AzTrials
AzTrials

Recurrent Breast CarcinomaPhase 2NCT02311933

Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer

A Phase 2 study testing Endoxifen Hydrochloride, Laboratory Biomarker Analysis and Pharmacological Study in people with Recurrent Breast Carcinoma and Stage III Breast Cancer AJCC v7, run by National Cancer Institute (NCI) at 559 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This randomized phase II trial studies how well tamoxifen citrate works compared with z-endoxifen hydrochloride in treating patients with breast cancer that has spread to nearby tissue or lymph nodes or other parts of the body and has estrogen receptors but not human epidermal growth factor receptor 2 (HER2) receptors… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Endoxifen Hydrochloride, Laboratory Biomarker Analysis and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
81 participants
Where
559 sitesUnited States
Study dates
28 May 2015to 2 Feb 2027
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • PRE-REGISTRATION ELIGIBILITY CRITERIA
  • Women who agree to undergo a standard of care core biopsy of recurrent or metastatic breast cancer to confirm the ER+ (>= 10% nuclear staining) and HER2 negative status
  • Patient must have been previously treated with an aromatase inhibitor (either letrozole, anastrozole or exemestane) either in the adjuvant or metastatic setting, and have one of the following types of primary or secondary endocrine resistant disease
  • Primary clinical resistance is defined as one of the following:
  • Recurrence within the first 2 years of adjuvant endocrine therapy while on aromatase inhibitor therapy
  • Progression within first 6 months of initiating first-line endocrine therapy (either aromatase inhibitor or fulvestrant containing regimen) for the treatment of metastatic breast cancer
Show all 72Show fewer
  • Secondary clinical resistance is defined as one of the following:
  • Recurrence after year 2 while receiving adjuvant aromatase inhibitor therapy, or within 12 months of completing adjuvant aromatase inhibitor therapy
  • Progression occurring 6 or more months after initiating the first endocrine therapy for metastatic disease (either fulvestrant or aromatase inhibitor containing regimen)
  • Patients with a history of measurable disease as defined by RECIST criteria or bone only disease are eligible; Note: those patients with non-measurable disease and bone metastases are eligible
  • No history of tumors involving spinal cord or heart
  • No current evidence of visceral crisis or lymphangitic spread
  • No known brain metastases
  • Women must be postmenopausal
  • Postmenopausal status is verified by:
  • Prior bilateral surgical oophorectomy, or
  • Age >= 60 years, or
  • Age < 60 with no menses for > 1 year with follicle-stimulating hormone (FSH) and estradiol levels within post menopausal range, according to institutional standard
  • Prior treatment
  • No more than two prior chemotherapy regimens in the metastatic setting
  • Prior treatment with an aromatase inhibitor (either anastrozole, letrozole or exemestane), either in the adjuvant or metastatic setting is required
  • Unlimited prior endocrine regimens in the metastatic setting, which may have included an everolimus or cyclin dependent kinase (CDK) 4/6 inhibitor (such as palbociclib, abemaciclib or ribociclib) containing regimen
  • Prior tamoxifen treatment is allowed in the adjuvant setting, but patients must not have experienced relapse within 1 year of stopping tamoxifen
  • No prior treatment with tamoxifen in the metastatic setting
  • No prior treatment with endoxifen
  • Patients who have not fully recovered from acute, reversible effects of prior therapy regardless of interval since last treatment are not eligible to participate in this study
  • EXCEPTION: neuropathies-if grade 2 neuropathies have been stable for at least 3 months since completion of prior treatment patient is eligible
