Clinical trial NCT00545688: A Study of Pertuzumab in Combination With Herceptin in Patients With HER2 Positive Breast Cancer.
Official title: A Randomized, Open Label Study to Compare the Complete Pathological Response Rate Achieved With 4 Combinations of Herceptin, Docetaxel and Pertuzumab in Patients With Locally Advanced, Inflammatory or Early Stage HER2 Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2007-10-17
Enrollment: 417
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percentage of Participants Achieving Pathological Complete Response (pCR)
timeFrame: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
measure: Percentage of Participants Achieving pCR by Breast Cancer Type
timeFrame: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
measure: Percentage of Participants Achieving pCR by Hormone Receptor Status
timeFrame: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
measure: Percentage of Participants Achieving pCR by Lymph Node Status
timeFrame: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
measure: Percentage of Participants Achieving pCR by Presence or Absence of Residual Intraductal Carcinoma (DCIS) / Intalobular Carcinoma (LCIS)
timeFrame: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Secondary outcomes:
measure: 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
timeFrame: Baseline up to Cycle 4 (assessed at, Baseline and Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
measure: Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography
timeFrame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
measure: Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination
timeFrame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
measure: Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination
timeFrame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
measure: Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by X-Ray/Mammography
timeFrame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
measure: Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by Clinical Examination
timeFrame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
measure: Time to Clinical Response During Neo-Adjuvant Treatment Period
timeFrame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
measure: Percentage of Participants With Progressive Disease During Neo-Adjuvant Treatment Period
timeFrame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
measure: Percentage of Participants Achieving Breast Conserving Surgery For Whom Mastectomy Was Planned
timeFrame: Surgery (Within 2 weeks after Cycle 4) Up to approximately 24 months
measure: Percentage of Participants Who Were Progression Free and Disease Free
timeFrame: Randomization up to a maximum of 329 weeks
measure: Progression Free and Disease Free Survival
timeFrame: Randomization up to a maximum of 329 weeks
Other outcomes:
Locations:
city: Geelong
country: Australia
facility: Geelong Hospital; Andrew Love Cancer Centre
state: Victoria
city: Perth
country: Australia
facility: Mount Medical Center
state: Western Australia
city: Vienna
country: Austria
facility: Kaiser Franz Josef Spital; Iii. Medizinische Abt. Mit Onkologie
city: Wien
country: Austria
facility: Medizinische Universität Wien; Univ.Klinik für Innere Medizin I
city: Ijui
country: Brazil
facility: Hospital de Caridade de Ijui; Oncologia
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: RS
city: Itajai
country: Brazil
facility: Clinica de Neoplasias Litoral
state: SC
city: Jau
country: Brazil
facility: Hospital Amaral Carvalho
state: SP
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC - FMABC; Oncologia e Hematologia
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer Arnaldo Vieira de Carvalho - ICAVC; Pesquisa Clinica
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Perola Byington
state: SP
city: Sao Paulo
country: Brazil
facility: Inst. Brasileiro de Controle Ao Cancer; Oncologia Clinica / Quimioterapia
state: SP
city: Sorocaba
country: Brazil
facility: Instituto de Oncologia de Sorocaba - CEPOS
state: SP
city: Moncton
country: Canada
facility: Moncton Hospital
state: New Brunswick
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario; Kingston General Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network; Princess Margaret Hospital; Medical Oncology Dept
state: Ontario
city: Montreal
country: Canada
facility: McGill University; Montreal General Hosptial; Oncology
state: Quebec
city: Quebec
country: Canada
facility: CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hospital; Oncology Dept
city: Kfar-Saba
country: Israel
facility: Meir Medical Center; Oncology
city: Tel Aviv
country: Israel
facility: Sourasky / Ichilov Hospital; Dept. of Oncology
city: Bologna
country: Italy
facility: Az. Osp. S. Orsola Malpighi; Istituto Di Oncologia Seragnoli
state: Emilia-Romagna
city: Parma
country: Italy
facility: Ospedale Regionale Di Parma; Divisione Di Oncologia Medica
state: Emilia-Romagna
city: Udine
country: Italy
facility: Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia
state: Friuli-Venezia Giulia
city: Legnano
country: Italy
facility: ASST OVEST MILANESE; Oncologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Ospedale San Raffaele, Servizio di Oncologia e Chemioterapia
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
state: Lombardia
city: Mirano
country: Italy
facility: Ospedale Calvi di Noale; U.O. Complessa di Oncologia ed Ematologia Oncologica
state: Veneto
city: Santorso
country: Italy
facility: Polo Ospedaliero Santorso
state: Veneto
city: Vicenza
country: Italy
facility: Ospedale Di Vicenza; Nefrologia, Oncologia Medica
state: Veneto
city: Seoul
country: Korea, Republic of
facility: Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Centre; Division of Hematology/Oncology
city: Aguascalientes
country: Mexico
facility: Hospital Miguel Hidalgo
city: Mexico City
country: Mexico
facility: ARKE Estudios Clínicos S.A. de C.V.
