AzTrials
AzTrials

HER2 Positive Breast CarcinomaPhase 2NCT00684983

Capecitabine and Lapatinib Ditosylate With or Without Cixutumumab in Treating Patients With Previously Treated HER2-Positive Stage IIIB-IV Breast Cancer

A Phase 2 study testing Capecitabine, Cixutumumab and Lapatinib Ditosylate in people with HER2 Positive Breast Carcinoma and Recurrent Breast Carcinoma, run by National Cancer Institute (NCI) at 390 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This phase II trial studies capecitabine and lapatinib ditosylate to see how well they work compared with capecitabine, lapatinib ditosylate, and cixutumumab in treating patients with previously treated HER2-positive stage IIIB-IV breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Capecitabine, Cixutumumab and Lapatinib Ditosylate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
390 sitesUnited States
Study dates
30 Jul 2008to 15 Oct 2019
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed, locally advanced: (a T4 primary tumor and stage IIIB or IIIC disease) or metastatic breast cancer that has progressed after treatment with regimens that included trastuzumab and either an anthracycline or a taxane or both
  • NOTE: Agents need not have been given concurrently, nor in the same regimen
  • NOTE: Prior treatment with trastuzumab is required unless there is a contraindication for trastuzumab treatment
  • Pre-treatment requirements:
  • Prior treatment with trastuzumab in the neo-adjuvant, adjuvant or metastatic setting is required
  • NOTE: Prior treatment with trastuzumab is required unless there is a contraindication for trastuzumab treatment
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  • NOTE: Concomitant use of trastuzumab is not allowed in this study
  • Prior chemotherapy allowed in the neo-adjuvant, adjuvant, or metastatic setting; unlimited prior chemotherapy is allowed
  • Prior hormonal therapy allowed in the neo-adjuvant, adjuvant, or metastatic setting; unlimited prior hormonal therapy is allowed
  • HER2 positive, defined as:
  • Validated immunohistochemistry (IHC) assay score of 3+ (defined as uniform, intense staining of > 30% of invasive tumor cells)
  • -OR- Average HER2 gene copy number of > 6
  • -OR- Gene amplified (HER2:D17Z1 ratio > 2.20)
  • Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Hemoglobin > 9.0 g/dL (obtained =< 7 days prior to registration)
  • White blood cells (WBC) >= 3,000/mL (obtained =< 7 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1500/mL (obtained =< 7 days prior to registration)
  • Platelet count >= 75,000/mL (obtained =< 7 days prior to registration)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 7 days prior to registration)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x ULN or SGOT (AST) and SGPT (ALT) =< 5 x ULN if elevations are due to liver metastases (obtained =< 7 days prior to registration)
  • Serum creatinine =< 1.5 x ULN (obtained =< 7 days prior to registration)
  • Creatinine clearance >= 30 mL/min (calculated according to Cockcroft and Gault) (obtained =< 7 days prior to registration)
  • NOTE: In patients with moderate renal impairment (calculated creatinine clearance 30-50 mL/min) at baseline, a dose reduction of the capecitabine starting dose is required
  • Fasting glucose < 120 mg/dL (obtained =< 7 days prior to registration)
  • NOTE: Patients with diabetes are allowed to participate, provided that their blood glucose is within the guidelines above upon enrollment
  • International normalization ratio (INR) =< 1.5 x ULN (obtained =< 7 days prior to registration)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
  • Adequate cardiac function defined as an ejection fraction >= 50% as determined by multi gated acquisition scan (MUGA) or echocardiogram
  • Life expectancy > 3 months
  • Has written informed consent been obtained?
  • Willingness to return to a North Central Cancer Treatment Group (NCCTG) or other participating cooperative group institution for treatment and follow-up
  • Patient willing to provide tissue and blood samples for research purposes
  • Availability of diagnostic material (i.e., diagnostic slides confirming locally advanced/metastatic disease and HER2 stained slides) and operative and pathology reports from diagnosis of locally advanced or metastatic breast cancer
  • NOTE: Biopsy of recurrent disease and submission of these materials is not required if materials available from initial diagnosis of locally advanced/metastatic disease
  • Ability to complete questionnaire(s) by themselves or with assistance

