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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
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


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

TERTIARY OBJECTIVES:

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
years.


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
following:

- 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
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

Type of Study:

Interventional

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:

No

Principal Investigator

Axel Grothey

Investigator Role:

Principal Investigator

Investigator Affiliation:

North Central Cancer Treatment Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-01177

NCT ID:

NCT00826540

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

Name

Location

Mayo ClinicRochester, Minnesota  55905
Hurley Medical CenterFlint, Michigan  48503
Boulder Community HospitalBoulder, Colorado  80301-9019
Porter Adventist HospitalDenver, Colorado  80210
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
Sky Ridge Medical CenterLone Tree, Colorado  80124
North Suburban Medical CenterThornton, Colorado  80229
Fairview Ridges HospitalBurnsville, Minnesota  55337
Hutchinson Area Health CareHutchinson, Minnesota  55350
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Memorial Hospital of South BendSouth Bend, Indiana  46601
Virginia Piper Cancer InstituteMinneapolis, Minnesota  55407
Via Christi Regional Medical CenterWichita, Kansas  67214
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Great Falls ClinicGreat Falls, Montana  59405
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Cancer Center of Kansas - ChanuteChanute, Kansas  66720
Cancer Center of Kansas - Dodge CityDodge City, Kansas  67801
Cancer Center of Kansas - NewtonNewton, Kansas  67114
Cancer Center of Kansas - SalinaSalina, Kansas  67042
Cancer Center of Kansas - WellingtonWellington, Kansas  67152
Associates in Womens HealthWichita, Kansas  67203
Cancer Center of Kansas - WinfieldWinfield, Kansas  67156
Northern Rockies Radiation Oncology CenterBillings, Montana  59101
Kalispell Medical OncologyKalispell, Montana  59901
Kalispell Regional Medical CenterKalispell, Montana  59901
Welch Cancer CenterSheridan, Wyoming  82801
Elkhart General HospitalElkhart, Indiana  46515
South Bend ClinicSouth Bend, Indiana  46617
Memorial HospitalCarthage, Illinois  62321
Galesburg Cottage HospitalGalesburg, Illinois  61401
Galesburg ClinicGalesburg, Illinois  61401
Mason District HospitalHavana, Illinois  62644
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Proctor HospitalPeoria, Illinois  61614
Perry Memorial HospitalPrinceton, Illinois  61356
Community Cancer Center of MonroeMonroe, Michigan  48162
Bismarck Cancer CenterBismarck, North Dakota  58501
Grandview HospitalDayton, Ohio  45405
Lima Memorial HospitalLima, Ohio  45804
Mercy Hospital of TiffinTiffin, Ohio  44883
Fulton County Health CenterWauseon, Ohio  43567
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Eureka HospitalEureka, Illinois  61530
Mercy HospitalCoon Rapids, Minnesota  55433
Graham Hospital AssociationCanton, Illinois  61520
Holy Family Medical CenterDes Plaines, Illinois  60016
Saint Joseph Medical CenterJoliet, Illinois  60435
Pekin HospitalPekin, Illinois  61554
Medical Oncology and Hematology AssociatesDes Moines, Iowa  50309
Bixby Medical CenterAdrian, Michigan  49221
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Fairview-Southdale HospitalEdina, Minnesota  55435
Abbott-Northwestern HospitalMinneapolis, Minnesota  55407
Regions HospitalSaint Paul, Minnesota  55101
Saint Francis Regional Medical CenterShakopee, Minnesota  55379
Altru Cancer CenterGrand Forks, North Dakota  58206
Saint Luke's HospitalMaumee, Ohio  43537
Geisinger Medical GroupState College, Pennsylvania  16801
Center for Cancer Care and ResearchSt. Louis, Missouri  63141
