Sorafenib and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

Recurrent Rectal Cancer Clinical Trial

Official title:

Phase II Study of Sorafenib/Avastin® as Salvage Therapy in Patients With Metastatic Colorectal Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00826540
• Other study ID #: NCCTG-N054C
• Secondary ID: NCI-2009-01177U1
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 21, 2009
• Last updated: July 1, 2016
• Start date: September 2009

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase II trial is studying how well giving sorafenib together with bevacizumab works in treating patients with metastatic colorectal cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Sorafenib and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with bevacizumab may kill more tumor cells

Description:

PRIMARY OBJECTIVES:

I. Evaluate proportion of patients who are progression-free at 3 months (in historic comparison with results for single-agent bevacizumab in ECOG 3200).

SECONDARY OBJECTIVES:

I. Response rate (RR) II. Overall survival (OS) III. Safety IV. Feasibility

OUTLINE: This is a multicenter study.

Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies.

After completion of study treatment, patients are followed periodically for up to 2 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 83
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of stage IV colorectal cancer (histologic proof is not required)

• Measurable disease

• Spiral CT scan required for both pre- and post-treatment tumor assessments of lesions measuring 1-2 cm

• Progressive disease during or within 6 months of most recent prior chemotherapy regimen (bevacizumab, fluoropyrimidine, oxaliplatin, or irinotecan-based treatment) OR considered ineligible for standard therapy

• Documentation of submission of tumor material for Kirsten Rat Sarcoma (KRAS) testing available

• Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g., cetuximab or panitumumab) required for patients with wild-type KRAS tumor

• No known brain metastasis

• Patients with neurological symptoms must undergo a CT scan or MRI of the brain to exclude brain metastasis

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

• Life expectancy = 6 months

• Hemoglobin = 9.0 g/dL

• Absolute neutrophil count (ANC) = 1,500/mm³

• Platelet count = 100,000/mm³

• White blood cell count (WBC) = 3,400/mm³

• International normalized ratio (INR) < 1.5 (= 3.0 if on anti-coagulation therapy [e.g., warfarin or heparin])

• Total bilirubin = 1.5 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST) = 2.5 times ULN (= 5 times ULN if there is liver involvement)

• Alkaline phosphatase = 3 times ULN

• Creatinine = 1.5 times ULN

• Urine protein:creatinine ratio < 1 OR urine dipstick < 2+ OR urine protein < 1,000 mg by 24-hour urine collection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for = 6 months after completion of study treatment (= 2 weeks after completion of treatment with sorafenib tosylate alone)

• Willing to provide mandatory blood samples for translational research studies

• Able to swallow whole pills

• No inadequately controlled hypertension (i.e., systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg on anti-hypertensive medications)

• No prior hypertensive crisis or hypertensive encephalopathy

• No myocardial infarction or unstable angina within the past 6 months

• No congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

• No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months

• No hemorrhage or bleeding event > grade 3 within the past 4 weeks

• No evidence or history of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)

• No greater than normal risk of bleeding

• No active or recent hemoptysis (= ½ teaspoon of bright red blood per episode) within the past 30 days

• No concurrent uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia requiring anti-arrhythmic drugs

• Psychiatric illness or social situations that would limit compliance with study requirements

• No known HIV infection or chronic hepatitis B or C infection

• No serious, non-healing wound, active ulcer, or untreated bone fracture

• Patients with fractures secondary to metastatic disease are eligible after appropriate radiotherapy

• No significant traumatic injury within the past 4 weeks

• No known or suspected allergy or hypersensitivity to any component of bevacizumab, sorafenib tosylate, or their excipients or to any other agent given in the course of this study

• No malabsorption problem

• None of the following within the past 6 months:

• Significant vascular disease (e.g., aortic aneurysm or aortic dissection)

• Peripheral arterial thrombosis

• Symptomatic peripheral vascular disease

• Abdominal fistula

• Gastrointestinal perforation

• Intra-abdominal abscess

• No other active malignancy within the past 3 years except non melanoma skin cancer or carcinoma in situ of the cervix

• Prior malignancy allowed provided patient is not receiving other specific treatment for that malignancy (other than hormonal therapy)

• No other concurrent investigational agent for this cancer

• Prior radiotherapy allowed

• No prior sorafenib tosylate

• No prior discontinuation of bevacizumab due to adverse events

• More than 4 weeks since prior and no concurrent participation in any other experimental drug study

• More than 4 weeks since prior St. John's wort or rifampin

• More than 4 weeks since prior and no concurrent major surgical procedure or open biopsy

