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T-DM1 and Tucatinib Compared with T-DM1 Alone in Preventing Relapses in People with High Risk HER2-Positive Breast Cancer, the CompassHER2 RD Trial

Trial Status: Active

This phase III trial compares the effect of usual treatment with trastuzumab emtansine (T-DM1) alone vs. T-DM1 in combination with tucatinib. T-DM1 is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called DM1. Trastuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors, and delivers DM1 to kill them. Tucatinib blocks HER2, which may help keep cancer cells from growing and may kill them. Giving T-DM1 in combination with tucatinib may work better in preventing breast cancer from relapsing in patients with HER2 positive breast cancer compared to T-DM1 alone.

Inclusion Criteria

  • HER2-positive status will be based on pretreatment biopsy material and defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) according to current American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines. Central testing is not required * Known hormone receptor (HR) status as defined by ASCO/CAP guidelines. Hormone receptor positive status can be determined by either known positive estrogen receptor (ER) or known positive progesterone receptor (PR) status; hormone receptor negative status must be determined by both known negative ER and known negative PR
  • Patients with clinical stage T1-4, N0-3 disease at presentation and residual invasive disease postoperatively as defined above are eligible. (Note: Patients with T1a/bN0 tumors are not eligible)
  • Patients with residual HR-negative, HER2 positive (+) disease in the breast and/or lymph nodes per the surgical pathology report are eligible; however, patients with HR+ HER2+ cancers must have node-positive residual disease per the surgical pathology report in order to qualify for the study. The presence of residual invasive disease in the breast is not mandatory for these patients. Note: The presence of micrometastases in lymph nodes after preoperative therapy counts as residual disease, whereas the presence of isolated tumor cells does not
  • Patients with synchronous bilateral invasive disease are eligible provided both lesions were confirmed to be HER2-positive, and at least one of the lesions meets the criteria outlined above. Multifocal disease is allowed, as long as the largest biopsied breast tumor was HER2-positive
  • Patients must have received neoadjuvant chemotherapy with one of the following regimens: docetaxel/trastuzumab/pertuzumab (THP), paclitaxel/methotrexate/cisplatin (TMP), doxorubicin/cyclophosphamide/paclitaxel/trastuzumab/pertuzumab (AC-TH(P)); docetaxel/carboplatin/trastuzumab/pertuzumab (TCH(P)); fluorouracil/doxorubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab (FAC-TH(P)), or fluorouracil/epirubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab (FEC-TH(P)). Note: apart from TCHP, where T is docetaxel, treatment with docetaxel or paclitaxel is acceptable
  • Prior receipt of T-DM1 in the neoadjuvant setting is not allowed. * Prior treatment must have consisted of >= 6 cycles of chemotherapy and HER2-directed therapy, with a total duration of >= 12 weeks, including at least 9 weeks of preoperative taxane and trastuzumab with or without pertuzumab (or Food and Drug Administration [FDA]-approved biosimilars). Patients who have received at least 9 weeks of preoperative taxane, pertuzumab and margetuximab are also eligible if they received >= 6 cycles of systemic therapy prior to enrollment. Note: Patients who complete at least nine of a planned twelve doses of weekly paclitaxel, or three of a planned four doses of docetaxel, but discontinue prematurely due to toxicity (i.e. peripheral neuropathy =< grade 1) are eligible. Patients receiving dose-dense chemotherapy regimens are also eligible. Prior use of nab-paclitaxel (Abraxane) instead of paclitaxel or docetaxel is permitted. Prior use of subcutaneous trastuzumab (Hylecta) and subcutaneous trastuzumab and pertuzumab (Phesgo) is also allowed. * Patients who received neoadjuvant systemic therapy which included experimental HER2-targeted therapy/therapies are potentially eligible, as long as the investigational agent was not a HER2-targeted antibody-drug conjugate (e.g. T-DM1, DS-8201a [trastuzumab deruxtecan]) or a HER2 targeted tyrosine kinase inhibitor (TKI) (e.g. tucatinib, lapatinib, neratinib).
