Tennessee, United States, 37920-6999
United States, Texas
Southwest Regional Cancer Center - Central
Austin, Texas, United States, 78705
Texas Oncology, PA - Austin North
Austin, Texas, United States, 78758
Texas Oncology, PA at South Austin Cancer Center
Austin, Texas, United States, 78745
Texas Oncology, PA at Texas Oncology Cancer Center - Central
Austin, Texas, United States, 78731
Texas Oncology, PA - Cedar Park
Cedar Park, Texas, United States, 78613
Baylor University Medical Center - Houston
Houston, Texas, United States, 77030
Ben Taub General Hospital
Houston, Texas, United States, 77030
St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital
Houston, Texas, United States, 77030
Veterans Affairs Medical Center - Houston
Houston, Texas, United States, 77030
Texas Oncology, PA - Seton Williamson
Round Rock, Texas, United States, 78665
Texas Oncology, PA at Texas Cancer Center Round Rock
Round Rock, Texas, United States, 78681
Texas Oncology, PA - San Marcos
San Marcos, Texas, United States, 78666
United States, Utah
American Fork Hospital
American Fork, Utah, United States, 84003
Sandra L. Maxwell Cancer Center
Cedar City, Utah, United States, 84720
Logan Regional Hospital
Logan, Utah, United States, 84321
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
Murray, Utah, United States, 84157
Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
Ogden, Utah, United States, 84403
Utah Valley Regional Medical Center - Provo
Provo, Utah, United States, 84604
Dixie Regional Medical Center - East Campus
Saint George, Utah, United States, 84770
LDS Hospital
Salt Lake City, Utah, United States, 84143
United States, Washington
Island Hospital Cancer Care Center at Island Hospital
Anacortes, Washington, United States, 98221
St. Joseph Cancer Center
Bellingham, Washington, United States, 98225
Olympic Hematology and Oncology
Bremerton, Washington, United States, 98310
Highline Medical Center Cancer Center
Burien, Washington, United States, 98166
Swedish Medical Center - Issaquah Campus
Issaquah, Washington, United States, 98029
Columbia Basin Hematology
Kennewick, Washington, United States, 99336
Skagit Valley Hospital Cancer Care Center
Mount Vernon, Washington, United States, 98274
Harrison Poulsbo Hematology and Onocology
Poulsbo, Washington, United States, 98370
Group Health Central Hospital
Seattle, Washington, United States, 98112
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States, 98195
Harborview Medical Center
Seattle, Washington, United States, 98104
Polyclinic First Hill
Seattle, Washington, United States, 98122
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Seattle, Washington, United States, 98122-4307
North Puget Oncology at United General Hospital
Sedro-Woolley, Washington, United States, 98284
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
Evergreen Hematology and Oncology, PS
Spokane, Washington, United States, 99218
Wenatchee Valley Medical Center
Wenatchee, Washington, United States, 98801-2028
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
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Capecitabine
Cetuximab
Fluorouracil
Oxaliplatin
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014