  • Not receiving any medications or substances that are strong inhibitors of cytochrome P450 family 2, subfamily D, polypeptide 6 (CYP2D6)
  • Not receiving any other investigational agents
  • No uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Uncontrolled symptomatic cardiac arrhythmia
  • Uncontrolled hypertension (defined as blood pressure > 160/90)
  • None of the following co-morbid conditions:
  • Cataracts of grade 2 or greater as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
  • Retinopathy of grade 2 or greater as per CTCAE version 4.0
  • Note: patients that have cataracts that do not require surgery are eligible
  • Note: serious adverse events will be reported on CTEP-Adverse Event Reporting System (AERS) using CTCAE version (v)5.0
  • Deep vein thrombosis/pulmonary embolism (DVT/PE) within the past 6 months
  • Note: patients that are on anticoagulant therapy for maintenance are eligible as long as the DVT and/or PE occurred > 6 months prior to enrollment, and there is no evidence for active thrombosis (either DVT or PE)
  • No other active second malignancy other than non-melanoma skin cancers within 3 years of pre-registration; a second malignancy is not considered active if all treatment for that malignancy is completed and the patient has been disease-free for at least 3 years prior to pre-registration
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
  • Able to swallow oral formulation of the study agent
  • Hemoglobin >= 9 g/dL
  • Platelet count >= 75,000/mm^3
  • Creatinine =< 1.5 x upper limits of normal (ULN)
  • Total bilirubin =< 1.5 x upper limits of normal (ULN)
  • Aspartate aminotransferase (AST) =< 2.5 x upper limits of normal (ULN); for patients with liver metastasis: =< 5 x upper limits of normal (ULN)
  • REGISTRATION ELIGIBILITY CRITERIA
  • Patients with either measurable disease as defined by RECIST criteria or bone only disease are eligible; Note: those patients with both non-measurable disease and bone metastases are eligible
  • Non-measurable bone only disease: Non-measurable bone only disease may include any of the following: blastic bone lesions, lytic bone lesions without a measurable soft-tissue component, or mixed lytic-blastic bone lesions without a measurable soft-tissue component
  • Lytic bone lesions, with an identifiable soft tissue component, evaluated by computed tomography (CT) or magnetic resonance imaging (MRI), can be considered as measurable lesions if the soft tissue component otherwise meets the definition of measurability previously described
  • No tumors involving spinal cord or heart
  • No visceral crisis, lymphangitic spread or known brain metastases: visceral crisis is not the mere presence of visceral metastases, but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease
  • Histologic confirmation, from the A011203 pre-registration biopsy, by institutional/local pathologist of either locally advanced or metastatic breast cancer that is estrogen receptor positive and HER2 negative; those patients with bone only disease with either no tumor or insufficient tumor for ER/progesterone receptor (PR) and HER2 staining after the bone biopsy are still eligible to participate in this study
  • Estrogen receptor positive disease is defined as > 10% nuclear staining
  • HER2 negative disease as per 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines, one of the following must apply:
  • 0 or 1+ by immunohistochemistry (IHC) and not amplified by in situ hybridization (ISH)
  • 0 or 1+ by IHC and ISH not done
  • 2+ by IHC and not amplified by ISH or
  • IHC not done and not amplified by ISH
  • None of the following therapies are allowed prior to registration:
  • Chemotherapy =< 2 weeks
  • Immunotherapy =< 2 weeks
  • Biologic therapy =< 2 weeks
  • Hormonal therapy =< 2 weeks
  • Monoclonal antibodies =< 2 weeks
  • Radiation therapy =< 2 weeks
  • Anti-Her-2 or other "targeted" (e.g. mammalian target of rapamycin [mTOR]) therapy =< 2 weeks
  • NOTE : Any toxicities derived from these therapies must be =< grade 2 prior to starting study therapy