Who cannot join

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception (as determined by the treating physician)
  • Stage III or IV invasive cancer, other than breast cancer, in =< 5 years prior to registration
  • Actively being treated for other malignancy, excepting non-melanotic skin cancer or carcinoma-in-situ of the cervix; if there is a history of prior malignancy, patient must not be receiving other specific treatment for their cancer
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  • New York Heart Association class III or IV cardiovascular disease
  • Current, active hepatic or biliary disease except Gilbert's syndrome or asymptomatic gallstones
  • Evidence of active brain metastasis including leptomeningeal involvement; central nervous system (CNS) metastasis controlled by prior surgery and/or radiotherapy is allowed
  • NOTE: To be considered controlled, there must be at least 2 months of no symptoms or evidence of progression prior to study entry and corticosteroid therapy must have been discontinued
  • Major surgery, chemotherapy, or immunologic therapy =< 4 weeks prior to registration
  • Radiotherapy =< 4 weeks prior to registration, except if to a non-target lesion only; prior radiation to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed; if patient receives single dose radiation for palliation or radiation to non-target lesion, they may immediately proceed to registration without waiting; acute adverse events from radiation must have resolved to =< Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0 grade 1
  • Prior treatment with any therapy targeting IGF-I, IGF-II or its receptors (either monoclonal antibody or tyrosine kinase inhibitor), including but not limited to any of the following (which would have been received on a previous clinical trial):
  • IMC-A12 (cixutumumab)
  • CP-751,871 (figitumumab)
  • AMG-479
  • INSM-18
  • MK0646 (h7C10)
  • SCH717454 (19D12, robatumumab)
  • R1507
  • OSI-906
  • BMS-754807
  • PPP
  • NVP-AEW541
  • AVE-1642
  • MEDI-573
  • Prior therapy with any therapy targeting HER1 (EGFR) and/or HER2 (either monoclonal antibody or tyrosine kinase) other than trastuzumab, including but not limited to any of the following:
  • Lapatinib (Tykerb)
  • Gefitinib (Iressa)
  • Erlotinib (Tarceva)
  • Cetuximab (Erbitux)
  • Panitumumab (Vectibix)
  • Currently receiving treatment with any agents that are contraindicated by study therapies:
  • IMC-A12 - none identified to date
  • Lapatinib - CYP3A4 inhibitors and inducers, including grapefruit and grapefruit juice
  • Capecitabine - warfarin (Coumadin), cimetidine (Tagamet), allopurinol (Lopurin), sorivudine (Usevir) or brivudine (Brivex), ketoconazole (Nizoral), itraconazole (Sporanox), ritonavir (Norvir), amprenavir (Agenerase) or indinavir (Crixivan)
  • Uncontrolled intercurrent illness including, but not limited to:
  • Poorly controlled diabetes
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of the safety of the prescribed regimens
  • Currently receiving treatment in a different clinical study in which investigational procedures are performed or investigational therapies are administered
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive with an acquired immune deficiency syndrome (AIDS)-defining illness; HIV positive patients with cluster of differentiation (CD) 4 count within institutional normal range and no history of an AIDS-defining illness are eligible; however, some antiviral/antiretroviral medications which have CYP3A4 interactions are prohibited on this study

Trial locations and contacts

390 sites in 1 country.

300 sites in 1 country

United States300 sites

  • Avera Cancer Institute-Aberdeen

    Aberdeen, South Dakota, 57401

  • Abington Memorial Hospital

    Abington, Pennsylvania, 19001

  • Bixby Medical Center

    Adrian, Michigan, 49221

  • Hickman Cancer Center

    Adrian, Michigan, 49221

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87102

  • Medini, Eitan MD (UIA Investigator)

    Alexandria, Minnesota, 56308

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • Saint Anthony's Health

    Alton, Illinois, 62002

  • The Don and Sybil Harrington Cancer Center

    Amarillo, Texas, 79106

  • McFarland Clinic PC - Ames

    Ames, Iowa, 50010

  • Cancer Care Center at Island Hospital

    Anacortes, Washington, 98221

  • Michigan Cancer Research Consortium NCORP

    Ann Arbor, Michigan, 48106

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • The Medical Center of Aurora