  • Patients may have received =< 1 cycles of T-DM1 in the adjuvant setting. Note: These patients will be randomized to receive a further 14 cycles of T-DM1 and tucatinib/placebo as tolerated. The most recent cycle of T-DM1 should have been administered =< 5 weeks prior to registration * N.B: Both of the following two criteria need to be met for the patient to be eligible for this study ** An interval of no more than 12 weeks between the completion date of the last definitive treatment (e.g. postoperative chemotherapy or radiation, or if neither given, breast surgical date) and the date of registration ** Patients must be registered on study within =< 180 days of the date of the most recent definitive breast cancer surgery (not including reconstructive surgery)
  • All systemic chemotherapy should have been completed preoperatively unless participating in EA1181 (CompassHER2 pathologic complete response [pCR]) or the BIG DECRESCENDO Trial (which is very similar to CompassHER2 pCR in terms of study design, drugs, and eligibility). Patients who participated in EA1181 or MA41 and proceeded to surgery immediately after the de-escalated trial regimen must receive postoperative chemotherapy to complete a total of >= 6 cycles of systemic treatment prior to enrollment on A011801, as outlined above (e.g. 4 cycles pre-operatively, and 2 cycles post-operatively)
  • Toxicities related to prior systemic treatment should have resolved or be at baseline, apart from alopecia and peripheral neuropathy =< grade 1
  • Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes as follows: * Breast surgery: total mastectomy with no gross residual disease at the margin of resection, or breast-conserving surgery with histologically negative margins of excision * For patients who undergo breast-conserving surgery, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. Patients with margins positive for classic lobular carcinoma in situ (LCIS) are eligible without additional resection * Lymph node surgery ** The axilla needs to be evaluated with either sentinel node biopsy or axillary lymph node dissection. If patients have a sentinel lymph node biopsy and sentinel nodes are negative, no further axillary treatment is necessary. If patients have isolated tumor cells (ITCs) in the setting of residual breast disease, at least one of the following is required: axillary lymph node dissection (ALND) or planned nodal irradiation. If patients have micro- or macro-metastatic nodal disease, an ALND is required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Hemoglobin >= 8 g/dL (Note: packed red blood cells [PRBC] transfusion is not permitted to achieve eligibility)
  • Platelet count >= 100,000/mm^3
  • Creatinine =< 1.5 x upper limit of normal (ULN)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) or direct bilirubin within the institutional normal range for patients with Gilbert’s syndrome
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Screening left ventricular ejection fraction (LVEF) >= 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no decrease in LVEF by more than 15% absolute points from the pre-chemotherapy LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >= 55% after completion of neoadjuvant chemotherapy. Note: LVEF assessment may be repeated once up to 3 weeks following the initial screening assessment to assess eligibility