Who cannot join

None listed.

Trial locations and contacts

559 sites in 1 country.

300 sites in 1 country

United States300 sites

  • Pali Momi Medical Center

    ‘Aiea, Hawaii, 96701

  • Queen's Cancer Center - Pearlridge

    ‘Aiea, Hawaii, 96701

  • The Cancer Center of Hawaii-Pali Momi

    ‘Aiea, Hawaii, 96701

  • Providence Regional Cancer System-Aberdeen

    Aberdeen, Washington, 98520

  • Jefferson Abington Hospital

    Abington, Pennsylvania, 19001

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Community Hospital of Anaconda

    Anaconda, Montana, 59711

  • Cancer Care Center at Island Hospital

    Anacortes, Washington, 98221

  • Kaiser Permanente-Anaheim

    Anaheim, California, 92806

  • Anchorage Associates in Radiation Medicine

    Anchorage, Alaska, 98508

  • Anchorage Radiation Therapy Center

    Anchorage, Alaska, 99504

  • Alaska Breast Care and Surgery LLC

    Anchorage, Alaska, 99508

  • Alaska Oncology and Hematology LLC

    Anchorage, Alaska, 99508

  • Alaska Regional Hospital

    Anchorage, Alaska, 99508

  • Alaska Women's Cancer Care

    Anchorage, Alaska, 99508

  • Anchorage Oncology Centre

    Anchorage, Alaska, 99508

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • PCR Oncology

    Arroyo Grande, California, 93420

  • AdventHealth Infusion Center Asheville

    Asheville, North Carolina, 28803

  • University Cancer and Blood Center LLC

    Athens, Georgia, 30607

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Sutter Auburn Faith Hospital

    Auburn, California, 95602

  • Sutter Cancer Centers Radiation Oncology Services-Auburn

    Auburn, California, 95603

  • MultiCare Auburn Medical Center

    Auburn, Washington, 98001

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Virginia Mason Bainbridge Island Medical Center

    Bainbridge Island, Washington, 98110

  • Saint Alphonsus Cancer Care Center-Baker City

    Baker City, Oregon, 97814

  • AIS Cancer Center at San Joaquin Community Hospital

    Bakersfield, California, 93301

  • Kaiser Permanente-Baldwin Park

    Baldwin Park, California, 91706

  • Mercy Oncology and Hematology - Clayton-Clarkson

    Ballwin, Missouri, 63011

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • CommonSpirit Saint Joseph Hospital - Bardstown

    Bardstown, Kentucky, 40004

  • Ochsner Health Center-Summa

    Baton Rouge, Louisiana, 70809

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Overlake Medical Center

    Bellevue, Washington, 98004

  • Swedish Cancer Institute-Eastside Oncology Hematology

    Bellevue, Washington, 98005

  • Kaiser Permanente-Bellflower

    Bellflower, California, 90706

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Gaston Hematology and Oncology Associates-Belmont

    Belmont, North Carolina, 28012

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • OSF Saint Joseph Medical Center

    Bloomington, Illinois, 61701

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Parkland Health Center-Bonne Terre

    Bonne Terre, Missouri, 63628

  • McFarland Clinic - Boone

    Boone, Iowa, 50036

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Cox Cancer Center Branson

    Branson, Missouri, 65616

  • Lafayette Family Cancer Center-EMMC

    Brewer, Maine, 04412

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • State University of New York Downstate Medical Center

    Brooklyn, New York, 11203

  • Saint Joseph Regional Cancer Center

    Bryan, Texas, 77802

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Saint Anne Hospital

    Burien, Washington, 98166

  • Mills-Peninsula Medical Center

    Burlingame, California, 94010

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park

    Cameron Park, California, 95682

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Trinity Health IHA Medical Group Hematology Oncology - Canton

    Canton, Michigan, 48188

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

  • Cleveland Clinic Mercy Hospital

    Canton, Ohio, 44708

  • Aultman Health Foundation

    Canton, Ohio, 44710

  • Mercy Cancer Center - Cape Girardeau

    Cape Girardeau, Missouri, 63703

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Memorial Hospital of Carbondale

    Carbondale, Illinois, 62902

  • Caro Cancer Center

    Caro, Michigan, 48723

  • Carson Tahoe Regional Medical Center

    Carson City, Nevada, 89703

  • SIH Cancer Institute

    Carterville, Illinois, 62918

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Waverly Hematology Oncology

    Cary, North Carolina, 27518

  • Eden Hospital Medical Center

    Castro Valley, California, 94546

  • Dayton Physicians LLC-Miami Valley South

    Centerville, Ohio, 45459

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • Cancer Center of Kansas - Chanute

    Chanute, Kansas, 66720

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Roper Hospital

    Charleston, South Carolina, 29401

  • Charleston Oncology - Roper

    Charleston, South Carolina, 29403

  • Lowcountry Hematology Oncology PA-North Charleston

    Charleston, South Carolina, 29406

  • Bon Secours Saint Francis Hospital

    Charleston, South Carolina, 29414

  • Charleston Oncology - Saint Francis

    Charleston, South Carolina, 29414

  • Lowcountry Oncology Associates - West Ashley

    Charleston, South Carolina, 29414

  • Memorial Hospital

    Chattanooga, Tennessee, 37404

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Northwestern University

    Chicago, Illinois, 60611

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • UChicago Medicine Comprehensive Cancer Center - Saint Joseph Hospital

