AzTrials
AzTrials

Breast Carcinoma In SituPhase 3NCT02954874

Testing MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer

A Phase 3 study testing Biospecimen Collection, Laboratory Biomarker Analysis and Patient Observation in people with Breast Carcinoma In Situ and Invasive Breast Carcinoma, run by National Cancer Institute (NCI) at 919 sites in 3 countries.

Active, not recruiting

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

Official record
Search all trials

Trial summary

This randomized phase III trial studies how well pembrolizumab works in treating patients with triple-negative breast cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Laboratory Biomarker Analysis and Patient Observation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,195 participants
Where
919 sitesin 3 countries
Study dates
18 Jan 2017to 27 Aug 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

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

  • STEP 1 REGISTRATION
  • Patients must have histologically confirmed estrogen receptor (ER)-, progesterone receptor (PR)- and HER2-negative (triple-negative, TNBC) or ER-, PR- weakly positive and/or HER2- equivocal status and must not have received and not be planning to receive adjuvant anti-HER2 or endocrine therapies after completion of neoadjuvant chemotherapy; patients who are HER2-positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines are ineligible; HER2-negative and HER2-equivocal cases as per ASCO CAP guidelines that do not receive HER2-targeted therapy are eligible; patients with weakly ER or PR positive disease, defined as ER and/or PR less than or equal to (=<) 5% by immunohistochemistry, are eligible if the treating physician considers the patient not eligible for adjuvant endocrine therapy; residual disease must be >= 1 cm in greatest dimension, and/or have positive lymph nodes (ypN1mi, ypN1, ypN2, ypN3) observed on pathologic exam
  • NOTE: If the ER and/or HER2 results are discordant between the initial, pre-chemotherapy, and post-chemotherapy surgical tissue, the receptor status of the residual disease has to be used to determine eligibility. Immunohistochemistry (IHC)-positive isolated tumor cells in the lymph node (N0 [i+]) are not considered node-positive and these patients also must have >= 1 cm residual invasive cancer in the breast to be eligible.
  • Patients must not have metastatic disease (i.e., must be clinically M0 or Mx; systemic staging studies with imaging should follow routine practice as per National Comprehensive Cancer Network [NCCN] and ASCO guidelines); patients must not have locally recurrent disease
  • It is preferred that axillary lymph node sampling is performed after completion of neoadjuvant chemotherapy to allow more accurate assessment of pathologic response; complete axillary lymph node dissection (ALND) after neoadjuvant chemotherapy is recommended in the following situations:
  • Patients had documented pathologic involvement of the axillary nodes (fine needle aspiration [FNA] or core biopsy) before neoadjuvant chemotherapy and had sentinel node biopsy after neoadjuvant chemotherapy with positive sentinel node(s)
Show all 47Show fewer
  • Patient had documented pathologic involvement of the axillary nodes (FNA or core biopsy) before neoadjuvant chemotherapy and had only 1 sentinel lymph node removed after neoadjuvant chemotherapy
  • Except for (i) patients participating in the Alliance A11202 trial) or (ii) if the treating surgeon determines that a complete ALND is not in the best interest of the patient
  • NOTE: Patients who undergo sentinel node biopsy before starting neoadjuvant treatment and do not undergo post neoadjuvant assessment of the axillary nodes or who have negative axillary nodes on post neoadjuvant assessment must have >= 1 cm residual invasive cancer in the breast after completion of neoadjuvant chemotherapy
  • Patients must have a minimum of five, available unstained formalin-fixed paraffin-embedded (FFPE) slides (4-5 micron thickness) from the residual (post-neoadjuvant) invasive tumor in primary site or lymph node; (these will be submitted to a central laboratory to determine PD-L1 expression); the tumor tissue must be adequate for PD-L1 testing, which typically requires a minimum of 100 cancer cells per slide; local PD-L1 results, even if available, will not substitute for central testing
  • NOTE: Initial order for specimen kits should be placed at least two weeks prior to registering the first patient at each site
  • Patients must be offered the opportunity to participate in specimen banking
  • The BAHO substudy was permanently closed to accrual on June 23, 2020, and willingness of English-speaking patients to participate in the BAHO substudy is no longer applicable
  • Patients must have had neoadjuvant chemotherapy followed by surgery; the choice of neoadjuvant chemotherapy is determined by the treating physician; we recommend following the National Comprehensive Cancer Network (NCCN) treatment guidelines for TNBC; patients who cannot complete all planned treatment cycles for any reason are considered high risk and therefore are eligible for the study if they have residual disease; patients must have resolution of adverse event(s) of the most recent prior chemotherapy to grade 1 or less, except alopecia and =< grade 2 neuropathy which are allowed
  • Patients may receive post-operative (adjuvant) chemotherapy for up to 24 weeks of duration (e.g. 8 cycles of capecitabine as in the Capecitabine for Residual Cancer as Adjuvant Therapy (CREATE-X) trial; the 24-week duration does not include treatment delays) after completion of surgery at the discretion of the treating physician; co-enrollment to EA1131 is allowed, provided that patients complete or discontinue adjuvant chemotherapy prior to step 1 registration; at the time of step 1 registration, patients must have resolution of adverse event(s) of the most recent prior chemotherapy to =< grade 1, except alopecia and =< grade 2 neuropathy which are allowed; patients that have received adjuvant chemotherapy (including via co-enrollment to EA1131) must be registered to step 1 within 35 days after final dose of adjuvant chemotherapy