Exclusion Criteria

  • No adjuvant treatment with any anti-cancer investigational drug within 28 days prior to registration
  • Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative serum pregnancy test done =< 7 days prior to registration is required
  • Patients with known active and/or untreated hepatitis B or hepatitis C or chronic liver disease are ineligible. Patients with a diagnosis of hepatitis B or C that has been treated and cleared and normal liver function are eligible to participate in the study if the other eligibility parameters are met
  • Stage IV (metastatic) breast cancer
  • History of any prior (ipsi- or contralateral) invasive breast cancer within 3 years of registration
  • Patients with ER+ HER2+ residual invasive disease that is lymph node-negative per the surgical pathology report
  • Evidence of recurrent disease following preoperative therapy and surgery
  • Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation)
  • History of exposure to the following cumulative doses of anthracyclines: doxorubicin > 240 mg/m^2; epirubicin or liposomal doxorubicin-hydrochloride (Myocet) > 480 mg/m^2. For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m^2
  • Cardiopulmonary dysfunction as defined by any of the following: * History of National Cancer Institute (NCI) CTCAE version (v) 5.0 grade >= 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria class >= II * Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease * High-risk uncontrolled arrhythmias: i.e., atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade atrioventricular block (AV)-block (second degree AV-block type 2 [Mobitz 2] or third degree AV-block) * Significant symptoms (grade >= 2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia while or since receiving preoperative therapy * History of a decrease in left ventricular ejection fraction (LVEF) to < 40% with prior trastuzumab treatment (e.g., during preoperative therapy) * Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg)
  • Current severe, uncontrolled systemic disease
  • Major surgical procedure unrelated to breast cancer or significant traumatic injury within 28 days prior to registration or anticipation of the need for major surgery during the course of study treatment
  • History of intolerance, including grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product
  • Peripheral neuropathy of any etiology that exceeds grade 1
  • Assessment by the investigator as being unable or unwilling to comply with the requirements of the protocol
  • Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to registration is prohibited. * Please note that use of sensitive CYP3A substrates should be avoided two weeks before registration and during study treatment. Additionally, CYP3A4 or CYP2C8 inducers are prohibited as concomitant medications within 5 days following discontinuation of tucatinib treatment. Patients who require medications that are known to be sensitive substrates of CYP3A4 with a narrow therapeutic window should be excluded.

Arizona

Kingman
Kingman Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 773-702-9171
Phoenix
Cancer Center at Saint Joseph's
Status: ACTIVE
Contact: Site Public Contact
Phone: 602-406-8222

Arkansas

Ft. Smith
Mercy Hospital Fort Smith
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-378-9373
Hot Springs
CHI Saint Vincent Cancer Center Hot Springs
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

California

Arroyo Grande
Mission Hope Medical Oncology - Arroyo Grande
Status: ACTIVE
Contact: Site Public Contact
Phone: 916-851-2283
PCR Oncology
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
San Luis Obispo
Pacific Central Coast Health Center-San Luis Obispo
Status: ACTIVE
Contact: Site Public Contact
Santa Maria
Mission Hope Medical Oncology - Santa Maria
Status: ACTIVE
Contact: Site Public Contact
Phone: 916-851-2283

Colorado

Colorado Springs
Penrose-Saint Francis Healthcare
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Rocky Mountain Cancer Centers-Penrose
Status: ACTIVE
Contact: Site Public Contact
Phone: 303-777-2663
Denver
Porter Adventist Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Durango
Mercy Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Southwest Oncology PC
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Lakewood
Saint Anthony Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Littleton
Littleton Adventist Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Longmont
Longmont United Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Rocky Mountain Cancer Centers-Longmont
Status: ACTIVE
Contact: Site Public Contact
Phone: 303-777-2663
Parker
Parker Adventist Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Pueblo
Saint Mary Corwin Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Florida

Pensacola
Sacred Heart Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 850-416-4611

Illinois

Mount Vernon
Good Samaritan Regional Health Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 618-242-4600

Iowa

Ames
Mary Greeley Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-956-4132
McFarland Clinic PC - Ames
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-239-4734
Boone
McFarland Clinic PC-Boone
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-956-4132
Clive
Medical Oncology and Hematology Associates-West Des Moines
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Mercy Cancer Center-West Lakes
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Council Bluffs
Alegent Health Mercy Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Creston
Greater Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Des Moines
Medical Oncology and Hematology Associates-Laurel
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Mercy Medical Center - Des Moines
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Fort Dodge
McFarland Clinic PC-Trinity Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-956-4132
Jefferson
McFarland Clinic PC-Jefferson
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-956-4132
Marshalltown
McFarland Clinic PC-Marshalltown
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-956-4132
West Des Moines
Mercy Medical Center-West Lakes
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Kentucky

Bardstown
Flaget Memorial Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Corbin
Commonwealth Cancer Center-Corbin
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Lexington
Saint Joseph Hospital East
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Saint Joseph Radiation Oncology Resource Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
London
Saint Joseph London
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Louisville
Jewish Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Jewish Hospital Medical Center Northeast
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Saints Mary and Elizabeth Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Shepherdsville
Jewish Hospital Medical Center South
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Michigan