    Chicago, Illinois, 60657

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Oncology Hematology Care Inc-Eden Park

    Cincinnati, Ohio, 45202

  • Oncology Hematology Care Inc-Mercy West

    Cincinnati, Ohio, 45211

  • Good Samaritan Hospital - Cincinnati

    Cincinnati, Ohio, 45220

  • Oncology Hematology Care Inc-Anderson

    Cincinnati, Ohio, 45230

  • Oncology Hematology Care Inc-Kenwood

    Cincinnati, Ohio, 45236

  • Bethesda North Hospital

    Cincinnati, Ohio, 45242

  • Oncology Hematology Care Inc-Blue Ash

    Cincinnati, Ohio, 45242

  • TriHealth Cancer Institute-Westside

    Cincinnati, Ohio, 45247

  • TriHealth Cancer Institute-Anderson

    Cincinnati, Ohio, 45255

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Hematology Oncology Consultants-Clarkston

    Clarkston, Michigan, 48346

  • Newland Medical Associates-Clarkston

    Clarkston, Michigan, 48346

  • Sampson Radiation Oncology

    Clinton, North Carolina, 28328

  • Southeastern Medical Oncology Center-Clinton

    Clinton, North Carolina, 28328

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Big Horn Basin Cancer Center

    Cody, Wyoming, 82414

  • Billings Clinic-Cody

    Cody, Wyoming, 82414

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • Rocky Mountain Cancer Centers-Penrose

    Colorado Springs, Colorado, 80907

  • MU Health - University Hospital/Ellis Fischel Cancer Center

    Columbia, Missouri, 65212

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Mount Carmel East Hospital

    Columbus, Ohio, 43213

  • Columbus Oncology and Hematology Associates Inc

    Columbus, Ohio, 43214

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Grant Medical Center

    Columbus, Ohio, 43215

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

  • Mount Carmel Health Center West

    Columbus, Ohio, 43222

  • Doctors Hospital

    Columbus, Ohio, 43228

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • Baptist Health Corbin

    Corbin, Kentucky, 40701

  • Commonwealth Cancer Center-Corbin

    Corbin, Kentucky, 40701

  • Alegent Health Mercy Hospital

    Council Bluffs, Iowa, 51503

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • Oncology Hematology Care Inc-Crestview

    Crestview Hills, Kentucky, 41017

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Northside Hospital-Forsyth

    Cumming, Georgia, 30041

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Sutter Davis Hospital

    Davis, California, 95616

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Dayton Physician LLC - Englewood

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Halifax Health Cancer Center for Hope - Daytona Beach

    Daytona Beach, Florida, 32114

  • Corewell Health Dearborn Hospital

    Dearborn, Michigan, 48124

  • Emory Decatur Hospital

    Decatur, Georgia, 30033

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

  • Delaware Radiation Oncology

    Delaware, Ohio, 43015

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • AdventHealth Porter

    Denver, Colorado, 80210

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan, 48236

  • Cancer Center of Kansas - Dodge City

    Dodge City, Kansas, 67801

  • Doylestown Hospital

    Doylestown, Pennsylvania, 18901

  • Epic Care-Dublin

    Dublin, California, 94568

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • CommonSpirit Cancer Center Mercy

    Durango, Colorado, 81301

  • Mercy Medical Center

    Durango, Colorado, 81301

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Henry Ford River District Hospital

    East China Township, Michigan, 48054

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Cancer Center of Kansas - El Dorado

    El Dorado, Kansas, 67042

  • Baptist Health Hardin

    Elizabethtown, Kentucky, 42701

  • Ascension Alexian Brothers - Elk Grove Village

    Elk Grove Village, Illinois, 60007

  • Christiana Care - Union Hospital

    Elkton, Maryland, 21921

  • Bay Area Breast Surgeons Inc

    Emeryville, California, 94608

  • Epic Care Partners in Cancer Care

    Emeryville, California, 94608

  • Walter Knox Memorial Hospital

    Emmett, Idaho, 83617

  • Saint Elizabeth Hospital

    Enumclaw, Washington, 98022

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Fairbanks Memorial Hospital

    Fairbanks, Alaska, 99701

  • JCHC McCreery Cancer Center

    Fairfield, Iowa, 52556

  • Oncology Hematology Care Inc-Healthplex

    Fairfield, Ohio, 45014

  • Essentia Health Cancer Center-South University Clinic

    Fargo, North Dakota, 58103

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Virginia Mason Federal Way Medical Center