  • Patients must have completed their final breast surgery (rendering them free from disease) with clear resection margins for invasive cancer and DCIS within the following timelines:
  • 90 days prior to step 1 screening registration for patients not receiving post-operative (adjuvant) chemotherapy OR
  • 270 days prior to step 1 screening registration for patients who have received post-operative (adjuvant) chemotherapy Positive margins are allowed only if the surgical team of the patient deems further resection impossible
  • Patients for whom radiation therapy (RT) to the affected breast or chest wall and regional nodal areas is clinically indicated as per NCCN treatment guidelines, should receive routine RT after randomization when possible, and receive MK-3475 (pembrolizumab) concurrent with RT, if randomized to the experimental arm; however, routine RT administered, or initiated, prior to registration is also allowed; MK-3475 (pembrolizumab) may be added to ongoing radiation, or started after its completion, if randomized to the experimental arm, provided there are no > grade 1 radiation-related skin toxicities and provided that no radiosensitizing chemotherapy is being administered; co-enrollment in the Alliance A221505 (NCT03414970) and A011202 (NCT01901094) trials or in the NSABP-B51 (NCT01872975) trial is allowed, but patients must not be planning to receive radiation therapy given on these trials concurrently with MK-3475 (pembrolizumab) treatment on S1418/BR006; whether or not patient will receive RT and the extent of intended RT must be specified at time of registration; NOTE: Patients who receive post-operative chemotherapy may receive radiation therapy before or after the chemotherapy; a short course of reduced dose chemotherapy or other agents concomitant with radiation for radiation sensitization is not considered to be adjuvant chemotherapy
  • Patients must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti-CTLA4 or similar drugs; patients must not be planning to receive any of the prohibited therapies during the screening or treatment phases of the study
  • Patients must not be planning to receive concomitantly other biologic therapy, hormonal therapy, other chemotherapy, surgery or other anti-cancer therapy except radiation therapy while receiving treatment on this protocol; however, patients receiving extended adjuvant endocrine therapy for an earlier ER positive breast cancer treated with curative intent and without recurrence for at least 5 years may continue with their endocrine therapy; elective surgery or surgery that is not related to cancer therapy is allowed, at the discretion of the treating investigator
  • Patients must be >= 18 years of age
  • Patients must have Zubrod performance status =< 2
  • Patients must not have a history of (non-infectious) pneumonitis that required steroids or evidence of active pneumonitis within 2 years prior to registration
  • Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine for pre-existing hypothyroidism, insulin for type I diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Patients must not have received live vaccines within 30 days prior to registration; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
  • Patients must not have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection prior to registration; patients who have completed curative therapy for HCV are eligible; patients with known human immunodeficiency virus (HIV) infection are eligible if they meet each of the following 3 criteria:
  • CD4 counts >= 350 mm^3
  • Serum HIV viral load of < 25,000 IU/ml and
  • Treated on a stable antiretroviral regimen
  • No other prior invasive malignancy is allowed except for the following: adequately treated basal (or squamous cell) skin cancer, in situ breast or cervical cancer; stage I or II invasive cancer treated with a curative intent without evidence of disease recurrence for at least five years
  • Patients must have complete history and physical examination within 28 days prior to registration
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent for this protocol in accordance with institutional and federal guidelines
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • STEP 2 REGISTRATION
  • Patients must not be registered to step 2 until receiving confirmation from the Southwest Oncology Group (SWOG) Statistical and Data Management Center that the patient's tissue specimen was adequate for PD-L1 testing; patients must be registered within 14 days of receiving the e-mail notification confirming submission was evaluable for PD-L1 status
  • Absolute neutrophil count (ANC) >= 1,500 microliter (mcL) (obtained within 28 days prior to step 2 registration)
  • Platelets >= 100,000/mcL (obtained within 28 days prior to step 2 registration)
  • Hemoglobin >= 9 g/dL (obtained within 28 days prior to step 2 registration)
  • A serum thyroid-stimulating hormone (TSH) and/or free T4 must be obtained within 28 days prior to step 2 registration to obtain a baseline value
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (obtained within 28 days prior to step 2 registration)
  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x IULN (obtained within 28 days prior to step 2 registration)
  • Alkaline phosphatase =< 2.5 x IULN (obtained within 28 days prior to step 2 registration)
  • Serum creatinine =< IULN OR measured or calculated creatinine clearance >= 60 mL/min (obtained within 28 days prior to step 2 registration)
  • Women of childbearing potential must have a negative urine or serum pregnancy test within 28 day prior to registration; women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or vasectomy; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures; patients must not be pregnant or nursing; women of childbearing potential must plan to have a urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a negative serum pregnancy test will be required
  • Patients must not have an active infection requiring systemic therapy at the time of starting therapy
  • Site must verify that there is no known change in the step 1 eligibility since initial registration