Adrian
Hickman Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 517-265-0116
Monroe
Toledo Clinic Cancer Centers-Monroe
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-444-3561

Mississippi

Jackson
University of Mississippi Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 601-815-6700

Missouri

Ballwin
Saint Louis Cancer and Breast Institute-Ballwin
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-251-7058
Joplin
Freeman Health System
Status: ACTIVE
Contact: Site Public Contact
Phone: 417-347-4030
Mercy Hospital Joplin
Status: ACTIVE
Contact: Site Public Contact
Phone: 417-556-3074
Rolla
Delbert Day Cancer Institute at PCRMC
Status: ACTIVE
Contact: Site Public Contact
Phone: 573-458-8776
Mercy Clinic-Rolla-Cancer and Hematology
Status: ACTIVE
Contact: Site Public Contact
Phone: 573-458-6379
Saint Joseph
Heartland Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 816-271-7937
Saint Louis
Mercy Hospital Saint Louis
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-251-7066
Mercy Hospital South
Status: ACTIVE
Contact: Site Public Contact
Saint Louis Cancer and Breast Institute-South City
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-353-1870
Springfield
CoxHealth South Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 417-269-4520
Mercy Hospital Springfield
Status: ACTIVE
Contact: Site Public Contact
Phone: 417-269-4520
Washington
Mercy Hospital Washington
Status: ACTIVE
Contact: Site Public Contact
Phone: 636-390-1600

Nebraska

Grand Island
CHI Health Saint Francis
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Kearney
CHI Health Good Samaritan
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Lincoln
Saint Elizabeth Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Omaha
Alegent Health Bergan Mercy Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Alegent Health Immanuel Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Alegent Health Lakeside Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Creighton University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Papillion
Midlands Community Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Nevada

Carson City
Carson Tahoe Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Henderson
21st Century Oncology-Henderson
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Cancer and Blood Specialists-Henderson
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada - Henderson
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada-Horizon Ridge
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada-Southeast Henderson
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Las Vegas Cancer Center-Henderson
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Las Vegas Urology - Green Valley
Status: ACTIVE
Contact: Site Public Contact
Las Vegas Urology - Pebble
Status: ACTIVE
Contact: Site Public Contact
OptumCare Cancer Care at Seven Hills
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Urology Specialists of Nevada - Green Valley
Status: ACTIVE
Contact: Site Public Contact
Las Vegas
21st Century Oncology
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
21st Century Oncology-Fort Apache
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
21st Century Oncology-Vegas Tenaya
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Alliance for Childhood Diseases / Cure 4 the Kids Foundation
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada - Central Valley
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada - Northwest
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada - Town Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Comprehensive Cancer Centers of Nevada-Summerlin
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Desert West Surgery
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Hope Cancer Care of Nevada
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Las Vegas Cancer Center-Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Las Vegas Prostate Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Las Vegas Urology - Cathedral Rock
Status: ACTIVE
Contact: Site Public Contact
Las Vegas Urology - Pecos
Status: ACTIVE
Contact: Site Public Contact
Las Vegas Urology - Smoke Ranch
Status: ACTIVE
Contact: Site Public Contact
Las Vegas Urology - Sunset
Status: ACTIVE
Contact: Site Public Contact
OptumCare Cancer Care at Fort Apache
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
OptumCare Cancer Care at MountainView
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
OptumCare Cancer Care at Oakey
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Summerlin Hospital Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Sunrise Hospital and Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
University Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
University Medical Center of Southern Nevada
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Urology Specialists of Nevada - Central
Status: ACTIVE
Contact: Site Public Contact
Urology Specialists of Nevada - Northwest
Status: ACTIVE
Contact: Site Public Contact
Urology Specialists of Nevada - Southwest
Status: ACTIVE
Contact: Site Public Contact
Pahrump
Hope Cancer Care of Nevada-Pahrump
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Reno
Radiation Oncology Associates
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Renown Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013
Saint Mary's Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 702-384-0013

