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

Colorectal Cancer Clinical Trial

Official title:

A Phase II Study of Oxaliplatin, Capecitabine, Cetuximab and Radiation in Pre-Operative Therapy of Rectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00686166
• Other study ID #: S0713
• Secondary ID: S0713U10CA032102
• Status: Completed
• Phase: Phase 2
• Start date: February 2009
• Est. completion date: March 2018

Study information

• Verified date: April 2018
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: March 2018
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Rectal Neoplasms

Intervention

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

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)
• 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

Procedure:
• therapeutic surgical procedure
Surgical resection

Radiation:
• radiation therapy
IMRT (intensity-modulated radiation therapy)

Locations

Country	Name	City	State
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	American Fork Hospital	American Fork	Utah
United States	Island Hospital Cancer Care Center at Island Hospital	Anacortes	Washington
United States	AnMed Cancer Center	Anderson	South Carolina
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Southwest Regional Cancer Center - Central	Austin	Texas
United States	Texas Oncology, PA - Austin North	Austin	Texas
United States	Texas Oncology, PA at South Austin Cancer Center	Austin	Texas
United States	Texas Oncology, PA at Texas Oncology Cancer Center - Central	Austin	Texas
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	Highline Medical Center Cancer Center	Burien	Washington
United States	Peninsula Medical Center	Burlingame	California
United States	Sandra L. Maxwell Cancer Center	Cedar City	Utah
United States	Texas Oncology, PA - Cedar Park	Cedar Park	Texas
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Roper St. Francis Cancer Center at Roper Hospital	Charleston	South Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Memorial Hospital Cancer Center - Colorado Springs	Colorado Springs	Colorado
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Bon Secours St. Francis Health System	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Hays Medical Center	Hays	Kansas
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital	Houston	Texas
United States	Veterans Affairs Medical Center - Houston	Houston	Texas
United States	Hutchinson Hospital Corporation	Hutchinson	Kansas
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Swedish Medical Center - Issaquah Campus	Issaquah	Washington
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Kansas City Cancer Centers - North	Kansas City	Missouri
United States	Kansas City Cancer Centers - South	Kansas City	Missouri
United States	Kansas City Cancer Centers - West	Kansas City	Kansas
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Truman Medical Center - Hospital Hill	Kansas City	Missouri
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Columbia Basin Hematology	Kennewick	Washington
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	U.T. Medical Center Cancer Institute	Knoxville	Tennessee
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Kansas City Cancer Centers - East	Lee's Summit	Missouri
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	Logan Regional Hospital	Logan	Utah
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Providence Cancer Center at Providence Hospital	Mobile	Alabama
United States	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	Mercy General Health Partners	Muskegon	Michigan
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Sutter Health - Western Division Cancer Research Group	Novato	California
United States	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah
United States	Kansas City Cancer Centers - Southwest	Overland Park	Kansas
United States	Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	California
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Mount Carmel Regional Cancer Center	Pittsburg	Kansas
United States	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Interlakes Oncology/Hematology PC	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Sutter Cancer Center at Roseville Medical Center	Roseville	California
United States	Texas Oncology, PA - Seton Williamson	Round Rock	Texas
United States	Texas Oncology, PA at Texas Cancer Center Round Rock	Round Rock	Texas
United States	Sutter Cancer Center	Sacramento	California
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
United States	LDS Hospital	Salt Lake City	Utah
United States	California Pacific Medical Center - California Campus	San Francisco	California
United States	Texas Oncology, PA - San Marcos	San Marcos	Texas
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	North Puget Oncology at United General Hospital	Sedro-Woolley	Washington
United States	Kansas City Cancer Center - Shawnee Mission	Shawnee Mission	Kansas
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology, PS	Spokane	Washington
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	St. Francis Comprehensive Cancer Center	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Arizona Cancer Center at UMC Orange Grove	Tucson	Arizona
United States	Arizona Cancer Center at University Medical Center North	Tucson	Arizona
United States	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona
United States	Sutter Solano Medical Center	Vallejo	California
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response Rate	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.	15-20 weeks from registration
Secondary	3-year Disease-free Survival	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.	3 years
Secondary	Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to This Regimen.	Only adverse events that are possibly, probably or definitely related to study regimen are reported.	Up to 4 years