Who cannot join

None listed.

Trial locations and contacts

919 sites in 3 countries.

324 sites in 3 countries

United States300 sites

  • Hawaii Cancer Care - Westridge

    ‘Aiea, Hawaii, 96701

  • Providence Regional Cancer System-Aberdeen

    Aberdeen, Washington, 98520

  • Jefferson Abington Hospital

    Abington, Pennsylvania, 19001

  • Summa Health System - Akron Campus

    Akron, Ohio, 44304

  • Phoebe Putney Memorial Hospital

    Albany, Georgia, 31701

  • Atrium Health Stanly/LCI-Albemarle

    Albemarle, North Carolina, 28002

  • Lovelace Medical Center-Saint Joseph Square

    Albuquerque, New Mexico, 87102

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • New Mexico Oncology Hematology Consultants

    Albuquerque, New Mexico, 87109

  • Presbyterian Kaseman Hospital

    Albuquerque, New Mexico, 87110

  • Christus Saint Frances Cabrini Hospital

    Alexandria, Louisiana, 71301

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • AdventHealth Altamonte

    Altamonte Springs, Florida, 32701

  • The Don and Sybil Harrington Cancer Center

    Amarillo, Texas, 79106

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Community Hospital of Anaconda

    Anaconda, Montana, 59711

  • Kaiser Permanente-Anaheim

    Anaheim, California, 92806

  • Alaska Oncology and Hematology LLC

    Anchorage, Alaska, 99508

  • Anchorage Oncology Centre

    Anchorage, Alaska, 99508

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • AnMed Health Cancer Center

    Anderson, South Carolina, 29621

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • Luminis Health Anne Arundel Medical Center

    Annapolis, Maryland, 21401

  • Aspirus Cancer Care-Antigo-Volm Cancer Center

    Antigo, Wisconsin, 54409

  • Kaiser Permanente-Deer Valley Medical Center

    Antioch, California, 94531

  • ThedaCare Regional Cancer Center

    Appleton, Wisconsin, 54911

  • Ascension Northeast Wisconsin-Saint Elizabeth Cancer Center-Appleton

    Appleton, Wisconsin, 54915

  • Northwest Community Hospital

    Arlington Heights, Illinois, 60005

  • PCR Oncology

    Arroyo Grande, California, 93420

  • Randolph Hospital

    Asheboro, North Carolina, 27203

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Messino Cancer Centers

    Asheville, North Carolina, 28806

  • Hope Women's Cancer Centers-Asheville

    Asheville, North Carolina, 28816

  • Duluth Clinic Ashland

    Ashland, Wisconsin, 54806

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Sutter Auburn Faith Hospital

    Auburn, California, 95602

  • Augusta Oncology Associates PC-D'Antignac

    Augusta, Georgia, 30901

  • Augusta Oncology Associates PC-Wheeler

    Augusta, Georgia, 30909

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • Rocky Mountain Cancer Centers-Aurora

    Aurora, Colorado, 80012

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Dell Seton Medical Center at The University of Texas

    Austin, Texas, 78701

  • Austin Cancer Centers-Central Austin

    Austin, Texas, 78702

  • 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

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Mercy Medical Center

    Baltimore, Maryland, 21202

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Saint Agnes Hospital

    Baltimore, Maryland, 21229

  • MedStar Franklin Square Medical Center/Weinberg Cancer Institute

    Baltimore, Maryland, 21237

  • MedStar Good Samaritan Hospital

    Baltimore, Maryland, 21239

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • CommonSpirit Saint Joseph Hospital - Bardstown