    Aurora, Colorado, 80012

  • Rush - Copley Medical Center

    Aurora, Illinois, 60504

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Franciscan Saint Francis Health-Beech Grove

    Beech Grove, Indiana, 46107

  • Mary Rutan Hospital

    Bellefontaine, Ohio, 43311

  • Overlake Hospital Medical Center

    Bellevue, Washington, 98004

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Suburban Hospital

    Bethesda, Maryland, 20814

  • University of Iowa Healthcare Cancer Services Quad Cities

    Bettendorf, Iowa, 52722

  • Spectrum Health Big Rapids Hospital

    Big Rapids, Michigan, 49307

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Northern Rockies Radiation Oncology Center

    Billings, Montana, 59101

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • Montana Cancer Consortium NCORP

    Billings, Montana, 59102

  • Saint Vincent Frontier Cancer Center

    Billings, Montana, 59102

  • Mid Dakota Clinic

    Bismarck, North Dakota, 58501

  • Saint Alexius Medical Center

    Bismarck, North Dakota, 58501

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Lynn Regional Cancer Center - West

    Boca Raton, Florida, 33428

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Boulder Community Hospital

    Boulder, Colorado, 80301

  • Toledo Clinic Cancer Centers-Bowling Green

    Bowling Green, Ohio, 43402

  • Bozeman Deaconess Hospital

    Bozeman, Montana, 59715

  • Cox Cancer Center Branson

    Branson, Missouri, 65616

  • Harrison HealthPartners Hematology and Oncology-Bremerton

    Bremerton, Washington, 98310

  • Highline Medical Center-Main Campus

    Burien, Washington, 98166

  • Mills-Peninsula Medical Center

    Burlingame, California, 94010

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Butler Memorial Hospital

    Butler, Pennsylvania, 16001

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Southeast Missouri Hospital

    Cape Girardeau, Missouri, 63701

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Rocky Mountain Oncology

    Casper, Wyoming, 82609

  • East Bay Radiation Oncology Center

    Castro Valley, California, 94546

  • Eden Hospital Medical Center

    Castro Valley, California, 94546

  • Valley Medical Oncology Consultants-Castro Valley

    Castro Valley, California, 94546

  • Mercy Hospital

    Cedar Rapids, Iowa, 52403

  • Oncology Associates at Mercy Medical Center

    Cedar Rapids, Iowa, 52403

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • Cancer Center of Kansas - Chanute

    Chanute, Kansas, 66720

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Medical Oncology and Hematology Associates-West Des Moines

    Clive, Iowa, 50325

  • North Coast Cancer Care-Clyde

    Clyde, Ohio, 43410

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • John B Amos Cancer Center

    Columbus, Georgia, 31904

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Columbus NCI Community Oncology Research Program

    Columbus, Ohio, 43215

  • Grant Medical Center

    Columbus, Ohio, 43215

  • Mount Carmel Health Center West

    Columbus, Ohio, 43222

  • Doctors Hospital

    Columbus, Ohio, 43228

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Danville Regional Medical Center

    Danville, Virginia, 24541

  • Genesis Medical Center - East Campus

    Davenport, Iowa, 52803

  • Genesis Cancer Care Institute

    Davenport, Iowa, 52804

  • Grandview Hospital

    Dayton, Ohio, 45405

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Dayton NCI Community Oncology Research Program

    Dayton, Ohio, 45459

  • Beaumont Hospital - Dearborn

    Dearborn, Michigan, 48124

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Kaiser Permanente-Franklin

    Denver, Colorado, 80205

  • Porter Adventist Hospital

    Denver, Colorado, 80210

  • Presbyterian - Saint Lukes Medical Center - Health One

    Denver, Colorado, 80218

  • SCL Health Saint Joseph Hospital

    Denver, Colorado, 80218

  • Rose Medical Center

    Denver, Colorado, 80220

  • Western States Cancer Research NCORP

    Denver, Colorado, 80222

  • Mercy Capitol

    Des Moines, Iowa, 50307

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Iowa-Wide Oncology Research Coalition NCORP

