Combination Chemotherapy and Bevacizumab in Treating Patients With Stage IV Colon Cancer That Cannot Be Removed By Surgery

Colorectal Cancer Clinical Trial

Official title:

A Phase II Trial of 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) Chemotherapy Plus Bevacizumab for Patients With Unresectable Stage IV Colon Cancer and a Synchronous Asymptomatic Primary Tumor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00321828
• Other study ID #: NSABP C-10
• Secondary ID: U10CA012027CDR00
• Status: Completed
• Phase: Phase 2
• Start date: March 2006
• Est. completion date: December 2012

Study information

• Verified date: March 2024
• Source: NSABP Foundation Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, 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 bevacizumab, 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. Bevacizumab may also stop the growth of colon cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bevacizumab works in treating patients with stage IV colon cancer that cannot be removed by surgery.

Description:

OBJECTIVES:

Primary

• Determine the rate of major morbidity in patients with unresectable stage IV colon cancer and a synchronous asymptomatic primary tumor treated with fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX6) in combination with bevacizumab without resection of the primary tumor.

Secondary

• Determine the rate of specific events related to the intact primary tumor requiring hospitalization or a major intervention but not requiring surgery.

• Determine the rate of ≥ grade 3 toxicity as defined by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) that is related to study therapy prior to disease progression.

• Determine overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV given concurrently with leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years after study entry.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: December 2012
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the colon

• No histological findings other than adenocarcinoma of the colon

• If the primary colon tumor and the metastatic lesions have been identified at the same time and it is not possible to biopsy the colonic lesion, the patient will be eligible without histologic confirmation of the primary cancer of the colon as long as other radiographic studies or scans document the characteristics of a colon cancer AND the biopsy of a metastatic site confirms diagnosis of adenocarcinoma suggestive of a primary tumor of the colon

• Unresected primary tumor of the colon AND radiographically confirmed metastatic colon cancer (single or multiple sites of metastases) that are not considered surgically resectable for cure by chest imaging and CT scan or MRI of the abdomen within the past 4 weeks and by endoscopy within the past 8 weeks

• Asymptomatic primary tumor

• No obstruction, perforation, or active bleeding requiring transfusion

• Distal extent of the tumor must be = 12 cm from the anal verge on endoscopy

• Not a candidate for curative surgical resection of all metastatic and colon primary tumors

• No evidence of Central Nervous System (CNS) metastases

• No recurrent local or metastatic disease after prior adjuvant therapy

• No diagnosis of rectal carcinoma

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Absolute neutrophil count = 1200/mm³

• Platelet count = 100,000/mm³

• Hemoglobin = 9 g/dL

• Aspartate aminotransferase (AST) = 2.5 times upper limit of normal (ULN) (= 5.0 times ULN if liver metastases are present)

• Alkaline phosphatase = 3.0 times ULN (= 5.0 times ULN if liver metastases are present)

• Bilirubin = 1.5 times ULN (= 2.0 times ULN if liver metastases are present)

• Creatinine < 1.8 mg/dL

• Urine dipstick indicating 0-1+ protein

• If dipstick reading is = 2+, a 24-hour urine collection must demonstrate < 1 g of protein

• Prothrombin Time and International Normalized Ratio (PT/INR) = 1.5 unless the patient is on therapeutic doses of warfarin, in which case the following criteria must be met:

• Patient must have an in-range INR (between 2 and 3) on a stable dose of warfarin

• Patient must not have active bleeding or a pathologic condition that is associated with a high risk of bleeding

• Patients with a history of non-colorectal malignancies must be disease free for = 5 years prior to study entry and be deemed at low risk for recurrence

• Patients with the following cancers are eligible if diagnosed and treated within the past 5 years:

• Carcinoma in situ of the colon

• Melanoma in situ

• Basal cell or squamous cell carcinoma of the skin

• Carcinoma in situ of the cervix

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after the completion of study therapy

• No uncontrolled blood pressure (BP), defined as BP > 150/100 mm Hg

• No nonmalignant systemic disease that would preclude any of the study therapy drugs, compromise the safety of the patient, or inhibit the patient's ability to participate in the study, including any of the following:

• New York Heart Association class III or IV cardiac disease

• Myocardial infarction within the past 6 months

• Unstable angina within the past 6 months

• Symptomatic arrhythmia

• No transient ischemic attack or cerebrovascular accident within the past 6 months

• No symptomatic peripheral vascular ischemia within the past 6 months

• No arterial thrombotic event within the past 6 months

• No gastroduodenal ulcer(s) determined by endoscopy to be active

• No gastrointestinal perforation within the past 12 months

• No serious or nonhealing wound, skin ulcer, or bone fracture

• No significant traumatic injury within the past 28 days

• No significant episodes of acute bleeding requiring blood transfusion within the past 6 months

• No clinically significant (= grade 2) peripheral neuropathy (neurosensory or neuromotor toxicity)

• No pulmonary fibrosis or interstitial pneumonitis by chest x-ray

• No psychiatric or addictive disorders or other conditions that would preclude the patient from meeting study requirements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior systemic chemotherapy, radiation therapy, or surgery for this malignancy

• No prior endoscopic management of this malignancy other than biopsy, including endoscopic stent placement, fulguration, or laser treatment

• More than 30 days since prior investigational drugs

• More than 28 days since prior major surgical procedure or open biopsy

• More than 7 days since prior core biopsy or other minor procedure, excluding placement of a vascular access device