    Bardstown, Kentucky, 40004

  • LSU Health Baton Rouge-North Clinic

    Baton Rouge, Louisiana, 70805

  • Our Lady of the Lake Physician Group

    Baton Rouge, Louisiana, 70808

  • Hematology/Oncology Clinic PLLC

    Baton Rouge, Louisiana, 70809

  • Louisiana Hematology Oncology Associates LLC

    Baton Rouge, Louisiana, 70809

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • Ochsner Health Center-Summa

    Baton Rouge, Louisiana, 70809

  • Medical Center of Baton Rouge

    Baton Rouge, Louisiana, 70816

  • Woman's Hospital

    Baton Rouge, Louisiana, 70817

  • Ochsner High Grove

    Baton Rouge, Louisiana, 70836

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • McLaren Cancer Institute-Bay City

    Bay City, Michigan, 48706

  • Houston Methodist San Jacinto Hospital

    Baytown, Texas, 77521

  • Cleveland Clinic Cancer Center Beachwood

    Beachwood, Ohio, 44122

  • UHHS-Chagrin Highlands Medical Center

    Beachwood, Ohio, 44122

  • Indu and Raj Soin Medical Center

    Beavercreek, Ohio, 45431

  • UM Upper Chesapeake Medical Center

    Bel Air, Maryland, 21014

  • MaineHealth Waldo Hospital

    Belfast, Maine, 04915

  • Overlake Medical Center

    Bellevue, Washington, 98004

  • Kaiser Permanente-Bellflower

    Bellflower, California, 90706

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Mac Neal Hospital

    Berwyn, Illinois, 60402

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • University of Iowa Healthcare Cancer Services Quad Cities

    Bettendorf, Iowa, 52722

  • MaineHealth Maine Medical Center - Biddeford

    Biddeford, Maine, 04005

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Saint Joseph's/Candler - Bluffton Campus

    Bluffton, South Carolina, 29910

  • Prisma Health Cancer Institute - Spartanburg

    Boiling Springs, South Carolina, 29316

  • 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

  • McFarland Clinic - Boone

    Boone, Iowa, 50036

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Rocky Mountain Cancer Centers-Boulder

    Boulder, Colorado, 80304

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Lafayette Family Cancer Center-EMMC

    Brewer, Maine, 04412

  • Ocean University Medical Center

    Brick, New Jersey, 08724

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • Ballad Health Cancer Care - Bristol

    Bristol, Virginia, 24201

  • Ascension Southeast Wisconsin Hospital-Elmbrook Campus-Brookfield

    Brookfield, Wisconsin, 53045

  • New York-Presbyterian/Brooklyn Methodist Hospital

    Brooklyn, New York, 11215

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Mills-Peninsula Medical Center

    Burlingame, California, 94010

  • Lahey Clinic

    Burlington, Massachusetts, 01805

  • Cone Health Cancer Center at Alamance Regional

    Burlington, North Carolina, 27215

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Minnesota Oncology - Burnsville

    Burnsville, Minnesota, 55337

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • 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

  • IU Health North Hospital

    Carmel, Indiana, 46032

  • Caro Cancer Center

    Caro, Michigan, 48723

  • SIH Cancer Institute

    Carterville, Illinois, 62918

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Physicians' Clinic of Iowa PC

    Cedar Rapids, Iowa, 52402

  • Mercy Hospital

    Cedar Rapids, Iowa, 52403

  • Oncology Associates at Mercy Medical Center

    Cedar Rapids, Iowa, 52403

  • AdventHealth Celebration

    Celebration, Florida, 34747

  • Dayton Physicians LLC-Miami Valley 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

  • Geauga Hospital

    Chardon, Ohio, 44024

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • Oncology Specialists of Charlotte

    Charlotte, North Carolina, 28207

  • Atrium Health Pineville/LCI-Pineville

    Charlotte, North Carolina, 28210

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Mount Sinai Hospital Medical Center

    Chicago, Illinois, 60608

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Weiss Memorial Hospital

    Chicago, Illinois, 60640

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Ascension Calumet Hospital-Chilton

    Chilton, Wisconsin, 53014

  • The Christ Hospital

    Cincinnati, Ohio, 45219

  • Good Samaritan Hospital - Cincinnati

    Cincinnati, Ohio, 45220

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Hematology Oncology Consultants-Clarkston

    Clarkston, Michigan, 48346

  • McLaren Cancer Institute-Clarkston

    Clarkston, Michigan, 48346

  • Newland Medical Associates-Clarkston

    Clarkston, Michigan, 48346

  • Morton Plant Hospital

    Clearwater, Florida, 33756

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Southeastern Medical Oncology Center-Clinton

