Know Cancer

forgot password

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

Phase 2
18 Years
Open (Enrolling)
Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

Thank you

Trial Information

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


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


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


I. To determine the relationship between tumor biomarkers and circulating biomarkers of
vascular response and clinical outcome in metastatic colorectal cancer patients treated with
the sorafenib/bevacizumab combination.

II. As part of ongoing research for NCCTG GI studies, we are banking leftover tissue and
blood products (i.e., plasma, DNA, and buffy coat) for future studies.

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 up periodically for up to 2

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 KRAS testing available

- Prior anti-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

- ECOG performance status 0-1

- Life expectancy ≥ 6 months

- Hemoglobin ≥ 9.0 g/dL

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- WBC ≥ 3,400/mm³

- 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)

- 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

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiaca rrhythmia requiring anti-arrhythmic drugs

- Psychiatric illness or social situations that would limit compliance with study

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Progression-free survival rate

Outcome Description:

The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Outcome Time Frame:

At 3 months

Safety Issue:


Principal Investigator

Axel Grothey

Investigator Role:

Principal Investigator

Investigator Affiliation:

North Central Cancer Treatment Group


United States: Food and Drug Administration

Study ID:




Start Date:

September 2009

Completion Date:

Related Keywords:

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



Mayo Clinic Rochester, Minnesota  55905
Hurley Medical Center Flint, Michigan  48503
Boulder Community Hospital Boulder, Colorado  80301-9019
Porter Adventist Hospital Denver, Colorado  80210
Rose Medical Center Denver, Colorado  80220
Swedish Medical Center Englewood, Colorado  80110
Sky Ridge Medical Center Lone Tree, Colorado  80124
North Suburban Medical Center Thornton, Colorado  80229
Fairview Ridges Hospital Burnsville, Minnesota  55337
Hutchinson Area Health Care Hutchinson, Minnesota  55350
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Geisinger Medical Center Danville, Pennsylvania  17822-0001
Methodist Medical Center of Illinois Peoria, Illinois  61636
Memorial Hospital of South Bend South Bend, Indiana  46601
Virginia Piper Cancer Institute Minneapolis, Minnesota  55407
Via Christi Regional Medical Center Wichita, Kansas  67214
Iowa Methodist Medical Center Des Moines, Iowa  50309
Iowa Lutheran Hospital Des Moines, Iowa  50316-2301
Great Falls Clinic Great Falls, Montana  59405
North Colorado Medical Center Greeley, Colorado  80631
McKee Medical Center Loveland, Colorado  80539
Cancer Center of Kansas - Chanute Chanute, Kansas  66720
Cancer Center of Kansas - Dodge City Dodge City, Kansas  67801
Cancer Center of Kansas - Newton Newton, Kansas  67114
Cancer Center of Kansas - Salina Salina, Kansas  67042
Cancer Center of Kansas - Wellington Wellington, Kansas  67152
Associates in Womens Health Wichita, Kansas  67203
Cancer Center of Kansas - Winfield Winfield, Kansas  67156
Northern Rockies Radiation Oncology Center Billings, Montana  59101
Kalispell Medical Oncology Kalispell, Montana  59901
Kalispell Regional Medical Center Kalispell, Montana  59901
Welch Cancer Center Sheridan, Wyoming  82801
Elkhart General Hospital Elkhart, Indiana  46515
South Bend Clinic South Bend, Indiana  46617
Memorial Hospital Carthage, Illinois  62321
Galesburg Cottage Hospital Galesburg, Illinois  61401
Galesburg Clinic Galesburg, Illinois  61401
Mason District Hospital Havana, Illinois  62644
McDonough District Hospital Macomb, Illinois  61455
BroMenn Regional Medical Center Normal, Illinois  61761
Proctor Hospital Peoria, Illinois  61614
Perry Memorial Hospital Princeton, Illinois  61356
Community Cancer Center of Monroe Monroe, Michigan  48162
Bismarck Cancer Center Bismarck, North Dakota  58501
Grandview Hospital Dayton, Ohio  45405
Lima Memorial Hospital Lima, Ohio  45804
Mercy Hospital of Tiffin Tiffin, Ohio  44883
Fulton County Health Center Wauseon, Ohio  43567
Exempla Lutheran Medical Center Wheat Ridge, Colorado  80033
Eureka Hospital Eureka, Illinois  61530
Mercy Hospital Coon Rapids, Minnesota  55433