New Hampshire

Concord
New Hampshire Oncology Hematology PA-Concord
Status: ACTIVE
Contact: Site Public Contact
Phone: 603-224-2556
Manchester
Solinsky Center for Cancer Care
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-339-6484

New Jersey

Englewood
Englewood Hospital and Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 201-894-3456

New York

Auburn
Hematology Oncology Associates of Central New York-Auburn
Status: ACTIVE
Contact: Site Public Contact
Phone: 315-472-7504
East Syracuse
Hematology Oncology Associates of Central New York-East Syracuse
Status: ACTIVE
Contact: Site Public Contact
Phone: 315-472-7504
Syracuse
Hematology Oncology Associates of Central New York-Onondaga Hill
Status: ACTIVE
Contact: Site Public Contact
Phone: 315-472-7504

Ohio

Alliance
Aultman Alliance Community Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 330-363-1250
Canton
Aultman Health Foundation
Status: ACTIVE
Contact: Site Public Contact
Phone: 330-363-7274
Cincinnati
Bethesda North Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Good Samaritan Hospital - Cincinnati
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
TriHealth Cancer Institute-Anderson
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
TriHealth Cancer Institute-Westside
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Toledo
Mercy Health - Saint Anne Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 614-488-2118
Toledo Clinic Cancer Centers-Toledo
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-444-3561

Oklahoma

Oklahoma City
Mercy Hospital Oklahoma City
Status: ACTIVE
Contact: Site Public Contact
Phone: 405-752-3402

Pennsylvania

Pottstown
Pottstown Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 610-327-7544
West Reading
Reading Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 610-988-9323

Rhode Island

Providence
Women and Infants Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 401-274-1122

South Carolina

Greenville
Saint Francis Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 864-603-6213
Saint Francis Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 864-603-6213
West Columbia
Lexington Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 803-791-2105

Texas

Bryan
Saint Joseph Regional Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Houston
Houston Methodist Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 713-790-2700
Laredo
Doctor's Hospital of Laredo
Status: ACTIVE
Contact: Site Public Contact
Phone: 956-523-2650

Virginia

Mechanicsville
Bon Secours Memorial Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 804-893-8663
Midlothian
Bon Secours Saint Francis Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 804-893-8663
Norfolk
Bon Secours DePaul Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 804-893-8663
Portsmouth
Bon Secours Maryview Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 804-893-8663
Richmond
Bon Secours Cancer Institute at Reynolds Crossing
Status: ACTIVE
Contact: Site Public Contact
Phone: 804-893-8663
Bon Secours Saint Mary's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 804-893-8663
Suffolk
Bon Secours Health Center at Harbour View
Status: ACTIVE
Contact: Site Public Contact
Phone: 804-893-8663

Washington

Bellevue
Overlake Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 425-688-5407
Bremerton
Harrison HealthPartners Hematology and Oncology-Bremerton
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Harrison Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Burien
Highline Medical Center-Main Campus
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Enumclaw
Saint Elizabeth Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Federal Way
Saint Francis Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Lakewood
Saint Clare Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Poulsbo
Harrison HealthPartners Hematology and Oncology-Poulsbo
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Renton
Valley Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 425-228-3440
Tacoma
Franciscan Research Center-Northwest Medical Plaza
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Northwest Medical Specialties PLLC
Status: ACTIVE
Contact: Site Public Contact
Phone: 253-306-0532

PRIMARY OBJECTIVE:

I. To determine if the invasive disease-free survival (iDFS) with T-DM1 and tucatinib is superior to the iDFS in the control arm (T-DM1 + placebo) when administered to high risk patients with HER2-positive breast cancer and residual disease after neoadjuvant HER2-directed therapy.

SECONDARY OBJECTIVES:

I. To evaluate whether treatment with tucatinib plus T-DM1 compared to treatment with T-DM1 alone (T-DM1 plus placebo) improves the following:

Ia. Overall survival (OS).

Ib. Breast cancer free survival (BCFS).