    Clinton, North Carolina, 28328

  • Prisma Health Cancer Institute - Laurens

    Clinton, South Carolina, 29325

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

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

    Clive, Iowa, 50325

  • Community Cancer Institute

    Clovis, California, 93611

  • Billings Clinic-Cody

    Cody, Wyoming, 82414

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Baptist Memorial Hospital and Cancer Center-Collierville

    Collierville, Tennessee, 38017

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • Memorial Hospital North

    Colorado Springs, Colorado, 80920

  • Baptist Memorial Hospital and Cancer Center-Golden Triangle

    Columbus, Mississippi, 39705

  • 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

  • New Hampshire Oncology Hematology PA-Concord

    Concord, New Hampshire, 03301

  • Atrium Health Cabarrus/LCI-Concord

    Concord, North Carolina, 28025

  • UT MD Anderson - The Woodlands

    Conroe, Texas, 77384

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Baptist Health Corbin

    Corbin, Kentucky, 40701

  • City of Hope Corona

    Corona, California, 92882

  • Good Samaritan Hospital

    Corvallis, Oregon, 97330

  • UC Irvine Health Cancer Center-Newport

    Costa Mesa, California, 92627

  • Northshore Oncology Associates-Covington

    Covington, Louisiana, 70433

  • Ochsner Hematology Oncology North Shore - Covington (West Region)

    Covington, Louisiana, 70433

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • Danbury Hospital

    Danbury, Connecticut, 06810

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Southern Cancer Center PC-Daphne

    Daphne, Alabama, 36526

  • MercyOne Genesis Davenport Medical Center

    Davenport, Iowa, 52803

  • MercyOne Genesis Davenport Cancer Center

    Davenport, Iowa, 52804

  • Iowa Cancer Specialists

    Davenport, Iowa, 52807

  • Halifax Health Cancer Center for Hope - Daytona Beach

    Daytona Beach, Florida, 32114

  • Corewell Health Dearborn Hospital

    Dearborn, Michigan, 48124

  • Henry Ford Medical Center-Fairlane

    Dearborn, Michigan, 48126

  • Emory Decatur Hospital

    Decatur, Georgia, 30033

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Essentia Health - Deer River Clinic

    Deer River, Minnesota, 56636

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Kaiser Permanente-Franklin

    Denver, Colorado, 80205

  • National Jewish Health-Main Campus

    Denver, Colorado, 80206

  • AdventHealth Porter

    Denver, Colorado, 80210

  • Rocky Mountain Cancer Centers-Midtown

    Denver, Colorado, 80218

  • Saint Joseph Hospital - Cancer Centers of Colorado

    Denver, Colorado, 80218

  • Rocky Mountain Cancer Centers-Rose

    Denver, Colorado, 80220

  • Smilow Cancer Hospital-Derby Care Center

    Derby, Connecticut, 06418

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

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

    Des Moines, Iowa, 50309

  • Broadlawns Medical Center

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan, 48236

  • Cancer Center of Kansas - Dodge City

    Dodge City, Kansas, 67801

  • Doylestown Hospital

    Doylestown, Pennsylvania, 18901

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Epic Care-Dublin

    Dublin, California, 94568

  • Northside Hospital - Duluth

    Duluth, Georgia, 30096

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Prisma Health Cancer Institute - Easley

    Easley, South Carolina, 29640

  • Henry Ford River District Hospital

    East China Township, Michigan, 48054

  • Michigan State University

    East Lansing, Michigan, 48823

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Trinitas Hospital and Comprehensive Cancer Center - Williamson Street Campus

    Elizabeth, New Jersey, 07207

  • Arnot Ogden Medical Center/Falck Cancer Center

    Elmira, New York, 14905

  • Mercy Cancer Center-Elyria

    Elyria, Ohio, 44035

  • Bay Area Breast Surgeons Inc

    Emeryville, California, 94608

  • Epic Care Partners in Cancer Care

    Emeryville, California, 94608

  • Walter Knox Memorial Hospital

    Emmett, Idaho, 83617

  • Mountain Blue Cancer Care Center - Swedish

    Englewood, Colorado, 80113

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • Saint Vincent Hospital

    Erie, Pennsylvania, 16544

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Deaconess Clinic Downtown

    Evansville, Indiana, 47713

  • Fairbanks Memorial Hospital

    Fairbanks, Alaska, 99701

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

  • Smilow Cancer Hospital Care Center-Fairfield

    Fairfield, Connecticut, 06824

  • 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

  • Farmington Health Center

    Farmington, Utah, 84025

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • Corewell Health Farmington Hills Hospital