Miami Valley HospitalDayton, Ohio  45409
Hospital District Sixth of Harper CountyAnthony, Kansas  67003
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Lawrence Memorial HospitalLawrence, Kansas  66044
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
Northern Montana HospitalHavre, Montana  59501
Wayne HospitalGreenville, Ohio  45331
Clinton Memorial HospitalWilmington, Ohio  45177
Adventist Medical CenterPortland, Oregon  97216
Longmont United HospitalLongmont, Colorado  80501
Greene Memorial HospitalXenia, Ohio  45385
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404
Mayo Clinic in FloridaJacksonville, Florida  32224
Guardian Oncology and Center for WellnessMissoula, Montana  59804
Hennepin County Medical CenterMinneapolis, Minnesota  
Mid Dakota ClinicBismarck, North Dakota  58501
Presbyterian - Saint Lukes Medical Center - Health OneDenver, Colorado  80218
Wichita CCOPWichita, Kansas  67214-3882
Montana Cancer Consortium CCOPBillings, Montana  59101
Flower HospitalSylvania, Ohio  43560-2197
Metro-Minnesota CCOPSt. Louis Park, Minnesota  
Montana Cancer SpecialistsMissoula, Montana  59807-7877
Northern Indiana Cancer Research ConsortiumSouth Bend, Indiana  
OSF Saint Francis Medical CenterPeoria, Illinois  61637
The Medical Center of AuroraAurora, Colorado  80012
Penrose-Saint Francis HealthcareColorado Springs, Colorado  80907
Saint Anthony Central HospitalDenver, Colorado  80204
Exempla Saint Joseph HospitalDenver, Colorado  80218
Colorado Cancer Research Program CCOPDenver, Colorado  80224-2522
Saint Mary's Hospital and Regional Medical CenterGrand Junction, Colorado  81502
Saint Mary Corwin Medical CenterPueblo, 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 FoundationNormal, Illinois  61761
Illinois CancerCare-Ottawa ClinicOttawa, Illinois  61350
Ottawa Regional Hospital and Healthcare CenterOttawa, Illinois  61350
Pekin Cancer Treatment CenterPekin, Illinois  61554
Illinois Oncology Research Association CCOPPeoria, Illinois  61615
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Illinois Valley HospitalPeru, Illinois  61354
Saint Margaret's HospitalSpring Valley, Illinois  61362
Saint Francis Hospital and Health CentersBeech Grove, Indiana  46107
Reid Hospital and Health Care ServicesRichmond, Indiana  47374
Constantinou, Costas L MD (UIA Investigator)Bettendorf, Iowa  52722
Cedar Rapids Oncology AssociationCedar Rapids, Iowa  52403
Mercy HospitalCedar Rapids, Iowa  52403
Medical Oncology and Hematology Associates-West Des MoinesClive, Iowa  50325
Iowa Oncology Research Association CCOPDes Moines, Iowa  50309
Mercy CapitolDes Moines, Iowa  50307
Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des MoinesDes Moines, Iowa  50309
Mercy Medical Center - North IowaMason City, Iowa  50401
Mercy Medical Center-Sioux CitySioux City, Iowa  51104
Saint Luke's Regional Medical CenterSioux City, Iowa  51104
Cancer Center of Kansas - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas-KingmanKingman, Kansas  67068
Cancer Center of Kansas - ParsonsParsons, Kansas  67357
Cancer Center of Kansas - PrattPratt, Kansas  67124
Cancer Center of Kansas-Wichita Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas - Main OfficeWichita, Kansas  67214
Hickman Cancer CenterAdrian, Michigan  49221
Michigan Cancer Research Consortium Community Clinical Oncology ProgramAnn Arbor, Michigan  48106
Oakwood HospitalDearborn, Michigan  48123
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Green Bay Oncology - EscanabaEscanaba, Michigan  49431
Green Bay Oncology - Iron MountainIron Mountain, Michigan  49801
Allegiance HealthJackson, Michigan  49201
Sparrow HospitalLansing, Michigan  48912
Saint Mary Mercy HospitalLivonia, Michigan  48154
Mercy Memorial HospitalMonroe, Michigan  48162
Saint Joseph Mercy OaklandPontiac, Michigan  48341-2985
Saint Joseph Mercy Port HuronPort Huron, Michigan  48060
Saint Mary's of MichiganSaginaw, Michigan  48601
Lakeland HospitalSt. Joseph, Michigan  49085