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Des Moines

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Laurel

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Ascension Saint John Hospital

    Detroit, Michigan, 48236

  • Cancer Center of Kansas - Dodge City

    Dodge City, Kansas, 67801

  • Finley Hospital

    Dubuque, Iowa, 52001

  • Hematology Oncology Associates of Central New York-East Syracuse

    East Syracuse, New York, 13057

  • Fairview-Southdale Hospital

    Edina, Minnesota, 55435

  • Cancer Center of Kansas - El Dorado

    El Dorado, Kansas, 67042

  • Elkhart Clinic

    Elkhart, Indiana, 46514-2098

  • Michiana Hematology Oncology PC-Elkhart

    Elkhart, Indiana, 46514

  • Elkhart General Hospital

    Elkhart, Indiana, 46515

  • Hematology Oncology Center Incorporated

    Elyria, Ohio, 44035

  • Mercy Cancer Center-Elyria

    Elyria, Ohio, 44035

  • Bay Area Breast Surgeons Inc

    Emeryville, California, 94608

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • Green Bay Oncology - Escanaba

    Escanaba, Michigan, 49829

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Saint Francis Hospital

    Federal Way, Washington, 98003

  • Etzell, Paul S MD (UIA Investigator)

    Fergus Falls, Minnesota, 56537

  • Lake Region Healthcare Corporation-Cancer Care

    Fergus Falls, Minnesota, 56537

  • Swenson, Wade II, MD (UIA Investigator)

    Fergus Falls, Minnesota, 56537

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Genesys Regional Medical Center-West Flint Campus

    Flint, Michigan, 48532

  • McLeod Regional Medical Center

    Florence, South Carolina, 29506

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Holy Cross Hospital

    Fort Lauderdale, Florida, 33308

  • Cancer Center of Kansas - Fort Scott

    Fort Scott, Kansas, 66701

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Aurora Cancer Care-Franklin

    Franklin, Wisconsin, 53132

  • Fredericksburg Oncology Inc

    Fredericksburg, Virginia, 22401

  • Valley Medical Oncology Consultants-Fremont

    Fremont, California, 94538

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Glendale Memorial Hospital and Health Center

    Glendale, California, 91204

  • Aurora Cancer Care-Glendale

    Glendale, Wisconsin, 53212

  • Glens Falls Hospital

    Glens Falls, New York, 12801

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • Altru Cancer Center

    Grand Forks, North Dakota, 58201

  • Saint Mary's Hospital and Regional Medical Center

    Grand Junction, Colorado, 81501

  • Cancer Research Consortium of West Michigan NCORP

    Grand Rapids, Michigan, 49503

  • Mercy Health Saint Mary's

    Grand Rapids, Michigan, 49503

  • Spectrum Health at Butterworth Campus

    Grand Rapids, Michigan, 49503

  • Benefis Healthcare- Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Berdeaux, Donald MD (UIA Investigator)

    Great Falls, Montana, 59405

  • Great Falls Clinic

    Great Falls, Montana, 59405

  • North Colorado Medical Center

    Greeley, Colorado, 80631

  • Green Bay Oncology at Saint Vincent Hospital

    Green Bay, Wisconsin, 54301-3526

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Green Bay Oncology Limited at Saint Mary's Hospital

    Green Bay, Wisconsin, 54303

  • Saint Vincent Hospital Cancer Center at Saint Mary's

    Green Bay, Wisconsin, 54303

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • Northern Montana Hospital

    Havre, Montana, 59501

  • Geisinger Medical Center-Cancer Center Hazleton

    Hazleton, Pennsylvania, 18201

  • Saint Peter's Community Hospital

    Helena, Montana, 59601

  • Margaret R Pardee Memorial Hospital

    Hendersonville, North Carolina, 28791

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • Edwards Comprehensive Cancer Center

    Huntington, West Virginia, 25701

  • Hutchinson Area Health Care

    Hutchinson, Minnesota, 55350

  • Cancer Center of Kansas-Independence

    Independence, Kansas, 67301

  • Green Bay Oncology - Iron Mountain

    Iron Mountain, Michigan, 49801

  • Allegiance Health

    Jackson, Michigan, 49201

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Joliet Oncology-Hematology Associates Limited