    Farmington Hills, Michigan, 48336

  • Augusta Health Center for Cancer and Blood Disorders

    Fishersville, Virginia, 22939

  • 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

  • McLaren Cancer Institute-Flint

    Flint, Michigan, 48532

  • Singh and Arora Hematology Oncology PC

    Flint, Michigan, 48532

  • McLeod Regional Medical Center

    Florence, South Carolina, 29506

  • Aurora Health Center-Fond du Lac

    Fond du Lac, Wisconsin, 54937

  • Kaiser Permanente-Fontana

    Fontana, California, 92335

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Cancer Care and Hematology-Fort Collins

    Fort Collins, Colorado, 80528

  • McFarland Clinic - Trinity Cancer Center

    Fort Dodge, Iowa, 50501

  • UI Healthcare Mission Cancer and Blood - Fort Dodge

    Fort Dodge, Iowa, 50501

  • Cancer Center of Kansas - Fort Scott

    Fort Scott, Kansas, 66701

  • Parkview Regional Medical Center

    Fort Wayne, Indiana, 46845

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Vanderbilt-Ingram Cancer Center Cool Springs

    Franklin, Tennessee, 37067

  • Reiman Cancer Center-Ascension Wisconsin Health Center-Rawson

    Franklin, Wisconsin, 53132

  • Frederick Memorial Hospital

    Frederick, Maryland, 21701

  • FMH James M Stockman Cancer Institute

    Frederick, Maryland, 21702

  • Freeport Memorial Hospital/Leonard C Ferguson Cancer Center

    Freeport, Illinois, 61032

  • Kaiser Permanente-Fremont

    Fremont, California, 94538

  • Palo Alto Medical Foundation-Fremont

    Fremont, California, 94538

  • Washington Health

    Fremont, California, 94538

  • Kaiser Permanente-Fresno

    Fresno, California, 93720

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

Other trials in United States

Canada20 sites

  • Arthur J E Child Comprehensive Cancer Centre

    Calgary, Alberta, T2N 5G2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • Waterloo Regional Health Network

    Kitchener, Ontario, N2G 1G3

  • Hopital de la Cite-de-la-Sante

    Laval, Quebec, H7M 3L9

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • The Moncton Hospital

    Moncton, New Brunswick, E1C 6Z8

  • The Research Institute of the McGill University Health Centre (MUHC)

    Montreal, Quebec, H3H 2R9

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Hopital Du Sacre-Coeur de Montreal

    Montreal, Quebec, H4J 1C5

  • Stronach Regional Health Centre at Southlake

    Newmarket, Ontario, L3Y 2P9

  • CHU de Quebec-Hopital du Saint-Sacrement (HSS)

    Québec, Quebec, G1S 4L8

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Atlantic Health Sciences Corporation-Saint John Regional Hospital

    Saint John, New Brunswick, E2L 4L2

  • Algoma District Cancer Program Sault Area Hospital

    Sault Ste. Marie, Ontario, P6B 0A8

  • Doctor H. Bliss Murphy Cancer Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

  • BCCA-Fraser Valley Cancer Centre

    Surrey, British Columbia, V3V 1Z2

  • Humber River Hospital

    Toronto, Ontario, M3M 0B2

  • Odette Cancer Centre- Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • BCCA-Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Puerto Rico4 sites

  • Cancer Center-Metro Medical Center Bayamon

    Bayamón, 00959-5060

  • Doctors Cancer Center

    Manati, 00674

  • San Juan Community Oncology Group

    San Juan, 00917

  • San Juan City Hospital

    San Juan, 00936

Other trials in Puerto Rico

About this study

Official title: A Randomized, Phase III Trial to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer With &gt;/= 1 CM Residual Invasive Cancer or Positive Lymph Nodes (ypN1mi, ypN1-3) After Neoadjuvant Chemotherapy

This randomized phase III trial studies how well pembrolizumab works in treating patients with triple-negative breast cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare invasive disease-free survival (IDFS) of patients with triple-negative (TNBC) or low estrogen receptor (ER)-positive and/or HER2 borderline breast cancer who have >= 1 cm residual invasive breast cancer and/or positive lymph nodes (ypN1mi, ypN1, ypN2, ypN3) after neoadjuvant chemotherapy randomized to receive 1 year of MK-3475 (pembrolizumab) adjuvant therapy compared to no MK-3475 (pembrolizumab), in both the entire study population and also in the PD-L1 positive subset.

SECONDARY OBJECTIVES:

  1. To compare the effects of MK-3475 (pembrolizumab) on overall survival (OS) and distant recurrence-free survival (DRFS) between the two randomized arms for the PD-L1 positive patients and then all patients.