Ic. Distant recurrence-free survival (DRFS).

Id. Disease-free survival (DFS).

Ie. Brain metastases-free survival (BMFS).

II. To evaluate whether treatment with tucatinib plus T-DM1 compared to treatment with T-DM1 alone (T-DM1 plus placebo) reduces the incidence of brain metastases.

SECONDARY CORRELATIVE OBJECTIVES:

I. To evaluate the association of tumor infiltrating lymphocyte (TIL) levels in both the primary tumor and the residual disease specimen with iDFS.

II. To determine whether there is evidence of differential treatment benefit of T-DM1 and tucatinib compared to T-DM1 and placebo in high TIL cancers compared to low TIL cancers (assessed in both the pre-neoadjuvant tumor tissue and the residual cancer tissue).

III. To evaluate the association between iDFS and the presence of detectable circulating tumor cells (CTC) at baseline, at completion of study therapy and/or 1 year after completion of study therapy.

IV. To determine the difference in absolute magnitude of benefit of tucatinib (in terms of iDFS) in the subgroup of patients with detectable CTC at baseline and the subgroup of patients without detectable CTC at baseline.

LOCAL REGIONAL EXPLORATORY OBJECTIVES:

I. To determine local regional recurrence following breast conservation based on margin width (no ink on tumor, close, > 2 mm).

II. To determine local regional recurrence following breast conservation with or without boost.

PATIENT-REPORTED OUTCOMES:

I. To compare quality of life (QOL) after approximately 8 cycles of the study as assessed by the Functional Assessment of Cancer Therapy (FACT)-Breast Cancer (B) Trial Outcome Index between patients randomized to T-DM1 + tucatinib or T-DM1 + placebo. (Primary Objective)

II. To compare QOL after approximately 13 cycles of the study as assessed by the FACT-B Trial Outcome Index between patients randomized to T-DM1 + tucatinib or T-DM1 + placebo. (Secondary Objective)

III. To compare various QOL domains after approximately 8 and 13 cycles of the study as assessed by the 5 subscales of the FACT-B questionnaire between patients randomized to T-DM1 + tucatinib or T-DM1 + placebo. (Exploratory Objective)

IV. To compare self-reported patient adherence and reasons for non-adherence after 1, 4, 8, and 13 cycles of the study as assessed by the Voils instrument (Domains of Subjective Extent of Nonadherence [DOSE-Nonadherence]) between patients randomized to T-DM1 + tucatinib or T-DM1 + placebo. (Exploratory Objective)

V. To compare self-reported symptomatic adverse events after 1, 4, 8, and 13 cycles of the study assessed by the Patient-Reported Outcomes (PRO) - Common Terminology Criteria for Adverse Events (CTCAE) between patients randomized to T-DM1 + tucatinib or T-DM1 + placebo. (Exploratory Objective)

TO-BE-DETERMINED CORRELATIVE OBJECTIVES:

I. To evaluate the association of circulating tumor deoxyribonucleic acid (ctDNA) tumor-specific mutations (at baseline and after completion of adjuvant HER2-directed therapy) with iDFS.

II. To evaluate the association of breast cancer intrinsic subtype and other transcriptional signatures in both the primary tumor and the residual disease specimen with iDFS.

PHARMACOKINETIC OBJECTIVES:

I. To characterize the pharmacokinetic (PK) of T-DM1 in all patients.

II. To characterize the PK of tucatinib in tucatinib-treated patients.

III. To investigate exposure–effect (efficacy and safety) relationships in tucatinib-treated patients.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive T-DM1 intravenously (IV) over 30-90 minutes on day 1 and placebo orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive T-DM1 IV over 30-90 minutes on day 1 and tucatinib PO BID on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 6 months for 10 years.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Alliance for Clinical Trials in Oncology

Principal Investigator
Ciara C. O'Sullivan

  • Primary ID A011801
  • Secondary IDs NCI-2020-03770
  • Clinicaltrials.gov ID NCT04457596