    Joliet, Illinois, 60435

  • Jupiter Medical Center

    Jupiter, Florida, 33458

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Borgess Medical Center

    Kalamazoo, Michigan, 49048

  • Glacier Oncology PLLC

    Kalispell, Montana, 59901

  • Kalispell Medical Oncology

    Kalispell, Montana, 59901

  • Kalispell Regional Medical Center

    Kalispell, Montana, 59901

  • Kadlec Clinic Hematology and Oncology

    Kennewick, Washington, 99336

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Cancer Center of Kansas-Kingman

    Kingman, Kansas, 67068

  • Wellmont Holston Valley Hospital and Medical Center

    Kingsport, Tennessee, 37660

  • Vidant Oncology-Kinston

    Kinston, North Carolina, 28501

  • Thompson Cancer Survival Center

    Knoxville, Tennessee, 37916

  • University of Tennessee - Knoxville

    Knoxville, Tennessee, 37920

  • Community Howard Regional Health

    Kokomo, Indiana, 46904

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • IU Health La Porte Hospital

    La Porte, Indiana, 46350

  • Kaiser Permanente-Rock Creek

    Lafayette, Colorado, 80026

  • Saint Anthony Hospital

    Lakewood, Colorado, 80228

  • Saint Clare Hospital

    Lakewood, Washington, 98499

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

  • Sparrow Hospital

    Lansing, Michigan, 48912

  • University Medical Center of Southern Nevada

    Las Vegas, Nevada, 89102

  • Nevada Cancer Research Foundation CCOP

    Las Vegas, Nevada, 89106

  • Lawrence Memorial Hospital

    Lawrence, Kansas, 66044

  • Saint Joseph Regional Medical Center

    Lewiston, Idaho, 83501

  • Cancer Center of Kansas-Liberal

    Liberal, Kansas, 67905

  • Saint Rita's Medical Center

    Lima, Ohio, 45801

  • Lima Memorial Hospital

    Lima, Ohio, 45804

  • Meeker County Memorial Hospital

    Litchfield, Minnesota, 55355

  • Saint Mary Mercy Hospital

    Livonia, Michigan, 48154

  • Sky Ridge Medical Center

    Lone Tree, Colorado, 80124

  • Longmont United Hospital

    Longmont, Colorado, 80501

  • McKee Medical Center

    Loveland, Colorado, 80539

  • Holy Family Memorial Hospital

    Manitowoc, Wisconsin, 54221

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Saint John's Hospital - Healtheast

    Maplewood, Minnesota, 55109

  • Marietta Memorial Hospital

    Marietta, Ohio, 45750

  • Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • UP Health System Marquette

    Marquette, Michigan, 49855

  • Contra Costa Regional Medical Center

    Martinez, California, 94553-3156

  • Sovah Health Martinsville

    Martinsville, Virginia, 24115

  • Mercy Medical Center - North Iowa

    Mason City, Iowa, 50401

  • Saint Luke's Hospital

    Maumee, Ohio, 43537

  • Toledo Clinic Cancer Centers-Maumee

    Maumee, Ohio, 43537

  • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center

    Maumee, Ohio, 43537

  • Cancer Center of Kansas - McPherson

    McPherson, Kansas, 67460

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Franciscan Saint Anthony Health-Michigan City

    Michigan City, Indiana, 46360

  • Middlesex Hospital

    Middletown, Connecticut, 06457

  • Orange Regional Medical Center

    Middletown, New York, 10940

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Providence Milwaukie Hospital

    Milwaukie, Oregon, 97222

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Virginia Piper Cancer Institute

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • Trinity Cancer Care Center