II. To assess the toxicity and tolerability of MK-3475 (pembrolizumab) in this patient population with or without radiation therapy.

BEHAVIORAL AND HEALTH OUTCOMES (BAHO) STUDY OBJECTIVES:

  1. To examine the association between biomarkers of inflammation and quality of life and patient reported outcomes between the two groups during and at the end of therapy.

II. To examine the long-term and late effects of treatment on patient-reported outcomes.

ADDITIONAL OBJECTIVE:

  1. To collect tissue and whole blood for processing and banking in anticipation of future correlative studies in this patient population.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (OBSERVATION): Patients receive no treatment but are monitored at standard clinical intervals during first year after randomization. Patients are examined every 12 weeks for 1 year, and every 6 months for 4 years, then annually for 5 years.

ARM II (PEMBROLIZUMAB): Patients receive pembrolizumab intravenously (IV) over 30 minutes on days 1 and 22. Cycles repeat every 42 days for 52 weeks in the absence of disease progression or unacceptable toxicity.

All patients may undergo radiation therapy within 12 weeks of last breast cancer operation or after treatment. Patients may also undergo collection of blood samples throughout the trial.

After completion of study treatment, patients are followed up every 6 months for 5 years, then annually thereafter until 10 years from treatment randomization.

Being tested
Biospecimen Collection, Laboratory Biomarker Analysis, Patient Observation, Pembrolizumab, Quality-of-Life Assessment
Medical subject headings
Breast Carcinoma In Situ, Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood samples

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Patient ObservationOther

    Also called Active Surveillance, deferred therapy, expectant management, Observation

    Undergo standard monitoring

  • PembrolizumabBiological

    Also called BCD-201, GME 751, GME751, Keytruda

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo radiation therapy

Study groups in NCT02954874
Study groupRoleWhat they receive
Arm I (observation)ExperimentalPatients receive no treatment but are monitored at standard clinical intervals during first year after randomization. Patients are examined every 12 weeks for 1 year, every 6 months for 4 years, and then annually for 5 years. Patients may undergo radiation therapy within 12 weeks of last breast cancer operation or after treatment. Patients may also undergo collection of blood samples throughout the trial.
Receives: Procedure: Biospecimen Collection; Other: Laboratory Biomarker Analysis; Other: Patient Observation; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy
Arm II (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on days 1 and 22. Cycles repeat every 42 days for 52 weeks in the absence of disease progression or unacceptable toxicity. Patients may undergo radiation therapy within 12 weeks of last breast cancer operation or after treatment. Patients may also undergo collection of blood samples throughout the trial.
Receives: Procedure: Biospecimen Collection; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy

What is being measured

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

  1. Invasive disease-free survival (IDFS)

    The distributions of IDFS will be estimated using the Kaplan-Meier method, with 95% confidence intervals (CI) calculated using Greenwood's formula. Comparisons between the two treatment arms will be performed using the stratified log-rank test. The hazard ratios and 95% CIs will be based on the stratified Cox proportional hazard model with treatment as the only covariate. Secondary analyses of IDFS will be performed to describe consistency or divergence across subgroups. This will include a forest plot of treatment hazard ratios and associated 95% confidence intervals for each level of the stratification factors and major prognostic covariates (such as use of radiation therapy). The statistical significance of the interaction between treatment and each stratification factor or prognostic variable will be assessed.

    Measured: From date of randomization to date of first invasive recurrence, second invasive primary cancer (breast or not), or death due to any cause, assessed up to 10 years

  2. Severity of fatigue

    Measured by Patient Reported Outcomes Measurement Information System (PROMIS) fatigue scale. Will be compared between the two treatment groups by means of multiple linear regression with adjustment for the corresponding baseline measurement as well as whether or not the patient received radiation therapy which is known to be associated with post-treatment fatigue. No multiple comparisons adjustment will be employed since these outcomes evaluate the toxicity of the investigational drug. The clinical meaningfulness of each comparison will be considered.

    Measured: 55 weeks after randomization

  3. Physical function

    Reported by patients measured by PROMIS Global physical health scale. Will be compared between the two treatment groups by means of multiple linear regression with adjustment for the corresponding baseline measurement as well as whether or not the patient received radiation therapy which is known to be associated with post-treatment fatigue. No multiple comparisons adjustment will be employed since these outcomes evaluate the toxicity of the investigational drug. The clinical meaningfulness of each comparison will be considered.

