A Study Evaluating Trastuzumab Emtansine Plus Pertuzumab Compared With Chemotherapy Plus Trastuzumab and Pertuzumab for Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

NCT ID: NCT02131064

Last Updated: 2019-07-02

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

444 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-25

Study Completion Date

2018-05-29

Brief Summary

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This is a randomized, multicenter, open-label, two-arm study in treatment-naive participants with operable, locally advanced, or inflammatory, centrally-assessed HER2-positive early breast cancer (EBC) whose primary tumors were greater than or equal to (\>/=) 2 centimeters (cm). The study was designed to evaluate the efficacy and safety of trastuzumab emtansine + pertuzumab (experimental arm; T-DM1 + P) versus chemotherapy, trastuzumab + pertuzumab (control arm; TCH + P). The study comprised a neoadjuvant treatment period, followed by surgery, and an adjuvant treatment period.

Treatment can be stopped due to disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination.

Detailed Description

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Conditions

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Breast Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Trastuzumab (TCH) + Pertuzumab

Participants will receive pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion followed by trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion followed by docetaxel 75 milligrams per square meter (mg/m\^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter\* minute (mg/mL\*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).

Group Type ACTIVE_COMPARATOR

Carboplatin

Intervention Type DRUG

Carboplatin IV infusion at a dose to achieve an AUC of 6 mg\*min/mL q3w

Docetaxel

Intervention Type DRUG

Docetaxel 75 mg/m\^2 IV infusion q3w

Pertuzumab

Intervention Type DRUG

Pertuzumab 840 mg (loading dose); and 420 mg (maintenance dose) IV infusion q3w

Trastuzumab

Intervention Type DRUG

Trastuzumab 8 mg/kg (loading dose); and 6 mg/kg (maintenance dose) IV infusion q3w

Trastuzumab Emtansine (T-DM1) + Pertuzumab

Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).

Group Type EXPERIMENTAL

Pertuzumab

Intervention Type DRUG

Pertuzumab 840 mg (loading dose); and 420 mg (maintenance dose) IV infusion q3w

Trastuzumab Emtansine

Intervention Type DRUG

Trastuzumab Emtansine 3.6 mg/kg IV infusion q3w

Interventions

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Carboplatin

Carboplatin IV infusion at a dose to achieve an AUC of 6 mg\*min/mL q3w

Intervention Type DRUG

Docetaxel

Docetaxel 75 mg/m\^2 IV infusion q3w

Intervention Type DRUG

Pertuzumab

Pertuzumab 840 mg (loading dose); and 420 mg (maintenance dose) IV infusion q3w

Intervention Type DRUG

Trastuzumab

Trastuzumab 8 mg/kg (loading dose); and 6 mg/kg (maintenance dose) IV infusion q3w

Intervention Type DRUG

Trastuzumab Emtansine

Trastuzumab Emtansine 3.6 mg/kg IV infusion q3w

Intervention Type DRUG

Other Intervention Names

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Perjeta®, RO4368451 Herceptin® Kadcyla®, RO5304020

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed invasive breast cancer with a primary tumor size of greater than (\>) 2 cm
* HER2-positive breast cancer
* Participants with multifocal tumors (more than one tumor confined to the same quadrant as the primary tumor) are eligible provided all discrete lesions are sampled and centrally confirmed as HER2 positive
* Stage at presentation: cT2-cT4, cN0-cN3, cM0, according to American Joint Committee on Cancer (AJCC) staging system
* Known hormone receptor status of the primary tumor
* Participant agreement to undergo mastectomy or breast-conserving surgery after neoadjuvant therapy
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Baseline Left Ventricular Ejection Fraction (LVEF) \>/= 55 percent (%) measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA)
* Effective contraception as defined by protocol

Exclusion Criteria

* Stage IV (metastatic) breast cancer
* Participants who have received prior anti-cancer therapy for breast cancer except those participants with a history of breast lobular carcinoma in situ (LCIS) that was surgically managed or ductal carcinoma in situ (DCIS) treated exclusively with mastectomy. In case of prior history of LCIS/DCIS, \>5 years must have passed from surgery until diagnosis of current breast cancer
* Participants with multicentric (multiple tumors involving more than 1 quadrant) or bilateral breast cancer
* Participants who have undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
* Axillary lymph node dissection or positive sentinel lymph node prior to start of neoadjuvant therapy
* History of concurrent or previously non-breast malignancies except for appropriately treated (1) non-melanoma skin cancer and (2) in situ carcinomas, including cervix, colon, and skin. A participant with previous invasive non-breast cancer is eligible provided he/she has been disease-free \>/= 5 years
* Treatment with any investigational drug within 28 days prior to randomization
* Current National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0
* Any significant concurrent medical or surgical conditions or findings that would jeopardize the participant's safety or ability to complete the study
* Current pregnancy or breastfeeding
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr

Fullerton, California, United States

Site Status

Cancer Care Assoc Med Group

Los Angeles, California, United States

Site Status

Coastal Integrative Cancer Care

San Luis Obispo, California, United States

Site Status

Central Coast Medical Oncology

Santa Maria, California, United States

Site Status

UCLA Hematology/Oncology

Santa Monica, California, United States

Site Status

Memorial Cancer Institute

Hollywood, Florida, United States

Site Status

Md Anderson Cancer Center Orlando

Orlando, Florida, United States

Site Status

New England Cancer Specialists

Scarborough, Maine, United States

Site Status

Comprehensive Cancer Centers of Nevada - Henderson

Henderson, Nevada, United States

Site Status

ProHEALTH Care Associates LLP

Lake Success, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Hope A Women's Cancer Center

Asheville, North Carolina, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Roper Bon Secours St. Francis Cancer Center

