A Study of Pertuzumab in Combination With Herceptin in Patients With HER2 Positive Breast Cancer.

NCT00545688 | Completed Phase 2 Results

• 1 other identifier: WO20697
• Study Type: interventional
• Target: 417
• Locations: 17 countries
• Sites: 75

Brief Summary

This 4 arm study will evaluate the efficacy and safety of 4 neoadjuvant treatment regimens in female patients with locally advanced, inflammatory or early stage HER2 positive breast cancer. Before surgery, patients will be randomized to one of 4 treatment arms, to receive 4 cycles of a)Herceptin + docetaxel b)Herceptin + docetaxel + pertuzumab c)Herceptin + pertuzumab or 4)pertuzumab + docetaxel. Pertuzumab will be administered at a loading dose of 840mg iv, then 420mg iv 3-weekly, Herceptin at a loading dose of 8mg/kg iv then 6mg/kg 3-weekly, and docetaxel at a dose of 75mg/m2 escalating to 100mg/m2 3-weekly. During the entire pre- and post-surgery period all patients will receive adequate chemotherapy as per standard of care, as well as any surgery and/or radiotherapy as required. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants Achieving Pathological Complete Response (pCR)

  pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants with invalid/missing pCR assessments were defined as non-responders

  Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)

• Percentage of Participants Achieving pCR by Breast Cancer Type

  pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Based on the type of breast cancer participants were categorized as those with 1. Operable breast cancer, 2. Inflammatory breast cancer and 3. Locally advanced breast cancer. Participants with invalid/missing pCR assessments were defined as non-responders.

  Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)

• Percentage of Participants Achieving pCR by Hormone Receptor Status

  pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants were classified as Estrogen and/or Progesterone positive (+ve), Estrogen and/or Progesterone negative (-ve) or receptor status unknown. Participants with invalid/missing pCR assessments were defined as non-responders.

  Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)

• Percentage of Participants Achieving pCR by Lymph Node Status

  pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Lymph node status was defined as either negative lymph node at surgery or positive lymph node at surgery. Participants with invalid/missing pCR assessments were defined as non-responders.

  Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)

• Percentage of Participants Achieving pCR by Presence or Absence of Residual Intraductal Carcinoma (DCIS) / Intalobular Carcinoma (LCIS)

  pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants with invalid/missing pCR assessments were defined as non-responders.

  Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)

Secondary Outcomes (11)

• Percentage of Participants Achieving Best Primary Tumor Response (Complete Response [CR], Partial Response [PR], Stable Disease [SD] or Disease Progression [PD]) During Neo-Adjuvant Treatment by X-Ray/Mammography

  Baseline up to Cycle 4 (assessed at, Baseline and Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months

• Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography

  Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months

• Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination

  Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months

• Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination

  Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months

• Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by X-Ray/Mammography

  Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months

Study Arms (4)

1

EXPERIMENTAL

Drug: Herceptin; Drug: Docetaxel

2

EXPERIMENTAL

Drug: Herceptin; Drug: Docetaxel; Drug: Pertuzumab

3

EXPERIMENTAL

Drug: Herceptin; Drug: Pertuzumab

4

EXPERIMENTAL

Drug: Docetaxel; Drug: Pertuzumab

Interventions

Herceptin DRUG

8mg/kg iv loading dose, followed by 6mg/kg iv 3-weekly

Also known as: Trastuzumab

1; 2; 3

Docetaxel DRUG

75mg/m2 iv escalating to 100mg/m2 iv 3-weekly

1; 2; 4

Pertuzumab DRUG

840mg iv loading dose, followed by 420mg iv 3-weekly

2; 3; 4

Eligibility Criteria

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

You may qualify if:

• female patients, \>=18 years of age;
• locally advanced, inflammatory or early stage invasive breast cancer;
• HER2 positive (HER2+++ by IHC or FISH/CISH+).