    Measured: 55 weeks after randomization

Secondary outcomes (11)

  1. Overall survival (OS)

    The distributions of OS will be estimated using the Kaplan-Meier method, with 95% CI calculated using Greenwood's formula. Comparisons between the two treatment arms will be performed using the stratified log-rank test. The hazard ratios and 95% CIs will be based on the stratified Cox proportional hazard model with treatment as the only covariate.

    Measured: From date of randomization to date of death due to any cause, assessed up to 10 years

  2. Distant recurrence-free survival (DRFS)

    The distributions of DRFS will be estimated using the Kaplan-Meier method, with 95% CI calculated using Greenwood's formula. Comparisons between the two treatment arms will be performed using the stratified log-rank test. The hazard ratios and 95% CIs will be based on the stratified Cox proportional hazard model with treatment as the only covariate.

    Measured: From date of randomization to date of invasive distant disease recurrence, second invasive primary cancer (breast or not) or death due to any cause, assessed up to 10 years

  3. Incidence of adverse events

    Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Toxicity analysis will be conducted in all patients receiving at least one dose of MK-3475 (pembrolizumab). The incidence of adverse events will be reported.

    Measured: Up to 10 years

  4. Severity and frequency of treatment-related symptoms (diarrhea, nausea, rash, cough, and shortness of breath, musculoskeletal pain) over time of patients receiving pembrolizumab

    Compared without treatment. The distributions of the corresponding Patient Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) items will be compared between the two treatment groups using a mixed ordinal logistic regression model for repeated measures. The model will also include the corresponding baseline measurement and time. Presence of treatment-by-time interaction will be tested for each of these endpoints. Similar analyses will be performed for disease related symptoms. The descriptive and graphical methods suggested in Basch, et. al. will be used to summarize the distributions of different symptoms by treatment group over time.

    Measured: Up to 10 years

  5. Emotional function and disease-related symptoms in patients receiving pembrolizumab

    Assessed by PROMIS global mental health scale score. Will be compared between the two treatment groups using a mixed model for repeated measures analysis with adjustment for the baseline score and time. Presence of treatment-by-time interaction will be investigated.

    Measured: Up to 10 years

  6. Impact of treatment and treatment-related symptoms on physical function in patients without therapy

    Compared to patients receiving pembrolizumab. A multiple linear regression model will be performed with physical health scale score as an outcome and treatment and treatment related symptoms as covariates. Presence of treatment by each individual symptom item interactions will be investigated.

    Measured: 55 weeks after randomization

  7. Relationship between treatment-related symptoms and adherence to the study medication

    Will be investigated among patients randomized to pembrolizumab treatment group by means of multiple logistic regression. Patients who have been on study therapy for 70% or more of their expected time on therapy will be considered adherent.

    Measured: Up to 10 years

  8. Resolution of treatment-related symptoms in patients receiving pembrolizumab

    Compared to patients without treatment. A change in severity of the particular symptom will be compared between the two treatment groups by means of multiple linear regression with adjustment for the corresponding measurement at the 55 week assessment point.

    Measured: 18 months after randomization

  9. Long-term quality of life and symptoms between the two treatment groups

    Mixed models for repeated measures analysis will be used with adjustment for scores at 18 months to examine changes in physical and emotional domain scores, fatigue and other persistent symptoms over the course

    Measured: Up to 60 months after randomization

  10. Role of pro-inflammatory cytokines in the development of pembrolizumab associated symptoms

    Specifically focused on treatment-associated fatigue. This will be compared to patients in the observation group.

    Measured: Up to 55 weeks

  11. Single nucleotide polymorphisms (SNPs) in the promotor region of pro-inflammatory cytokine genes and the risk for development and severity of treatment-associated fatigue and other symptoms

    The role of these SNPs in the persistence of long-term fatigue in all patients will also be explored using treatment assignment as a covariate.

    Measured: Up to 10 years

Timeline

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

  1. First posted4 Nov 2016 (estimated)
  2. Study start18 Jan 2017
  3. Primary completion3 Aug 2026
  4. Study completion27 Aug 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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,195 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02954874
Sponsor's protocol ID
NCI-2016-01595
Other IDs
NCI-2016-01595, S1418/BR006, s16-02231, S1418, S1418, U10CA180888
Status last verified
Aug 2026
First submitted
3 Nov 2016
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Biospecimen Collection, Laboratory Biomarker Analysis and Patient Observation in people with Breast Carcinoma In Situ and Invasive Breast Carcinoma, run by National Cancer Institute (NCI) at 919 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 47 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 919 sites in United States, Canada, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Invasive disease-free survival (IDFS) (time frame: From date of randomization to date of first invasive recurrence, second invasive primary cancer (breast or not), or death due to any cause, assessed up to 10 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02954874.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

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