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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00545688




Registration number
NCT00545688
Ethics application status
Date submitted
16/10/2007
Date registered
17/10/2007
Date last updated
15/08/2017

Titles & IDs
Public title
A Study of Pertuzumab in Combination With Herceptin in Patients With HER2 Positive Breast Cancer.
Scientific 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
Secondary ID [1] 0 0
WO20697
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Herceptin
Treatment: Drugs - Docetaxel
Treatment: Drugs - Pertuzumab

Experimental: 1 -

Experimental: 2 -

Experimental: 3 -

Experimental: 4 -


Treatment: Drugs: Herceptin
8mg/kg iv loading dose, followed by 6mg/kg iv 3-weekly

Treatment: Drugs: Docetaxel
75mg/m2 iv escalating to 100mg/m2 iv 3-weekly

Treatment: Drugs: Pertuzumab
840mg iv loading dose, followed by 420mg iv 3-weekly
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving Pathological Complete Response (pCR)
Timepoint [1] 0 0
Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Primary outcome [2] 0 0
Percentage of Participants Achieving pCR by Breast Cancer Type
Timepoint [2] 0 0
Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Primary outcome [3] 0 0
Percentage of Participants Achieving pCR by Hormone Receptor Status
Timepoint [3] 0 0
Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Primary outcome [4] 0 0
Percentage of Participants Achieving pCR by Lymph Node Status
Timepoint [4] 0 0
Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Primary outcome [5] 0 0
Percentage of Participants Achieving pCR by Presence or Absence of Residual Intraductal Carcinoma (DCIS) / Intalobular Carcinoma (LCIS)
Timepoint [5] 0 0
Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline up to Cycle 4 (assessed at, Baseline and Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Secondary outcome [2] 0 0
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography
Timepoint [2] 0 0
Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Secondary outcome [3] 0 0
Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination
Timepoint [3] 0 0
Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Secondary outcome [4] 0 0
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination
Timepoint [4] 0 0
Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Secondary outcome [5] 0 0
Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by X-Ray/Mammography
Timepoint [5] 0 0
Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Secondary outcome [6] 0 0
Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by Clinical Examination
Timepoint [6] 0 0
Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Secondary outcome [7] 0 0
Time to Clinical Response During Neo-Adjuvant Treatment Period
Timepoint [7] 0 0
Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Secondary outcome [8] 0 0
Percentage of Participants With Progressive Disease During Neo-Adjuvant Treatment Period
Timepoint [8] 0 0
Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
Secondary outcome [9] 0 0
Percentage of Participants Achieving Breast Conserving Surgery For Whom Mastectomy Was Planned
Timepoint [9] 0 0
Surgery (Within 2 weeks after Cycle 4) Up to approximately 24 months
Secondary outcome [10] 0 0
Percentage of Participants Who Were Progression Free and Disease Free
Timepoint [10] 0 0
Randomization up to a maximum of 329 weeks
Secondary outcome [11] 0 0
Progression Free and Disease Free Survival
Timepoint [11] 0 0
Randomization up to a maximum of 329 weeks

Eligibility
Key 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+).
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/06/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/09/2014
Sample size
Target
Accrual to date
Final
417
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Geelong Hospital; Andrew Love Cancer Centre - Geelong
Recruitment hospital [2] 0 0
Mount Medical Center - Perth
Recruitment postcode(s) [1] 0 0
3220 - Geelong
Recruitment postcode(s) [2] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Vienna
Country [2] 0 0
Austria
State/province [2] 0 0
Wien
Country [3] 0 0
Brazil
State/province [3] 0 0
RS
Country [4] 0 0
Brazil
State/province [4] 0 0
SC
Country [5] 0 0
Brazil
State/province [5] 0 0
SP
Country [6] 0 0
Canada
State/province [6] 0 0
New Brunswick
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
Israel
State/province [9] 0 0
Jerusalem
Country [10] 0 0
Israel
State/province [10] 0 0
Kfar-Saba
Country [11] 0 0
Israel
State/province [11] 0 0
Tel Aviv
Country [12] 0 0
Italy
State/province [12] 0 0
Emilia-Romagna
Country [13] 0 0
Italy
State/province [13] 0 0
Friuli-Venezia Giulia
Country [14] 0 0
Italy
State/province [14] 0 0
Lombardia
Country [15] 0 0
Italy
State/province [15] 0 0
Veneto
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Seoul
Country [17] 0 0
Mexico
State/province [17] 0 0
Aguascalientes
Country [18] 0 0
Mexico
State/province [18] 0 0
Mexico City
Country [19] 0 0
Mexico
State/province [19] 0 0
Puebla
Country [20] 0 0
Peru
State/province [20] 0 0
Arequipa
Country [21] 0 0
Peru
State/province [21] 0 0
Lima
Country [22] 0 0
Poland
State/province [22] 0 0
Lublin
Country [23] 0 0
Poland
State/province [23] 0 0
Olsztyn
Country [24] 0 0
Poland
State/province [24] 0 0
Poznan
Country [25] 0 0
Poland
State/province [25] 0 0
Warszawa
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Leningrad
Country [27] 0 0
Russian Federation
State/province [27] 0 0
Kazan
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Moscow
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Petrozavodsk
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Pyatigorsk
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Ryazan
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Samara
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Soshi
Country [34] 0 0
Russian Federation
State/province [34] 0 0
St Petersburg
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Ulyanovsk
Country [36] 0 0
Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Spain
State/province [37] 0 0
Vizcaya
Country [38] 0 0
Spain
State/province [38] 0 0
Cordoba
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Spain
State/province [40] 0 0
Valencia
Country [41] 0 0
Spain
State/province [41] 0 0
Zaragoza
Country [42] 0 0
Sweden
State/province [42] 0 0
Stockholm
Country [43] 0 0
Sweden
State/province [43] 0 0
Uppsala
Country [44] 0 0
Switzerland
State/province [44] 0 0
Baden
Country [45] 0 0
Switzerland
State/province [45] 0 0
Zürich
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taipei
Country [47] 0 0
Thailand
State/province [47] 0 0
Bangkok
Country [48] 0 0
Thailand
State/province [48] 0 0
Songkhla
Country [49] 0 0
Turkey
State/province [49] 0 0
Izmir
Country [50] 0 0
Turkey
State/province [50] 0 0
Sihhiye, ANKARA
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Coventry
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00545688
Trial related presentations / publications
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.
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. Erratum In: Ann Oncol. 2018 Apr 1;29(4):1075. doi: 10.1093/annonc/mdx336. Ann Oncol. 2018 Jul 1;29(7):1607. doi: 10.1093/annonc/mdx802. Ann Oncol. 2019 Aug 1;30(8):1404. doi: 10.1093/annonc/mdy538.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00545688