city: Puebla
country: Mexico
facility: Issstep Puebla, ; Oncology
city: Arequipa
country: Peru
facility: Instituto Regional de Enfermedades Neoplásicas del Sur; Centro de Inv. de Medicina Oncológica
city: Lima
country: Peru
facility: Hospital Nacional Edgardo Rebagliati Martins; Oncologia
city: Lublin
country: Poland
facility: Samodzielny Publiczny Kliniczny Nr 1 W Lublinie; Klinika Chirurgii Onkologicznej
city: Lublin
country: Poland
facility: COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
city: Olsztyn
country: Poland
facility: Olsztyński Ośrodek Onkologiczny Kopernik sp. z o.o.
city: Poznan
country: Poland
facility: Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu
city: Poznan
country: Poland
facility: NZOZ Centrum Medyczne HCP Sp. z o.o.
city: Warszawa
country: Poland
facility: Central Hospital of Military School of Medicine; Oncology
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
city: St Petersburg
country: Russian Federation
facility: FSBI "Scientific Research Institute of Oncology named after N.N.Petrov" Ministry of Health of RF
state: Leningrad
city: Kazan
country: Russian Federation
facility: SI of Healthcare Kazan Oncology Dispensary
city: Moscow
country: Russian Federation
facility: Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy
city: Moscow
country: Russian Federation
facility: NSI of Healthcare Central Clinical Hospital #2 n.a. N.A.Semashko of the Russian Railways
city: Petrozavodsk
country: Russian Federation
facility: State Institution Of Healthcare Republican Oncology Dispensary
city: Pyatigorsk
country: Russian Federation
facility: State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary
city: Ryazan
country: Russian Federation
facility: SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF
city: Samara
country: Russian Federation
facility: SBI of Healthcare Samara Regional Clinical Oncology Dispensary
city: Soshi
country: Russian Federation
facility: SI of HealthCare Oncologic Dispensary #2 of department of healthcare of Krasnodar region
city: St Petersburg
country: Russian Federation
facility: SBI of Healthcare Leningrad Regional Oncology Dispensary
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Oncology Dispensary; Chemotherapy
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
state: Barcelona
city: Barakaldo
country: Spain
facility: Hospital de Cruces; Servicio de Oncologia
state: Vizcaya
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Oncologia
city: Stockholm
country: Sweden
facility: Karolinska Hospital; Oncology - Radiumhemmet
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset, Onkologkliniken
city: Baden
country: Switzerland
facility: Kantonsspital Baden; Frauenklinik
city: Zürich
country: Switzerland
facility: Brustzentrum
city: Taipei
country: Taiwan
facility: VETERANS GENERAL HOSPITAL; Department of General Surgery
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital; Dept of Oncology
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital; Medical Oncology
city: Bangkok
country: Thailand
facility: Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
city: Songkhla
country: Thailand
facility: Prince of Songkla Uni ; Unit of Medical Oncology
city: Izmir
country: Turkey
facility: Dokuz Eylul Uni Medical Faculty; Oncology Dept
city: Sıhhiye, ANKARA
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital; Oncology Dept
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital; Dept of Oncology
city: Manchester
country: United Kingdom
facility: Christie Hospital; Breast Cancer Research Office
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.