Graham Hospital Association Canton, Illinois  61520
Holy Family Medical Center Des Plaines, Illinois  60016
Saint Joseph Medical Center Joliet, Illinois  60435
Pekin Hospital Pekin, Illinois  61554
Medical Oncology and Hematology Associates Des Moines, Iowa  50309
Bixby Medical Center Adrian, Michigan  49221
Saint Joseph Mercy Hospital Ann Arbor, Michigan  48106
Fairview-Southdale Hospital Edina, Minnesota  55435
Abbott-Northwestern Hospital Minneapolis, Minnesota  55407
Regions Hospital Saint Paul, Minnesota  55101
Saint Francis Regional Medical Center Shakopee, Minnesota  55379
Altru Cancer Center Grand Forks, North Dakota  58206
Saint Luke's Hospital Maumee, Ohio  43537
Geisinger Medical Group State College, Pennsylvania  16801
Center for Cancer Care and Research St. Louis, Missouri  63141
Miami Valley Hospital Dayton, Ohio  45409
Hospital District Sixth of Harper County Anthony, Kansas  67003
Cancer Center of Kansas - Fort Scott Fort Scott, Kansas  66701
Cancer Center of Kansas-Independence Independence, Kansas  67301
Lawrence Memorial Hospital Lawrence, Kansas  66044
Bozeman Deaconess Cancer Center Bozeman, Montana  59715
Northern Montana Hospital Havre, Montana  59501
Wayne Hospital Greenville, Ohio  45331
Clinton Memorial Hospital Wilmington, Ohio  45177
Adventist Medical Center Portland, Oregon  97216
Longmont United Hospital Longmont, Colorado  80501
Greene Memorial Hospital Xenia, Ohio  45385
Mayo Clinic in Arizona Scottsdale, Arizona  85259-5404
Mayo Clinic in Florida Jacksonville, Florida  32224
Guardian Oncology and Center for Wellness Missoula, Montana  59804
Hennepin County Medical Center Minneapolis, Minnesota  
Mid Dakota Clinic Bismarck, North Dakota  58501
Presbyterian - Saint Lukes Medical Center - Health One Denver, Colorado  80218
Wichita CCOP Wichita, Kansas  67214-3882
Montana Cancer Consortium CCOP Billings, Montana  59101
Flower Hospital Sylvania, Ohio  43560-2197
Metro-Minnesota CCOP St. Louis Park, Minnesota  
Montana Cancer Specialists Missoula, Montana  59807-7877
Northern Indiana Cancer Research Consortium South Bend, Indiana  
OSF Saint Francis Medical Center Peoria, Illinois  61637
The Medical Center of Aurora Aurora, Colorado  80012
Penrose-Saint Francis Healthcare Colorado Springs, Colorado  80907
Saint Anthony Central Hospital Denver, Colorado  80204
Exempla Saint Joseph Hospital Denver, Colorado  80218
Colorado Cancer Research Program CCOP Denver, Colorado  80224-2522
Saint Mary's Hospital and Regional Medical Center Grand Junction, Colorado  81502
Saint Mary Corwin Medical Center Pueblo, Colorado  81004
Stoffel, Thomas J MD (UIA Investigator) Moline, Illinois  61265
Garneau, Stewart C MD (UIA Investigator) Moline, Illinois  61265
Sharis, Christine M MD (UIA Investigator) Moline, Illinois  61265
Porubcin, Michael MD (UIA Investigator) Moline, Illinois  61265
Community Cancer Center Foundation Normal, Illinois  61761
Illinois CancerCare-Ottawa Clinic Ottawa, Illinois  61350
Ottawa Regional Hospital and Healthcare Center Ottawa, Illinois  61350
Pekin Cancer Treatment Center Pekin, Illinois  61554
Illinois Oncology Research Association CCOP Peoria, Illinois  61615
Illinois CancerCare-Peoria Peoria, Illinois  61615
Illinois Valley Hospital Peru, Illinois  61354
Saint Margaret's Hospital Spring Valley, Illinois  61362
Saint Francis Hospital and Health Centers Beech Grove, Indiana  46107
Reid Hospital and Health Care Services Richmond, Indiana  47374
Constantinou, Costas L MD (UIA Investigator) Bettendorf, Iowa  52722
Cedar Rapids Oncology Association Cedar Rapids, Iowa  52403
Mercy Hospital Cedar Rapids, Iowa  52403
Medical Oncology and Hematology Associates-West Des Moines Clive, Iowa  50325
Iowa Oncology Research Association CCOP Des Moines, Iowa  50309
Mercy Capitol Des Moines, Iowa  50307
Mercy Medical Center - Des Moines Des Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des Moines Des Moines, Iowa  50309
Mercy Medical Center - North Iowa Mason City, Iowa  50401
Mercy Medical Center-Sioux City Sioux City, Iowa  51104
Saint Luke's Regional Medical Center Sioux City, Iowa  51104
Cancer Center of Kansas - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas-Kingman Kingman, Kansas  67068
Cancer Center of Kansas - Parsons Parsons, Kansas  67357
Cancer Center of Kansas - Pratt Pratt, Kansas  67124
Cancer Center of Kansas-Wichita Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas - Main Office Wichita, Kansas  67214
Hickman Cancer Center Adrian, Michigan  49221
Michigan Cancer Research Consortium Community Clinical Oncology Program Ann Arbor, Michigan  48106
Oakwood Hospital Dearborn, Michigan  48123