Charleston, South Carolina, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

UZ Antwerpen

Edegem, , Belgium

Site Status

UZ Leuven Gasthuisberg

Leuven, , Belgium

Site Status

Clinique Saint-Joseph

Liège, , Belgium

Site Status

Clinique Ste-Elisabeth, Pharmacie

Namur, , Belgium

Site Status

Sint Augustinus Wilrijk

Wilrijk, , Belgium

Site Status

Cross Cancer Institute ; Dept of Medical Oncology

Edmonton, Alberta, Canada

Site Status

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status

St. Michael'S Hospital

Toronto, Ontario, Canada

Site Status

Chum Hospital Notre Dame

Montreal, Quebec, Canada

Site Status

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, Canada

Site Status

CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY

Québec, , Canada

Site Status

Ico - Paul Papin

Angers, , France

Site Status

HOPITAL JEAN MINJOZ; Oncologie

Besançon, , France

Site Status

Hopital Morvan

Brest, , France

Site Status

CHD Les Oudairies

La Roche-sur-Yon, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Institut Paoli Calmettes

Marseille, , France

Site Status

Centre Catherine De Sienne

Nantes, , France

Site Status

Centre Rene Gauducheau

Saint-Herblain, , France

Site Status

Nouvel Hopital Civil - CHU Strasbourg

Strasbourg, , France

Site Status

Klinikum Sindelfingen-Böblingen; Frauenklinik

Böblingen, , Germany

Site Status

Luisenkrankenhaus GmbH, Brustzentrum

Düsseldorf, , Germany

Site Status

Universitätsklinikum Erlangen; Frauenklinik

Erlangen, , Germany

Site Status

Universitätsklinikum Mainz

Mainz, , Germany

Site Status

Interdisziplinäres Onkologisches Zentrum

München, , Germany

Site Status

Moscow City Oncology Hospital #62

Moscovskaya Oblast, Moscow Oblast, Russia

Site Status

Regional Oncology Hospital Of Kursk; Chemotherapy

Kislino, Kursk Region, , Russia

Site Status

S.I. Russian Oncological Research Center n.a. N.N. Blokhin

Moscow, , Russia

Site Status

State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis

Orenburg, , Russia

Site Status

Saint-Petersburg City Clinical Oncology Dispensary

Saint Petersburg, , Russia

Site Status

Railway Clinical Hospital on Saratov - 2 Station Oao "Rzhd"

Saratov, , Russia

Site Status

National Cancer Center

Gyeonggi-do, , South Korea

Site Status

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital

Seoul, , South Korea

Site Status

Asan Medical Center - Oncology

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, Spain

Site Status

IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia

Donostia / San Sebastian, Guipuzcoa, Spain

Site Status

Hospital Universitari de Lleida Arnau de Vilanova

Lleida, Lerida, Spain

Site Status

Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología

A Coruña, , Spain

Site Status

Hospital Nuestra Señora de Sonsoles; servicio de Oncologia

Ávila, , Spain

Site Status

Hospital del Mar; Servicio de Oncologia

Barcelona, , Spain

Site Status

Fundacio Santa Creu I Sant Pau

Barcelona, , Spain

Site Status

Complejo Hospitalario de Jaen

Jaén, , Spain

Site Status

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario Clínico San Carlos; Servicio de Oncologia

Madrid, , Spain

Site Status

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, , Spain

Site Status

Hospital Quiron de Madrid; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, , Spain

Site Status

Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery

Kaohsiung City, , Taiwan

Site Status

National Taiwan Uni Hospital

Taipei, , Taiwan

Site Status

Mackay Memorial Hospital; Dept of Surgery

Taipei, , Taiwan

Site Status

Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Tri-Service General Hospital

Taipei, , Taiwan

Site Status

Cherkassy Regional Oncological Hospital

Cherkassy, , Ukraine

Site Status

State Medical Academy; Oncology

Dnipropetrovsk, , Ukraine

Site Status

Karkiv Regional Oncology Center

Kharkiv, , Ukraine

Site Status

Lvov State Regional Center

Lviv, , Ukraine

Site Status

Countries

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United States Belgium Canada France Germany Russia South Korea Spain Taiwan Ukraine

References

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de Haas SL, Slamon DJ, Martin M, Press MF, Lewis GD, Lambertini C, Prat A, Lopez-Valverde V, Boulet T, Hurvitz SA. Tumor biomarkers and efficacy in patients treated with trastuzumab emtansine + pertuzumab versus standard of care in HER2-positive early breast cancer: an open-label, phase III study (KRISTINE). Breast Cancer Res. 2023 Jan 11;25(1):2. doi: 10.1186/s13058-022-01587-z.

Reference Type DERIVED
PMID: 36631725 (View on PubMed)

Hurvitz SA, Martin M, Jung KH, Huang CS, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Fasching PA, Afenjar K, Spera G, Lopez-Valverde V, Song C, Trask P, Boulet T, Sparano JA, Symmans WF, Thompson AM, Slamon D. Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study. J Clin Oncol. 2019 Sep 1;37(25):2206-2216. doi: 10.1200/JCO.19.00882. Epub 2019 Jun 3.

Reference Type DERIVED
PMID: 31157583 (View on PubMed)

Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang CS, Thompson AM, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Beckmann MW, Afenjar K, Fresco R, Helms HJ, Xu J, Lin YG, Sparano J, Slamon D. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):115-126. doi: 10.1016/S1470-2045(17)30716-7. Epub 2017 Nov 23.

Reference Type DERIVED
PMID: 29175149 (View on PubMed)

Other Identifiers

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TRIO021

Identifier Type: OTHER

Identifier Source: secondary_id

2012-004879-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO28408

Identifier Type: -

Identifier Source: org_study_id

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