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

• No concurrent anticoagulant, except low-dose warfarin or heparin for deep venous thrombosis prophylaxis

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Rectal Neoplasms
• Recurrent Colon Cancer
• Recurrent Rectal Cancer
• Stage IV Colon Cancer
• Stage IV Rectal Cancer

Intervention

Drug:
• sorafenib tosylate
Given orally

Biological:
• bevacizumab
Given IV

Locations

Country	Name	City	State
United States	Bixby Medical Center	Adrian	Michigan
United States	Hickman Cancer Center	Adrian	Michigan
United States	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Hospital District Sixth of Harper County	Anthony	Kansas
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Saint Francis Hospital and Health Centers	Beech Grove	Indiana
United States	Sanford Clinic North-Bemidgi	Bemidji	Minnesota
United States	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa
United States	Billings Clinic	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies PC	Billings	Montana
United States	Montana Cancer Consortium CCOP	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Saint Alexius Medical Center	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Boulder Community Hospital	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Graham Hospital Association	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Association	Cedar Rapids	Iowa
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	North Coast Cancer Care-Clyde	Clyde	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton CCOP	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Oakwood Hospital	Dearborn	Michigan
United States	Colorado Cancer Research Program CCOP	Denver	Colorado
United States	Exempla Saint Joseph Hospital	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	Saint Anthony Central Hospital	Denver	Colorado
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa Oncology Research Association CCOP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Capitol	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Essentia Health Duluth Clinic CCOP	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Mayo Clinic Health System Eau Claire Hospital - Luther Campus	Eau Claire	Wisconsin
United States	Midelfort Clinic-Clairemont Campus	Eau Claire	Wisconsin
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Hematology Oncology Center Incorporated	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Eureka Hospital	Eureka	Illinois
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Medical Center-Fargo	Fargo	North Dakota
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology Inc	Fredericksburg	Virginia
United States	Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Wayne Hospital	Greenville	Ohio
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	Geisinger Medical Center-Cancer Center Hazelton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Allegiance Health	Jackson	Michigan
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kettering Medical Center	Kettering	Ohio
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Indiana University Health La Porte Hospital	La Porte	Indiana
United States	Sparrow Hospital	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Lima Memorial Hospital	Lima	Ohio
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Immanuel-Saint Joseph Hospital-Mayo Health System	Mankato	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Saint Luke's Hospital	Maumee	Ohio
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Community Medical Hospital	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois
United States	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois
United States	Sharis, Christine M MD (UIA Investigator)	Moline	Illinois
United States	Stoffel, Thomas J MD (UIA Investigator)	Moline	Illinois
United States	Holy Family Medical Center	Monmouth	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital	Monroe	Michigan
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin
United States	Saint Charles Hospital	Oregon	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois Oncology Research Association CCOP	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Adventist Medical Center	Portland	Oregon
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Reid Hospital and Health Care Services	Richmond	Indiana
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic	Rochester	Minnesota
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Center for Cancer Care and Research	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Metro-Minnesota CCOP	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Hematology Oncology Associates	Sioux City	Iowa
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Saint Margaret's Hospital	Spring Valley	Illinois
United States	Saint John's Hospital	Springfield	Missouri
United States	Lakeland Hospital	St. Joseph	Michigan
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Flower Hospital	Sylvania	Ohio
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	Mercy Cancer Center at Saint Anne Mercy Hospital	Toledo	Ohio
United States	Saint Vincent Mercy Medical Center	Toledo	Ohio
United States	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	University of Toledo	Toledo	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Main Office	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita CCOP	Wichita	Kansas
United States	Geisinger Wyoming Valley	Wilkes-Barre	Pennsylvania
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota
United States	Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival Rate	The primary endpoint of this trial is progression free survival at 3 months. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be considered evaluable. Patients lost to follow-up before 3 months (e.g., progression, refusing further treatment, etc.) will be considered treatment failures. All eligible patients will be followed until death or a minimum of 3 years. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients.; Progression is defined as at least a 20% increase in the sum of longest liameter of target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.	At 3 months	No
Secondary	Response Rate	Simple frequency analysis will be conducted to see if response rate is related to prior treatment and the selected tumor biomarkers. Descriptive statistics will be used to investigate how prior treatment affects various other measures as well.	Up to 2 years	No
Secondary	Overall Survival	The distribution of overall survival will be estimated using Kaplan-Meier methodology.	Time from registration to death, assessed up to 2 years	No
Secondary	Feasibility of Study Treatment	Will be evaluated based on the number of patients who are able to; > tolerate the regimen, how long they tolerate it and whether they elect to stop treatment.	Up to 2 years	No