    Federal Way, Washington, 98002

  • Saint Francis Hospital

    Federal Way, Washington, 98003

  • Lake Region Healthcare Corporation-Cancer Care

    Fergus Falls, Minnesota, 56537

  • Armes Family Cancer Center

    Findlay, Ohio, 45840

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Orion Cancer Care

    Findlay, Ohio, 45840

  • Cancer Hematology Centers - Flint

    Flint, Michigan, 48503

  • Genesee Hematology Oncology PC

    Flint, Michigan, 48503

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Kaiser Permanente-Fontana

    Fontana, California, 92335

  • McFarland Clinic - Trinity Cancer Center

    Fort Dodge, Iowa, 50501

  • Cancer Center of Kansas - Fort Scott

    Fort Scott, Kansas, 66701

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Western Illinois Cancer Treatment Center

    Galesburg, Illinois, 61401

  • CaroMont Regional Medical Center

    Gastonia, North Carolina, 28054

  • Gaston Hematology and Oncology Associates

    Gastonia, North Carolina, 28054

  • Tacoma/Valley Radiation Oncology Centers-Gig Harbor

    Gig Harbor, Washington, 98332

  • MultiCare Gig Harbor Medical Park

    Gig Harbor, Washington, 98335

  • Mountain Blue Cancer Care Center

    Golden, Colorado, 80401

  • Southeastern Medical Oncology Center-Goldsboro

    Goldsboro, North Carolina, 27534

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • Wayne Radiation Oncology

    Goldsboro, North Carolina, 27534

  • Altru Cancer Center

    Grand Forks, North Dakota, 58201

  • Nebraska Cancer Specialists/Oncology Hematology West PC

    Grand Island, Nebraska, 68803

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Great Falls Clinic

    Great Falls, Montana, 59405

  • Dayton Physicians LLC-Wayne

    Greenville, Ohio, 45331

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • Saint Francis Cancer Center

    Greenville, South Carolina, 29607

  • Self Regional Healthcare

    Greenwood, South Carolina, 29646

  • Henry Ford Saint John Hospital - Academic

    Grosse Pointe Woods, Michigan, 48236

  • Henry Ford Saint John Hospital - Breast

    Grosse Pointe Woods, Michigan, 48236

  • Henry Ford Saint John Hospital - Van Elslander

    Grosse Pointe Woods, Michigan, 48236

  • Kaiser Permanente South Bay

    Harbor City, California, 90710

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • Geisinger Medical Center-Cancer Center Hazleton

    Hazleton, Pennsylvania, 18201

  • Saint Peter's Community Hospital

    Helena, Montana, 59601

  • Cancer and Blood Specialists-Henderson

    Henderson, Nevada, 89052

  • Comprehensive Cancer Centers of Nevada - Henderson

    Henderson, Nevada, 89052

  • Las Vegas Cancer Center-Henderson

    Henderson, Nevada, 89052

  • Comprehensive Cancer Centers of Nevada-Southeast Henderson

    Henderson, Nevada, 89074

  • Oncology Las Vegas - Henderson

    Henderson, Nevada, 89074

  • Maria Parham Hospital

    Henderson, North Carolina, 27536

  • Margaret R Pardee Memorial Hospital

    Hendersonville, North Carolina, 28791

  • AdventHealth Hendersonville

    Hendersonville, North Carolina, 28792

  • Pulmonary Medicine Center of Chattanooga-Hixson

    Hixson, Tennessee, 37343

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Island Urology

    Honolulu, Hawaii, 96813

  • Queen's Cancer Cenrer - POB I

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Hawaii Cancer Care Inc-Liliha

    Honolulu, Hawaii, 96817

  • Kuakini Medical Center

    Honolulu, Hawaii, 96817

  • Queen's Cancer Center - Kuakini

    Honolulu, Hawaii, 96817

  • The Cancer Center of Hawaii-Liliha

    Honolulu, Hawaii, 96817

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • CHI Saint Vincent Cancer Center Hot Springs