Saint John Hospital and Medical Center Detroit, Michigan  48236
Green Bay Oncology - Escanaba Escanaba, Michigan  49431
Green Bay Oncology - Iron Mountain Iron Mountain, Michigan  49801
Allegiance Health Jackson, Michigan  49201
Sparrow Hospital Lansing, Michigan  48912
Saint Mary Mercy Hospital Livonia, Michigan  48154
Mercy Memorial Hospital Monroe, Michigan  48162
Saint Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Saint Joseph Mercy Port Huron Port Huron, Michigan  48060
Saint Mary's of Michigan Saginaw, Michigan  48601
Lakeland Hospital St. Joseph, Michigan  49085
Saint John Macomb-Oakland Hospital Warren, Michigan  48093
Miller-Dwan Hospital Duluth, Minnesota  55805
Unity Hospital Fridley, Minnesota  55432
Immanuel-Saint Joseph Hospital-Mayo Health System Mankato, Minnesota  56002
Saint John's Hospital - Healtheast Maplewood, Minnesota  55109
Minnesota Oncology Hematology PA-Maplewood Maplewood, Minnesota  55109
North Memorial Medical Health Center Robbinsdale, Minnesota  55422
Park Nicollet Clinic - Saint Louis Park Saint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-Woodbury Woodbury, Minnesota  55125
Missouri Baptist Medical Center Saint Louis, Missouri  63131
Saint John's Hospital Springfield, Missouri  65804
Hematology-Oncology Centers of the Northern Rockies PC Billings, Montana  59101
Saint Vincent Healthcare Billings, Montana  59101
Billings Clinic Billings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment Center Butte, Montana  59701
Berdeaux, Donald MD (UIA Investigator) Great Falls, Montana  59405
Saint Peter's Community Hospital Helena, Montana  59601
Glacier Oncology PLLC Kalispell, Montana  59901
Community Medical Hospital Missoula, Montana  59801
Saint Patrick Hospital - Community Hospital Missoula, Montana  59802
Saint Alexius Medical Center Bismarck, North Dakota  58501
Good Samaritan Hospital - Dayton Dayton, Ohio  45406
Dayton CCOP Dayton, Ohio  45429
Samaritan North Health Center Dayton, Ohio  45415
Hematology Oncology Center Incorporated Elyria, Ohio  44035
Blanchard Valley Hospital Findlay, Ohio  45840
Atrium Medical Center-Middletown Regional Hospital Franklin, Ohio  45005-1066
Kettering Medical Center Kettering, Ohio  45429
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center Maumee, Ohio  43537
Saint Charles Hospital Oregon, Ohio  43616
North Coast Cancer Care Sandusky, Ohio  44870
Toledo Community Hospital Oncology Program CCOP Toledo, Ohio  43617
Mercy Cancer Center at Saint Anne Mercy Hospital Toledo, Ohio  43623
University of Toledo Toledo, Ohio  43614
Saint Vincent Mercy Medical Center Toledo, Ohio  43608
Upper Valley Medical Center Troy, Ohio  45373
Geisinger Wyoming Valley Wilkes-Barre, Pennsylvania  18711
Fredericksburg Oncology Inc Fredericksburg, Virginia  22401
Mayo Clinic Health System Eau Claire Hospital - Luther Campus Eau Claire, Wisconsin  54703
Midelfort Clinic-Clairemont Campus Eau Claire, Wisconsin  54702
Saint Vincent Hospital Green Bay, Wisconsin  54301
Green Bay Oncology Limited at Saint Mary's Hospital Green Bay, Wisconsin  54303
Saint Mary's Hospital Green Bay, Wisconsin  54303
Green Bay Oncology at Saint Vincent Hospital Green Bay, Wisconsin  54301-3526
Bay Area Medical Center Marinette, Wisconsin  54143
Green Bay Oncology - Oconto Falls Oconto Falls, Wisconsin  54154
Green Bay Oncology - Sturgeon Bay Sturgeon Bay, Wisconsin  54235
North Coast Cancer Care-Clyde Clyde, Ohio  43410
Holy Family Memorial Hospital Manitowoc, Wisconsin  54221
Siouxland Hematology Oncology Associates Sioux City, Iowa  51101
Oncology Associates at Mercy Medical Center Cedar Rapids, Iowa  52403
Sanford Clinic North-Fargo Fargo, North Dakota  58102
Sanford Medical Center-Fargo Fargo, North Dakota  58122
The Toledo Hospital/Toledo Children's Hospital Toledo, Ohio  43606
Genesys Regional Medical Center-West Flint Campus Flint, Michigan  48532
Sanford Clinic North-Bemidgi Bemidji, Minnesota  56601
Essentia Health Duluth Clinic CCOP Duluth, Minnesota  55805
Essentia Health Saint Mary's Medical Center Duluth, Minnesota  55805
Sanford Bismarck Medical Center Bismarck, North Dakota  58501
Toledo Clinic Cancer Centers-Oregon Oregon, Ohio  43616
Geisinger Medical Center-Cancer Center Hazelton Hazleton, Pennsylvania  18201
Community Howard Regional Health Kokomo, Indiana  46904
Indiana University Health La Porte Hospital La Porte, Indiana  46350
Saint Joseph Regional Medical Center-Mishawaka Mishawaka, Indiana  46545-1470
Toledo Clinic Cancer Centers-Bowling Green Bowling Green, Ohio  43402
Toledo Clinic Cancer Centers-Maumee Maumee, Ohio  43537-1839
Toledo Clinic Cancer Centers-Toledo Toledo, Ohio  43623