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

NCT02131064 | Completed Phase 3 Results

• 3 other identifiers: BO28408TRIO0212012-004879-38
• Study Type: interventional
• Target: 444
• Locations: 10 countries
• Sites: 79

Brief Summary

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.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples

  tpCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( that is \[i.e.\], ypT0/is, ypN0 in the American Joint Committee on Cancer \[AJCC\] staging system, 7th edition). Percentage of participants with tpCR was reported.

  Pre-surgery (within 6 weeks after neoadjuvant therapy; up to approximately 6 months)

Secondary Outcomes (21)

• Overall Survival

  From randomization until death (up to approximately 47 months)

• Percentage of Participants Who Received Breast-Conserving Surgery (BCS)

  Surgery performed after completion of neoadjuvant therapy (approximately 6 months after neoadjuvant period)

• Event-Free Survival

  From randomization up to disease progression or recurrence or death (up to approximately 47 months)

• Invasive Disease-free Survival (IDFS)

  From surgery to the first documented occurrence of IDFC event (up to approximately 47 months)

• Percentage of Participants by Response for Neuropathy Single Item

  Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months)

Study Arms (2)

Trastuzumab (TCH) + Pertuzumab

ACTIVE COMPARATOR

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).

Drug: Carboplatin; Drug: Docetaxel; Drug: Pertuzumab; Drug: Trastuzumab

Trastuzumab Emtansine (T-DM1) + Pertuzumab

EXPERIMENTAL

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).

Drug: Pertuzumab; Drug: Trastuzumab Emtansine

Interventions

Carboplatin DRUG

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

Trastuzumab (TCH) + Pertuzumab

Docetaxel DRUG

Docetaxel 75 mg/m\^2 IV infusion q3w

Trastuzumab (TCH) + Pertuzumab

Pertuzumab DRUG

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

Also known as: Perjeta®, RO4368451

Trastuzumab (TCH) + Pertuzumab; Trastuzumab Emtansine (T-DM1) + Pertuzumab

Trastuzumab DRUG

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

Also known as: Herceptin®

Trastuzumab (TCH) + Pertuzumab

Trastuzumab Emtansine DRUG

Trastuzumab Emtansine 3.6 mg/kg IV infusion q3w

Also known as: Kadcyla®, RO5304020

Trastuzumab Emtansine (T-DM1) + Pertuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (79)

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

Fullerton, California, 92835, United States

Location

Cancer Care Assoc Med Group

Los Angeles, California, 90095-1772, United States

Location

Coastal Integrative Cancer Care

San Luis Obispo, California, 93401, United States

Location

Central Coast Medical Oncology

Santa Maria, California, 93454, United States

Location

UCLA Hematology/Oncology

Santa Monica, California, 90404, United States

Location

Memorial Cancer Institute

Hollywood, Florida, 33021, United States

Location

Md Anderson Cancer Center Orlando

Orlando, Florida, 32806, United States

Location

New England Cancer Specialists

Scarborough, Maine, 04074, United States

Location

Comprehensive Cancer Centers of Nevada - Henderson

Henderson, Nevada, 89052, United States

Location

ProHEALTH Care Associates LLP

Lake Success, New York, 11042, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Hope A Women's Cancer Center

Asheville, North Carolina, 28806, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Roper Bon Secours St. Francis Cancer Center

Charleston, South Carolina, 29414, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Clinique Saint-Joseph

Liège, 4000, Belgium

Location

Clinique Ste-Elisabeth, Pharmacie

Namur, 5000, Belgium

Location

Sint Augustinus Wilrijk

Wilrijk, 2610, Belgium

Location

Cross Cancer Institute ; Dept of Medical Oncology

Edmonton, Alberta, T6G 1Z2, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael'S Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Chum Hospital Notre Dame

Montreal, Quebec, H2L 4M1, Canada

Location

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

Montreal, Quebec, H3T 1E2, Canada

Location

CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY

Québec, G1S 4L8, Canada

Location

Ico - Paul Papin

Angers, 49000, France

Location

HOPITAL JEAN MINJOZ; Oncologie

Besançon, 25030, France

Location

Hopital Morvan

Brest, 29200, France

Location

CHD Les Oudairies

La Roche-sur-Yon, 85925, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Centre Catherine De Sienne

Nantes, 44202, France

Location

Centre Rene Gauducheau

Saint-Herblain, 44805, France

Location

Nouvel Hopital Civil - CHU Strasbourg

Strasbourg, 67091, France

Location

Klinikum Sindelfingen-Böblingen; Frauenklinik

Böblingen, 71032, Germany

Location

Luisenkrankenhaus GmbH, Brustzentrum

Düsseldorf, 40235, Germany

Location

Universitätsklinikum Erlangen; Frauenklinik

Erlangen, 91054, Germany

Location

Universitätsklinikum Mainz

Mainz, 55131, Germany

Location

Interdisziplinäres Onkologisches Zentrum

München, 80336, Germany

Location

Moscow City Oncology Hospital #62

Moscovskaya Oblast, Moscow Oblast, 143423, Russia

Location

Regional Oncology Hospital Of Kursk; Chemotherapy

Kislino, Kursk Region, 305524, Russia

Location

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

Moscow, 115478, Russia

Location

State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis

Orenburg, 460021, Russia

Location

Saint-Petersburg City Clinical Oncology Dispensary

Saint Petersburg, 197022, Russia

Location

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

Saratov, 410004, Russia

Location

National Cancer Center

Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center - Oncology

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, 08208, Spain

Location

IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital Universitari de Lleida Arnau de Vilanova

Lleida, Lerida, 25198, Spain

Location

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

A Coruña, 15006, Spain

Location

Hospital Nuestra Señora de Sonsoles; servicio de Oncologia

Ávila, 05071, Spain

Location

Hospital del Mar; Servicio de Oncologia

Barcelona, 08003, Spain

Location

Fundacio Santa Creu I Sant Pau

Barcelona, 08006, Spain

Location

Complejo Hospitalario de Jaen

Jaén, 23007, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, 28007, Spain

Location

Hospital Universitario Clínico San Carlos; Servicio de Oncologia

Madrid, 28040, Spain

Location

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, 28050, Spain

Location

Hospital Quiron de Madrid; Servicio de Oncologia

Madrid, 28223, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, 50009, Spain

Location

Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery

Kaohsiung City, 807, Taiwan

Location

National Taiwan Uni Hospital

Taipei, 10041, Taiwan

Location

Mackay Memorial Hospital; Dept of Surgery

Taipei, 104, Taiwan

Location

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

Taipei, 112, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

Cherkassy Regional Oncological Hospital

Cherkassy, 18009, Ukraine

Location

State Medical Academy; Oncology

Dnipropetrovsk, 43102, Ukraine

Location

Karkiv Regional Oncology Center

Kharkiv, 61070, Ukraine

Location

Lvov State Regional Center

Lviv, 79031, Ukraine

Location

Related Publications (3)

• 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.

  PMID: 36631725 DERIVED

• 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.

  PMID: 31157583 DERIVED

• 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.

  PMID: 29175149 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Carboplatin; Docetaxel; pertuzumab; Trastuzumab; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Maytansine; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

The reported results are interim only.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2014
• First Posted: May 6, 2014
• Study Start: June 25, 2014
• Primary Completion: December 31, 2015
• Study Completion: May 29, 2018
• Last Updated: July 2, 2019
• Results First Posted: June 8, 2017

Record last verified: 2019-06

Locations

ES (16); BE (5); FR (9); TW (6); DE (5); RU (6); UA (4); KR (6); CA (6); US (16)