You may not qualify if:

• metastatic disease (Stage IV) or bilateral breast cancer;
• previous anticancer therapy or radiotherapy for any malignancy;
• other malignancy, other than cancer in situ of the cervix, or basal cell cancer;
• insulin-dependent diabetes;
• clinically relevant cardiovascular disease.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (77)

Geelong Hospital; Andrew Love Cancer Centre

Geelong, Victoria, 3220, Australia

Location

Mount Medical Center

Perth, Western Australia, 6000, Australia

Location

Medizinische Universität Wien; Univ.Klinik für Innere Medizin I

Vienna, 1090, Austria

Location

Kaiser Franz Josef Spital; Iii. Medizinische Abt. Mit Onkologie

Vienna, 1100, Austria

Location

Hospital de Caridade de Ijui; Oncologia

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Clinica de Neoplasias Litoral

Itajaí, Santa Catarina, 88301-220, Brazil

Location

Hospital Amaral Carvalho

Jaú, São Paulo, 17210-080, Brazil

Location

Faculdade de Medicina do ABC - FMABC; Oncologia e Hematologia

Santo André, São Paulo, 09060-650, Brazil

Location

Instituto do Cancer Arnaldo Vieira de Carvalho - ICAVC; Pesquisa Clinica

São Paulo, São Paulo, 01221-020, Brazil

Location

Hospital Perola Byington

São Paulo, São Paulo, 01317-000, Brazil

Location

Inst. Brasileiro de Controle Ao Cancer; Oncologia Clinica / Quimioterapia

São Paulo, São Paulo, 03102-002, Brazil

Location

Instituto de Oncologia de Sorocaba - CEPOS

Sorocaba, São Paulo, 18030-245, Brazil

Location

Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Cancer Centre of Southeastern Ontario; Kingston General Hospital

Kingston, Ontario, K7L 5P9, Canada

Location

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University; Montreal General Hosptial; Oncology

Montreal, Quebec, H3G 1A4, Canada

Location

CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY

Québec, G1S 4L8, Canada

Location

Hadassah Ein Karem Hospital; Oncology Dept

Jerusalem, 91120-01, Israel

Location

Meir Medical Center; Oncology

Kfar Saba, 4428164, Israel

Location

Sourasky / Ichilov Hospital; Dept. of Oncology

Tel Aviv, 6423906, Israel

Location

Az. Osp. S. Orsola Malpighi; Istituto Di Oncologia Seragnoli

Bologna, Emilia-Romagna, 40138, Italy

Location

Ospedale Regionale Di Parma; Divisione Di Oncologia Medica

Parma, Emilia-Romagna, 43100, Italy

Location

Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia

Udine, Friuli Venezia Giulia, 33100, Italy

Location

ASST OVEST MILANESE; Oncologia Medica

Legnano, Lombardy, 20025, Italy

Location

Ospedale San Raffaele, Servizio di Oncologia e Chemioterapia

Milan, Lombardy, 20132, Italy

Location

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1

Milan, Lombardy, 20133, Italy

Location

Ospedale Calvi di Noale; U.O. Complessa di Oncologia ed Ematologia Oncologica

Mirano, Veneto, 30035, Italy

Location

Polo Ospedaliero Santorso

Santorso, Veneto, 36014, Italy

Location

Ospedale Di Vicenza; Nefrologia, Oncologia Medica

Vicenza, Veneto, 36100, Italy

Location

Hospital Miguel Hidalgo

Aguascalientes, 20230, Mexico

Location

ARKE Estudios Clínicos S.A. de C.V.

Mexico City, 06700, Mexico

Location

Issstep Puebla, ; Oncology

Puebla City, 72530, Mexico

Location

Instituto Regional de Enfermedades Neoplásicas del Sur; Centro de Inv. de Medicina Oncológica

Arequipa, 5154, Peru

Location

Hospital Nacional Edgardo Rebagliati Martins; Oncologia

Lima, 11, Peru

Location

Samodzielny Publiczny Kliniczny Nr 1 W Lublinie; Klinika Chirurgii Onkologicznej

Lublin, 20-081, Poland

Location

COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

Lublin, 20-090, Poland

Location

Olsztyński Ośrodek Onkologiczny Kopernik sp. z o.o.

Olsztyn, 10-513, Poland

Location

Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu

Poznan, 60-569, Poland

Location

NZOZ Centrum Medyczne HCP Sp. z o.o.