    Hot Springs, Arkansas, 71913

  • Cancer Center of Kansas-Independence

    Independence, Kansas, 67301

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Sidney and Lois Eskenazi Hospital

    Indianapolis, Indiana, 46202

  • Springmill Medical Center

    Indianapolis, Indiana, 46290

  • Kaiser Permanente-Irvine

    Irvine, California, 92618

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • Allegiance Health

    Jackson, Michigan, 49201

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Onslow Memorial Hospital

    Jacksonville, North Carolina, 28546

  • Southeastern Medical Oncology Center-Jacksonville

    Jacksonville, North Carolina, 28546

  • McFarland Clinic - Jefferson

    Jefferson, Iowa, 50129

  • MU Health Care Goldschmidt Cancer Center

    Jefferson City, Missouri, 65109

  • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro

    Jonesboro, Arkansas, 72401

  • Freeman Health System

    Joplin, Missouri, 64804

  • Mercy Hospital Joplin

    Joplin, Missouri, 64804

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Beacon Kalamazoo

    Kalamazoo, Michigan, 49048

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • Fred and Pamela Buffett Cancer Center - Kearney

    Kearney, Nebraska, 68845

  • CHI Health Good Samaritan

    Kearney, Nebraska, 68847

  • Ochsner Medical Center Kenner

    Kenner, Louisiana, 70065

  • Greater Dayton Cancer Center

    Kettering, Ohio, 45409

  • First Dayton Cancer Care

    Kettering, Ohio, 45420

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • Cancer Center of Kansas-Kingman

    Kingman, Kansas, 67068

  • ECU Health Oncology Kinston

    Kinston, North Carolina, 28501

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Providence Regional Cancer System-Lacey

    Lacey, Washington, 98503

  • Northwell Health/Center for Advanced Medicine

    Lake Success, New York, 11042

  • CommonSpirit Saint Anthony Hospital Cancer Center

    Lakewood, Colorado, 80228

  • Rocky Mountain Cancer Centers-Lakewood

    Lakewood, Colorado, 80228

  • Saint Clare Hospital

    Lakewood, Washington, 98499

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

  • University of Michigan Health - Sparrow Lansing

    Lansing, Michigan, 48912

  • Cancer and Blood Specialists-Shadow

    Las Vegas, Nevada, 89106

Other trials in United States

About this study

Official title: A Randomized Phase II Trial of Tamoxifen Versus Z-Endoxifen HCL in Postmenopausal Women With Metastatic Estrogen Receptor Positive, HER2 Negative Breast Cancer

This randomized phase II trial studies how well tamoxifen citrate works compared with z-endoxifen hydrochloride in treating patients with breast cancer that has spread to nearby tissue or lymph nodes or other parts of the body and has estrogen receptors but not human epidermal growth factor receptor 2 (HER2) receptors on the surface of its cells. Estrogen can cause the growth of tumor cells. Hormone therapy using tamoxifen citrate or z-endoxifen hydrochloride may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether tamoxifen citrate or z-endoxifen hydrochloride is more effective in treating patients with breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess whether progression-free survival with z-endoxifen hydrochloride (HCl) relative to that with tamoxifen (tamoxifen citrate) is prolonged in postmenopausal women with local advanced or metastatic estrogen receptor (ER) positive/Her2 negative breast cancer.

SECONDARY OBJECTIVES:

  1. To assess the safety profile of each of these agents in this patient population.

II. To assess whether the tumor response rate (as determined using the Response Evaluation Criteria in Solid Tumors [RECIST] criteria) among those randomized to z-endoxifen HCl differs from that among those randomized to tamoxifen.

III. To estimate the median progression-free survival time for those who receive z-endoxifen HCl after disease progression with tamoxifen.

CORRELATIVE SCIENCE OBJECTIVES:

  1. To examine whether ER alpha alterations (defined as either ER activating mutations or ER amplification) are associated with longer progression-free survival (PFS) or higher response rates in the z-endoxifen HCl arm compared to the tamoxifen arm.

II. To determine changes in lipid profiles comparing tamoxifen and z-endoxifen HCl.

III. For each treatment, to evaluate changes in markers of bone formation and absorption after 12 weeks (4 cycles) of treatment.