    Minot, North Dakota, 58701

  • Michiana Hematology Oncology PC-Mishawaka

    Mishawaka, Indiana, 46545

  • Saint Joseph Regional Medical Center-Mishawaka

    Mishawaka, Indiana, 46545

  • Montana Cancer Specialists

    Missoula, Montana, 59802

  • Saint Patrick Hospital - Community Hospital

    Missoula, Montana, 59802

  • Community Medical Hospital

    Missoula, Montana, 59804

  • Guardian Oncology and Center for Wellness

    Missoula, Montana, 59804

  • Providence Hospital

    Mobile, Alabama, 36608

  • Mercy Memorial Hospital

    Monroe, Michigan, 48162

  • Toledo Clinic Cancer Centers-Monroe

    Monroe, Michigan, 48162

  • McLaren Cancer Institute-Macomb

    Mount Clemens, Michigan, 48043

  • Virtua Memorial

    Mount Holly, New Jersey, 08060

  • Good Samaritan Regional Health Center

    Mount Vernon, Illinois, 62864

  • Knox Community Hospital

    Mount Vernon, Ohio, 43050

  • Skagit Valley Hospital

    Mount Vernon, Washington, 98274

  • El Camino Hospital

    Mountain View, California, 94040

  • Palo Alto Medical Foundation-Camino Division

    Mountain View, California, 94040

  • Mercy Health Partners-Hackley Campus

    Muskegon, Michigan, 49442

  • Mercy Health Mercy Campus

    Muskegon, Michigan, 49444

  • The Hospital of Central Connecticut

    New Britain, Connecticut, 06050

  • Tulane University Health Sciences Center

    New Orleans, Louisiana, 70112

  • Licking Memorial Hospital

    Newark, Ohio, 43055

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • Cancer Center of Kansas - Newton

    Newton, Kansas, 67114

  • Lakeland Hospital Niles

    Niles, Michigan, 49120

  • Southwest VA Regional Cancer Center

    Norton, Virginia, 24273

  • Fisher-Titus Medical Center

    Norwalk, Ohio, 44857

  • Sutter Cancer Research Consortium

    Novato, California, 94945

  • Highland General Hospital

    Oakland, California, 94602

  • Alta Bates Summit Medical Center - Summit Campus

    Oakland, California, 94609

  • Bay Area Tumor Institute

    Oakland, California, 94609

  • Hematology and Oncology Associates-Oakland

    Oakland, California, 94609

  • Tom K Lee Inc

    Oakland, California, 94609

  • Saint Vincent Hospital Cancer Center at Oconto Falls

    Oconto Falls, Wisconsin, 54154

  • Providence - Saint Peter Hospital

    Olympia, Washington, 98506-5166

  • Saint Charles Hospital

    Oregon, Ohio, 43616

  • Toledo Clinic Cancer Centers-Oregon

    Oregon, Ohio, 43616

  • Providence Willamette Falls Medical Center

    Oregon City, Oregon, 97045

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • Ottumwa Regional Health Center

    Ottumwa, Iowa, 52501

  • Desert Regional Medical Center

    Palm Springs, California, 92262

  • Palo Alto Medical Foundation Health Care

    Palo Alto, California, 94301

  • Cancer Center of Kansas - Parsons

    Parsons, Kansas, 67357

  • Singing River Hospital

    Pascagoula, Mississippi, 39581

  • Sacred Heart Hospital

    Pensacola, Florida, 32504

  • Valley Care Health System - Pleasanton

    Pleasanton, California, 94588

  • Valley Medical Oncology Consultants

    Pleasanton, California, 94588

  • Michiana Hematology Oncology PC-Plymouth

    Plymouth, Indiana, 46563

  • Saint Joseph Mercy Oakland

    Pontiac, Michigan, 48341

  • Lake Huron Medical Center

    Port Huron, Michigan, 48060

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Adventist Medical Center

    Portland, Oregon, 97216

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Southern Ohio Medical Center