Poznan, 61-485, Poland

Location

Central Hospital of Military School of Medicine; Oncology

Warsaw, 00-909, Poland

Location

Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii

Warsaw, 02-781, Poland

Location

FSBI "Scientific Research Institute of Oncology named after N.N.Petrov" Ministry of Health of RF

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

SI of Healthcare Kazan Oncology Dispensary

Kazan', 420111, Russia

Location

Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy

Moscow, 115478, Russia

Location

NSI of Healthcare Central Clinical Hospital #2 n.a. N.A.Semashko of the Russian Railways

Moscow, 129128, Russia

Location

State Institution Of Healthcare Republican Oncology Dispensary

Petrozavodsk, 185007, Russia

Location

State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary

Pyatigorsk, 357502, Russia

Location

SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF

Ryazan, 390011, Russia

Location

SBI of Healthcare Leningrad Regional Oncology Dispensary

Saint Petersburg, 191104, Russia

Location

SBI of Healthcare Samara Regional Clinical Oncology Dispensary

Samara, 443031, Russia

Location

SI of HealthCare Oncologic Dispensary #2 of department of healthcare of Krasnodar region

Sashi, 354057, Russia

Location

Ulyanovsk Regional Oncology Dispensary; Chemotherapy

Ulyanovsk, ND, Russia

Location

Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology

Seoul, 03080, South Korea

Location

Samsung Medical Centre; Division of Hematology/Oncology

Seoul, 135-710, South Korea

Location

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, 08208, Spain

Location

Hospital de Cruces; Servicio de Oncologia

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, 14004, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, 28007, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, 28046, Spain

Location

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, 46010, Spain

Location

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, 50009, Spain

Location

Karolinska Hospital; Oncology - Radiumhemmet

Stockholm, 17176, Sweden

Location

Akademiska sjukhuset, Onkologkliniken

Uppsala, 75185, Sweden

Location

Kantonsspital Baden; Frauenklinik

Baden, 5405, Switzerland

Location

Brustzentrum

Zurich, 8008, Switzerland

Location

VETERANS GENERAL HOSPITAL; Department of General Surgery

Taipei, 00112, Taiwan

Location

National Taiwan Uni Hospital; Dept of Oncology

Taipei, 100, Taiwan

Location

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

Taipei, 112, Taiwan

Location

Chulalongkorn Hospital; Medical Oncology

Bangkok, 10330, Thailand

Location

Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology

Bangkok, 10700, Thailand

Location

Prince of Songkla Uni ; Unit of Medical Oncology

Songkhla, 90110, Thailand

Location

Dokuz Eylul Uni Medical Faculty; Oncology Dept

Izmir, 35340, Turkey (Türkiye)

Location

Hacettepe Uni Medical Faculty Hospital; Oncology Dept

Sıhhiye, Ankara, 06100, Turkey (Türkiye)

Location

Walsgrave Hospital; Dept of Oncology

Coventry, CV2 2DX, United Kingdom

Location

Christie Hospital; Breast Cancer Research Office

Manchester, M20 4QL, United Kingdom

Location

Related Publications (4)

• Bianchini G, Kiermaier A, Bianchi GV, Im YH, Pienkowski T, Liu MC, Tseng LM, Dowsett M, Zabaglo L, Kirk S, Szado T, Eng-Wong J, Amler LC, Valagussa P, Gianni L. Biomarker analysis of the NeoSphere study: pertuzumab, trastuzumab, and docetaxel versus trastuzumab plus docetaxel, pertuzumab plus trastuzumab, or pertuzumab plus docetaxel for the neoadjuvant treatment of HER2-positive breast cancer. Breast Cancer Res. 2017 Feb 9;19(1):16. doi: 10.1186/s13058-017-0806-9.

  PMID: 28183321 DERIVED

• Swain SM, Schneeweiss A, Gianni L, Gao JJ, Stein A, Waldron-Lynch M, Heeson S, Beattie MS, Yoo B, Cortes J, Baselga J. Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab. Ann Oncol. 2017 Apr 1;28(4):761-768. doi: 10.1093/annonc/mdw695.

  PMID: 28057664 DERIVED

• Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazzu D, McNally V, Douthwaite H, Ross G, Valagussa P. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800. doi: 10.1016/S1470-2045(16)00163-7. Epub 2016 May 11.

  PMID: 27179402 DERIVED

• Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. doi: 10.1016/S1470-2045(11)70336-9. Epub 2011 Dec 6.

  PMID: 22153890 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Docetaxel; pertuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmannb-LaRoche

genentech@druginfo.com

1-800-821-8590

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2007
• First Posted: October 17, 2007
• Study Start: June 26, 2006
• Primary Completion: September 22, 2014
• Study Completion: September 22, 2014
• Last Updated: August 15, 2017
• Results First Posted: January 26, 2016

Record last verified: 2017-07

Locations

BR (9); IL (3); IT (9); PL (7); SE (2); AU (2); CH (2); CA (5); ME (3); TW (3); TH (3); RU (11); KR (2); TU (2); PE (2); GB (2); ES (8)