IV. For all patients and by treatment arm, to determine whether progression-free survival differs with respect to the sensitive to endocrine therapy (SET) index.

  1. To examine whether deoxyribonucleic acid (DNA) alterations as measured by Foundation medicine in all coding exons of 287 cancer-related genes as well as 78 polymorphisms in 34 absorption, distribution, metabolism, and excretion (ADME)-related genes are associated with longer PFS or higher response rates in the z-endoxifen HCl arm compared to the tamoxifen arm.

VI. To assess whether the molecular characteristics identified in the tumor biopsies are detectable in the circulating tumor cells (CTCs) and/or cell-free DNA (cfDNA).

VII. For each treatment arm: to examine changes in ER expression on CTCs, changes in estrogen receptor (ESR) mutations or amplification in CTCs or CfDNA and explore the impact of these changes on PFS and response rates.

PHARMACOKINETICS AND PHARMACOGENOMICS OBJECTIVES:

  1. To further characterize pharmacokinetics, pharmacogenetics and metabolism of z-endoxifen HCl and tamoxifen.

II. To determine the impact of the concentrations of tamoxifen and its metabolites on PFS in the tamoxifen arm.

III. To determine the impact of the concentrations of z-endoxifen HCl and its metabolites on PFS in the endoxifen arm.

  1. To determine the impact of genetic variation in the enzymes responsible for tamoxifen and z-endoxifen HCl metabolism.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive z-endoxifen hydrochloride orally (PO) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive tamoxifen citrate PO once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression and bone metastases may cross over to Arm I and receive z-endoxifen hydrochloride starting no later than 28 days after documentation of disease progression.

After completion of study treatment, patients are followed up yearly for up to 5 years.

Being tested
Endoxifen Hydrochloride, Laboratory Biomarker Analysis, Pharmacological Study, Tamoxifen Citrate
Medical subject headings
Breast Neoplasms

What participants receive

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

  • Endoxifen HydrochlorideDrug

    Also called Z-Endoxifen HCl, Z-Endoxifen Hydrochloride

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • Tamoxifen CitrateDrug

    Also called Apo-Tamox, Clonoxifen, Dignotamoxi, Ebefen

    Given PO

Study groups in NCT02311933
Study groupRoleWhat they receive
Arm I (z-endoxifen hydrochloride)ExperimentalPatients receive z-endoxifen hydrochloride PO on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Endoxifen Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Arm II (tamoxifen citrate)ExperimentalPatients receive tamoxifen citrate PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression and bone metastases may cross over to Arm I and receive z-endoxifen hydrochloride starting no later than 28 days after documentation of disease progression.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Tamoxifen Citrate

What is being measured

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

  1. Progression Free Survival (PFS)

    The primary endpoint is progression-free survival (PFS) defined as the time from randomization to documentation of local, regional or distant disease progression or death without progression of disease.

    Measured: Assessed up to 5 years

Secondary outcomes (3)

  1. Incidence of Adverse Events, Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

    For a given adverse event (AE), the proportion of patients on each treatment arm who report developing a grade 2-5 of this AE will be determined.

    Measured: Up to 5 years

  2. Tumor Response Rate by Study Arm, Defined as the Number of Patients With a Complete or Partial Response

    Defined by Response Evaluation Criteria in Solid Tumors on 2 consecutive evaluations at least 6 weeks apart, divided by the total number of eligible patients who began study treatment. A 90% binomial confidence interval will be constructed for the true response rate.

    Measured: Up to 5 years

  3. Overall Survival Distribution by Study Arm

    The distribution of survival times will be estimated using the method of Kaplan-Meier.

    Measured: The time from registration to death due to any cause, assessed up to 5 years

Timeline

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

  1. First posted9 Dec 2014 (estimated)
  2. Study start28 May 2015
  3. Primary completion6 Nov 2020
  4. Study completion2 Feb 2027 (estimated)

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
Crossover
Masking
None (open label)
Enrolment
81 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02311933
Sponsor's protocol ID
NCI-2014-02409
Other IDs
NCI-2014-02409, A011203, A011203, A011203, U10CA180821
Status last verified
Aug 2026
First submitted
8 Dec 2014
Last updated
22 Oct 2026
Data monitoring committee
No

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