    Portsmouth, Ohio, 45662

  • Harrison HealthPartners Hematology and Oncology-Poulsbo

    Poulsbo, Washington, 98370

  • Cancer Center of Kansas - Pratt

    Pratt, Kansas, 67124

  • Saint Mary Corwin Medical Center

    Pueblo, Colorado, 81004

  • MultiCare Good Samaritan Hospital

    Puyallup, Washington, 98372

  • Aurora Cancer Care-Racine

    Racine, Wisconsin, 53406

  • Reid Health

    Richmond, Indiana, 47374

  • North Memorial Medical Health Center

    Robbinsdale, Minnesota, 55422

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Cancer Trials Support Unit

    Rockville, Maryland, 20850-2062

  • Delbert Day Cancer Institute at PCRMC

    Rolla, Missouri, 65401

  • Ascension Saint Mary's Hospital

    Saginaw, Michigan, 48601

  • Coborn Cancer Center at Saint Cloud Hospital

    Saint Cloud, Minnesota, 56303

  • Saint Cloud Hospital

    Saint Cloud, Minnesota, 56303

  • Lakeland Medical Center Saint Joseph

    Saint Joseph, Michigan, 49085

  • Marie Yeager Cancer Center

    Saint Joseph, Michigan, 49085

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Cancer Center of Kansas - Salina

    Salina, Kansas, 67401

  • Salinas Valley Memorial

    Salinas, California, 93901

  • California Pacific Medical Center-Pacific Campus

    San Francisco, California, 94115

  • Doctors Medical Center- JC Robinson Regional Cancer Center

    San Pablo, California, 94806

  • North Coast Cancer Care

    Sandusky, Ohio, 44870

Other trials in United States

About this study

Official title: Randomized Phase II Trial of Capecitabine and Lapatinib With or Without IMC-A12 in Patients With HER2 Positive Breast Cancer Previously Treated With Trastuzumab and an Anthracycline and/or a Taxane

This phase II trial studies capecitabine and lapatinib ditosylate to see how well they work compared with capecitabine, lapatinib ditosylate, and cixutumumab in treating patients with previously treated HER2-positive stage IIIB-IV breast cancer. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with cixutumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether capecitabine and lapatinib ditosylate are more effective when given with or without cixutumumab in treating breast cancer that has spread nearby or to other areas of the body.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare progression-free survival of HER2+ breast cancer patients randomized to receive lapatinib ditosylate (lapatinib) and capecitabine +/- cixutumumab (IMC-A12).

SECONDARY OBJECTIVES:

  1. To assess the safety and tolerability of lapatinib and capecitabine +/- IMC-A12 in HER2+ breast cancer patients.

II. To compare the overall survival time, time to treatment failure, confirmed tumor response rate, and duration of response of lapatinib and capecitabine +/- IMC-A12 in HER2+ breast cancer patients.

III. To assess patient compliance per treatment arm and to compare overall quality of life and treatment side effects via patient-reported outcomes between treatment arms.

TRANSLATIONAL RESEARCH OBJECTIVES:

  1. To determine the role of the following in predicting response to lapatinib and capecitabine +/- IMC-A12:

Ia. Expression patterns and/or activation IGF- and ErbB family of receptors and signaling molecules in formalin-fixed, paraffin-embedded breast tumor tissue.

Ib. Expression patterns and/or activation IGF- and ErbB receptors and signaling molecules in circulating tumor cells from breast cancer patients.

Ic. Changes in expression patterns and/or activation IGF- and ErbB receptors and signaling molecules following treatment with lapatinib and capecitabine +/- IMC-A12 in circulating tumor cells from breast cancer patients.

Id. Expression patterns of IGF-1, IGF-II, insulin, growth hormone, and the IGF binding proteins in the serum of breast cancer patients.

Ie. Changes in expression patterns of IGF-1, IGF-II, insulin, growth hormone, and the IGF binding proteins in the serum of breast cancer patients.

II. Banking of paraffin-embedded tissue blocks/slides and blood products (i.e., serum, plasma, and buffy coat) for future studies.

III. To assess the proportion of patients whose pathologic specimens were correctly diagnosed as HER2 positive (according to 2007 American Society of Clinical Oncology [ASCO] College of American Pathologist [CAP] guidelines) metastatic breast cancer.

OUTLINE: The first 10 patients enrolled on this study are assigned to cohort I (safety analysis). All other patients are assigned to cohort II (randomized treatment).