• No concurrent major surgery unrelated to intact primary colon cancer

• No concurrent radiotherapy

• No concurrent filgrastim (G-CSF) or pegfilgrastim as primary prophylaxis for neutropenia

• No concurrent halogenated antiviral agents

• No other concurrent investigational drugs

• No other concurrent antineoplastic agents

Related Conditions & MeSH terms

• Colonic Neoplasms
• Colorectal Cancer

Intervention

Biological:
• bevacizumab
bevacizumab 5 mg/kg IV on day 1 every 14 days until excessive toxicity or disease progression

Drug:
• fluorouracil
5-FU 400 mg/m2 IV bolus over 2-4 minutes then 2400 mg/m2 IV continuous infusion over 46 hours on day 1 every 14 days until excessive toxicity or disease progression
• leucovorin
leucovorin 400 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression
• oxaliplatin
Oxaliplatin 85 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression

Locations

Country	Name	City	State
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	McFarland Clinic, PC	Ames	Iowa
United States	Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Baltimore	Maryland
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia
United States	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Oncology Hematology Care, Incorporated - Blue Ash	Cincinnati	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Danville Regional Medical Center	Danville	Virginia
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	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
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	City of Hope Comprehensive Cancer Center	Duarte	California
United States	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland
United States	Hudner Oncology Center at Saint Anne's Hospital - Fall River	Fall River	Massachusetts
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Kaiser Permanente - Fremont	Fremont	California
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	CCOP - Greenville	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Kaiser Permanente Medical Center - Hayward	Hayward	California
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Howard Community Hospital	Kokomo	Indiana
United States	Scripps Cancer Center - San Diego	La Jolla	California
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Lakeland Regional Cancer Center at Lakeland Regional Medical Center	Lakeland	Florida
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Southwest Medical Center	Liberal	Kansas
United States	Meeker County Memorial Hospital	Litchfield	Minnesota
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	St. Barnabas Medical Center Cancer Center	Livingston	New Jersey
United States	Louisville Oncology at Norton Cancer Institute - Louisville	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Riddle Memorial Hospital Cancer Center	Media	Pennsylvania
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Kaiser Permanente Medical Center - Oakland	Oakland	California
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital	Parkersburg	West Virginia
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Kaiser Permanente Medical Center - Redwood City	Redwood City	California
United States	Kaiser Permanente Medical Center - Richmond	Richmond	California
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Kaiser Permanente Medical Center - Roseville	Roseville	California
United States	Kaiser Permanente Medical Center - Sacramento	Sacramento	California
United States	South Sacramento Kaiser-Permanente Medical Center	Sacramento	California
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Kaiser Permanente Medical Office -Vandever Medical Office	San Diego	California
United States	Kaiser Permanente Medical Center - San Francisco Geary Campus	San Francisco	California
United States	Kaiser Permanente Medical Center - Santa Teresa	San Jose	California
United States	Kaiser Foundation Hospital - San Rafael	San Rafael	California
United States	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California
United States	Kaiser Permanente Medical Center - Santa Rosa	Santa Rosa	California
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Hematology and Oncology Associates of Northeastern Pennsylvania	Scranton	Pennsylvania
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	Kaiser Permanente Medical Center - South San Francisco	South San Francisco	California
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	Mercy Medical Center	Springfield	Ohio
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Kaiser Permanente Medical Facility - Stockton	Stockton	California
United States	Cancer Institute at St. Joseph Medical Center	Towson	Maryland
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Associates in Hematology-Oncology, PC at Crozer Regional Cancer Center	Upland	Pennsylvania
United States	Kaiser Permanente Medical Center - Vallejo	Vallejo	California
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Kaiser Permanente Medical Center - Walnut Creek	Walnut Creek	California
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
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	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	CCOP - Main Line Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
NSABP Foundation Inc	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Morbidity Related to the Intact Primary Tumor	Cumulative incidence was used to compute percent probability of morbidity. Cumulative incidence at time t measures the probability of a participant having an event (i.e., Colonic bleeding, perforation, bowel obstruction, or fistula formation requiring surgery or resulting in patient death) over the given duration, t. It involves computing the probability of an event at any observed time (i.e., the number of new cases during a period divided by the number of subjects at risk) and multiplying these successive probabilities by any early computed probability to get the final estimate.	24 months
Secondary	Local Complications as Assessed by Colonic Obstruction Requiring Hospitalization (But Not Surgery) for Medical Management, Stent Placement, Laser Treatment, or Fulguration		Time from start of study through year 5
Secondary	Local Complications as Assessed by Gastrointestinal Bleeding Requiring Transfusion But Not Requiring Surgery		Time from start of study through year 5
Secondary	Local Complications as Assessed by Fistula Formation (Self-draining Enterocutaneous Fistula and Intra-abdominal Abscess Requiring Percutaneous Drainage) Not Requiring Surgery		Time from start of study through year 5
Secondary	Local Complications as Assessed by Other Events Related to the Intact Primary Tumor Which Require Hospitalization But Not Surgery		Time from start of study through year 5
Secondary	Serious Adverse Events (Grades 3, 4, and 5) as Defined by CTCAE v3.0		Time from start of study through year 5
Secondary	Overall Survival as Measured by Death From Any Cause		Time from start of study through year 5