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

Primary Purpose

Colorectal Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

bevacizumab

fluorouracil

leucovorin

oxaliplatin

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring adenocarcinoma of the colon, stage IV colon cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
City of Hope Comprehensive Cancer Center
Kaiser Permanente - Fremont
Kaiser Permanente Medical Center - Hayward
Scripps Cancer Center - San Diego
Kaiser Permanente Medical Center - Oakland
Kaiser Permanente Medical Center - Redwood City
Kaiser Permanente Medical Center - Richmond
Kaiser Permanente Medical Center - Roseville
South Sacramento Kaiser-Permanente Medical Center
Kaiser Permanente Medical Center - Sacramento
Kaiser Permanente Medical Office -Vandever Medical Office
Kaiser Permanente Medical Center - San Francisco Geary Campus
Kaiser Permanente Medical Center - Santa Teresa
Kaiser Foundation Hospital - San Rafael
Kaiser Permanente Medical Center - Santa Clara Kiely Campus
Kaiser Permanente Medical Center - Santa Rosa
Kaiser Permanente Medical Center - South San Francisco
Kaiser Permanente Medical Facility - Stockton
Kaiser Permanente Medical Center - Vallejo
Kaiser Permanente Medical Center - Walnut Creek
Tunnell Cancer Center at Beebe Medical Center
CCOP - Christiana Care Health Services
Sibley Memorial Hospital
Lakeland Regional Cancer Center at Lakeland Regional Medical Center
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
John H. Stroger, Jr. Hospital of Cook County
Decatur Memorial Hospital Cancer Care Institute
Advocate Lutheran General Cancer Care Center
Regional Cancer Center at Memorial Medical Center
St. Francis Hospital and Health Centers - Beech Grove Campus
Elkhart General Hospital
Howard Community Hospital
Center for Cancer Therapy at LaPorte Hospital and Health Services
Reid Hospital & Health Care Services
CCOP - Northern Indiana CR Consortium
Memorial Hospital of South Bend
Saint Joseph Regional Medical Center
McFarland Clinic, PC
Holden Comprehensive Cancer Center at University of Iowa
McCreery Cancer Center at Ottumwa Regional
Cancer Center of Kansas, PA - Chanute
Cancer Center of Kansas, PA - Dodge City
Cancer Center of Kansas, PA - El Dorado
Cancer Center of Kansas, PA - Kingman
Lawrence Memorial Hospital
Southwest Medical Center
Cancer Center of Kansas, PA - Newton
Cancer Center of Kansas, PA - Parsons
Cancer Center of Kansas, PA - Pratt
Cancer Center of Kansas, PA - Salina
Cancer Center of Kansas, PA - Wellington
Associates in Womens Health, PA - North Review
Cancer Center of Kansas, PA - Medical Arts Tower
Cancer Center of Kansas, PA - Wichita
CCOP - Wichita
Via Christi Cancer Center at Via Christi Regional Medical Center
Cancer Center of Kansas, PA - Winfield
Louisville Oncology at Norton Cancer Institute - Louisville
Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
Union Hospital Cancer Program at Union Hospital
Cancer Institute at St. Joseph Medical Center
Hudner Oncology Center at Saint Anne's Hospital - Fall River
Josephine Ford Cancer Center at Henry Ford Hospital
Borgess Medical Center
West Michigan Cancer Center
Bronson Methodist Hospital
Lakeland Regional Cancer Care Center - St. Joseph
Fairview Ridges Hospital
Mercy and Unity Cancer Center at Mercy Hospital
Fairview Southdale Hospital
Mercy and Unity Cancer Center at Unity Hospital
Hutchinson Area Health Care
Meeker County Memorial Hospital
HealthEast Cancer Care at St. John's Hospital
Minnesota Oncology Hematology, PA - Maplewood
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Hennepin County Medical Center - Minneapolis
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
CCOP - Metro-Minnesota
Park Nicollet Cancer Center
United Hospital
St. Francis Cancer Center at St. Francis Medical Center
Regions Hospital Cancer Care Center
Ridgeview Medical Center
Minnesota Oncology Hematology, PA - Woodbury
Missouri Baptist Cancer Center
Arch Medical Services, Incorporated at Center for Cancer Care and Research
CCOP - Cancer Research for the Ozarks
St. John's Regional Health Center
Hulston Cancer Center at Cox Medical Center South
CCOP - Montana Cancer Consortium
Hematology-Oncology Centers of the Northern Rockies - Billings
Northern Rockies Radiation Oncology Center
St. Vincent Healthcare Cancer Care Services
St. James Healthcare Cancer Care
Great Falls Clinic - Main Facility
Glacier Oncology, PLLC
Kalispell Medical Oncology at KRMC
Kalispell Regional Medical Center
Community Medical Center
Guardian Oncology and Center for Wellness
Montana Cancer Specialists at Montana Cancer Center
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Methodist Estabrook Cancer Center
St. Barnabas Medical Center Cancer Center
Cancer Institute of New Jersey at Cooper - Voorhees
CCOP - Hematology-Oncology Associates of Central New York
Charles R. Wood Cancer Center at Glens Falls Hospital
Wayne Memorial Hospital, Incorporated
Wake Forest University Comprehensive Cancer Center
McDowell Cancer Center at Akron General Medical Center
Mary Rutan Hospital
Aultman Cancer Center at Aultman Hospital
Adena Regional Medical Center
Oncology Hematology Care, Incorporated - Blue Ash
Riverside Methodist Hospital Cancer Care
CCOP - Columbus
Grant Medical Center Cancer Care
Mount Carmel Health - West Hospital
Doctors Hospital at Ohio Health
Grandview Hospital
Good Samaritan Hospital
David L. Rike Cancer Center at Miami Valley Hospital
Samaritan North Cancer Care Center
Veterans Affairs Medical Center - Dayton
CCOP - Dayton
Grady Memorial Hospital
Blanchard Valley Medical Associates
Middletown Regional Hospital
Wayne Hospital
Charles F. Kettering Memorial Hospital
Fairfield Medical Center
Strecker Cancer Center at Marietta Memorial Hospital
Licking Memorial Cancer Care Program at Licking Memorial Hospital
Mercy Medical Center
Community Hospital of Springfield and Clark County
UVMC Cancer Care Center at Upper Valley Medical Center
Mount Carmel St. Ann's Cancer Center
Clinton Memorial Hospital
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Genesis - Good Samaritan Hospital
Bryn Mawr Hospital
Riddle Memorial Hospital Cancer Center
Cancer Center of Paoli Memorial Hospital
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
Allegheny Cancer Center at Allegheny General Hospital
Hematology and Oncology Associates of Northeastern Pennsylvania
Mount Nittany Medical Center
Associates in Hematology-Oncology, PC at Crozer Regional Cancer Center
CCOP - Main Line Health
Lankenau Cancer Center at Lankenau Hospital
CCOP - Greenville
Avera Cancer Institute
Medical X-Ray Center, PC
Sanford Cancer Center at Sanford USD Medical Center
Joe Arrington Cancer Research and Treatment Center
Fletcher Allen Health Care - University Health Center Campus
Danville Regional Medical Center
West Virginia University Health Sciences Center - Charleston
Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital
Marshfield Clinic - Marshfield Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1: Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab

Arm Description

Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Local Complications as Assessed by Colonic Obstruction Requiring Hospitalization (But Not Surgery) for Medical Management, Stent Placement, Laser Treatment, or Fulguration

Local Complications as Assessed by Gastrointestinal Bleeding Requiring Transfusion But Not Requiring Surgery

Local Complications as Assessed by Fistula Formation (Self-draining Enterocutaneous Fistula and Intra-abdominal Abscess Requiring Percutaneous Drainage) Not Requiring Surgery

Local Complications as Assessed by Other Events Related to the Intact Primary Tumor Which Require Hospitalization But Not Surgery

Serious Adverse Events (Grades 3, 4, and 5) as Defined by CTCAE v3.0

Overall Survival as Measured by Death From Any Cause

Full Information

NCT ID

NCT00321828

First Posted

May 2, 2006

Last Updated

January 16, 2013

Sponsor

NSABP Foundation Inc

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00321828

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Completed

Study Start Date

March 2006 (undefined)

Primary Completion Date

November 2009 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

NSABP Foundation Inc

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

Keywords

adenocarcinoma of the colon, stage IV colon cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

90 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1: Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab

Arm Type

Experimental

Arm Description

Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab

Intervention Type

Biological

Intervention Name(s)

bevacizumab

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Other Intervention Name(s)

5-FU

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

leucovorin

Other Intervention Name(s)

leucovorin calcium

Intervention Description

leucovorin 400 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression

Intervention Type

Drug

Intervention Name(s)

oxaliplatin

Intervention Description

Oxaliplatin 85 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression

Primary Outcome Measure Information:

Title

Major Morbidity Related to the Intact Primary Tumor

Description

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Local Complications as Assessed by Colonic Obstruction Requiring Hospitalization (But Not Surgery) for Medical Management, Stent Placement, Laser Treatment, or Fulguration

Time Frame