Saint John Macomb-Oakland HospitalWarren, Michigan  48093
Miller-Dwan HospitalDuluth, Minnesota  55805
Unity HospitalFridley, Minnesota  55432
Immanuel-Saint Joseph Hospital-Mayo Health SystemMankato, Minnesota  56002
Saint John's Hospital - HealtheastMaplewood, Minnesota  55109
Minnesota Oncology Hematology PA-MaplewoodMaplewood, Minnesota  55109
North Memorial Medical Health CenterRobbinsdale, Minnesota  55422
Park Nicollet Clinic - Saint Louis ParkSaint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-WoodburyWoodbury, Minnesota  55125
Missouri Baptist Medical CenterSaint Louis, Missouri  63131
Saint John's HospitalSpringfield, Missouri  65804
Hematology-Oncology Centers of the Northern Rockies PCBillings, Montana  59101
Saint Vincent HealthcareBillings, Montana  59101
Billings ClinicBillings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment CenterButte, Montana  59701
Berdeaux, Donald MD (UIA Investigator)Great Falls, Montana  59405
Saint Peter's Community HospitalHelena, Montana  59601
Glacier Oncology PLLCKalispell, Montana  59901
Community Medical HospitalMissoula, Montana  59801
Saint Patrick Hospital - Community HospitalMissoula, Montana  59802
Saint Alexius Medical CenterBismarck, North Dakota  58501
Good Samaritan Hospital - DaytonDayton, Ohio  45406
Dayton CCOPDayton, Ohio  45429
Samaritan North Health CenterDayton, Ohio  45415
Hematology Oncology Center IncorporatedElyria, Ohio  44035
Blanchard Valley HospitalFindlay, Ohio  45840
Atrium Medical Center-Middletown Regional HospitalFranklin, Ohio  45005-1066
Kettering Medical CenterKettering, Ohio  45429
Toledo Radiation Oncology at Northwest Ohio Onocolgy CenterMaumee, Ohio  43537
Saint Charles HospitalOregon, Ohio  43616
North Coast Cancer CareSandusky, Ohio  44870
Toledo Community Hospital Oncology Program CCOPToledo, Ohio  43617
Mercy Cancer Center at Saint Anne Mercy HospitalToledo, Ohio  43623
University of ToledoToledo, Ohio  43614
Saint Vincent Mercy Medical CenterToledo, Ohio  43608
Upper Valley Medical CenterTroy, Ohio  45373
Geisinger Wyoming ValleyWilkes-Barre, Pennsylvania  18711
Fredericksburg Oncology IncFredericksburg, Virginia  22401
Mayo Clinic Health System Eau Claire Hospital - Luther CampusEau Claire, Wisconsin  54703
Midelfort Clinic-Clairemont CampusEau Claire, Wisconsin  54702
Saint Vincent HospitalGreen Bay, Wisconsin  54301
Green Bay Oncology Limited at Saint Mary's HospitalGreen Bay, Wisconsin  54303
Saint Mary's HospitalGreen Bay, Wisconsin  54303
Green Bay Oncology at Saint Vincent HospitalGreen Bay, Wisconsin  54301-3526
Bay Area Medical CenterMarinette, Wisconsin  54143
Green Bay Oncology - Oconto FallsOconto Falls, Wisconsin  54154
Green Bay Oncology - Sturgeon BaySturgeon Bay, Wisconsin  54235
North Coast Cancer Care-ClydeClyde, Ohio  43410
Holy Family Memorial HospitalManitowoc, Wisconsin  54221
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
Oncology Associates at Mercy Medical CenterCedar Rapids, Iowa  52403
Sanford Clinic North-FargoFargo, North Dakota  58102
Sanford Medical Center-FargoFargo, North Dakota  58122
The Toledo Hospital/Toledo Children's HospitalToledo, Ohio  43606
Genesys Regional Medical Center-West Flint CampusFlint, Michigan  48532
Sanford Clinic North-BemidgiBemidji, Minnesota  56601
Essentia Health Duluth Clinic CCOPDuluth, Minnesota  55805
Essentia Health Saint Mary's Medical CenterDuluth, Minnesota  55805
Sanford Bismarck Medical CenterBismarck, North Dakota  58501
Toledo Clinic Cancer Centers-OregonOregon, Ohio  43616
Geisinger Medical Center-Cancer Center HazeltonHazleton, Pennsylvania  18201
Community Howard Regional HealthKokomo, Indiana  46904
Indiana University Health La Porte HospitalLa Porte, Indiana  46350
Saint Joseph Regional Medical Center-MishawakaMishawaka, Indiana  46545-1470
Toledo Clinic Cancer Centers-Bowling GreenBowling Green, Ohio  43402
Toledo Clinic Cancer Centers-MaumeeMaumee, Ohio  43537-1839
Toledo Clinic Cancer Centers-ToledoToledo, Ohio  43623