COHORT I (SAFETY ANALYSIS, closed to accrual): Patients receive cixutumumab intravenously (IV) over 1 hour on days 1, 8, and 15. Patients also receive capecitabine orally (PO) twice daily (BID) on days 1-14 and lapatinib ditosylate PO once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

COHORT II (RANDOMIZED TREATMENT): Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive capecitabine PO BID on days 1-14 and lapatinib ditosylate PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive capecitabine and lapatinib ditosylate as in Arm A. Patients also receive cixutumumab IV over 1 hour on days 1, 8, and 15. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months until disease progression and then every 6 months for up to 5 years.

Being tested
Capecitabine, Cixutumumab, Lapatinib Ditosylate, Quality-of-Life Assessment
Keywords
IGF-1R, IMC-A12
Medical subject headings
Breast Neoplasms, Insulin-Like Growth Factor I, Resistance To

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    Given PO

  • CixutumumabBiological

    Also called Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12, IMC-A12

    Given IV

  • Lapatinib DitosylateDrug

    Also called Tykerb

    Given PO

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT00684983
Study groupRoleWhat they receive
Arm A (lapatinib ditosylate, capecitabine)Active comparatorPatients receive capecitabine PO BID on days 1-14 and lapatinib ditosylate PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Capecitabine; Drug: Lapatinib Ditosylate; Other: Quality-of-Life Assessment
Arm B (cixutumumab, lapatinib ditosylate, capecitabine)ExperimentalPatients receive capecitabine and lapatinib ditosylate as in Arm A. Patients also receive cixutumumab IV over 1 hour on days 1, 8, and 15. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Capecitabine; Biological: Cixutumumab; Drug: Lapatinib Ditosylate; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    Analysis of the primary endpoint, PFS, will be performed using Cox regression with treatment group as a single covariate.

    Measured: From randomization to the earliest date of documentation of disease progression, up to 5 years

Secondary outcomes (5)

  1. Overall Survival

    Median Survival time (months)

    Measured: From randomization to death due to any cause, up to 5 years

  2. Time to Treatment Failure

    Distribution estimated by the Kaplan-Meier (1958) method for each treatment arm.

    Measured: From the date of randomization to the date at which the patient is removed from treatment due to progression, adverse events, or refusal, up to 5 years

  3. Confirmed Tumor Response, Defined as Either a Complete Response (CR) or Partial Response (PR) Noted as the Objective Status on 2 Consecutive Evaluations at Least 6 Weeks Apart, Assessed by Response Evaluation Criteria for Solid Tumors (RECIST)

    Measured: Up to 5 years

  4. Duration of Response

    Distribution estimated by the Kaplan-Meier (1958) method for each treatment arm.

    Measured: Up to 5 years

  5. Adverse Event Profile of Capecitabine and Lapatinib With and Without IMC-A12 (Using NCI CTCAE v3.0)

    All eligible patients that have initiated treatment will be considered evaluable for assessing adverse event rate(s) according to CTCAE v3.0 within each treatment arm. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

    4/19 (21.05%) 14/45 (31.11%)

    Measured: Baseline to 30 days past end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 May 2008 (estimated)
  2. Study start30 Jul 2008
  3. Primary completion7 Jan 2014
  4. Study completion15 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00684983
Sponsor's protocol ID
NCI-2009-00665
Other IDs
NCI-2009-00665, PN0733_A15PAMDREVW01, NCCTG N0733, CDR0000596070, NCCTG-N0733, N0733, N0733, U10CA180821
Status last verified
Mar 2020
First submitted
22 May 2008
Last updated
24 Mar 2020
Data monitoring committee
Yes

Publications

  • Haddad TC, He J, O'Sullivan CC, Chen B, Northfelt D, Dueck AC, Ballman KV, Tenner KS, Linden H, Sparano JA, Hopkins JO, De Silva C, Perez EA, Haluska P, Goetz MP. Randomized Phase II Trial of Capecitabine and Lapatinib with or without IMC-A12 (Cituxumumab) in Patients with HER2-Positive Advanced Breast Cancer Previously Treated with Trastuzumab and Chemotherapy: NCCTG N0733 (Alliance). Breast Cancer Res Treat. 2021 Jul;188(2):477-487. doi: 10.1007/s10549-021-06221-8. Epub 2021 Apr 14.

    PubMed 33852121

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