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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00976989




Registration number
NCT00976989
Ethics application status
Date submitted
14/09/2009
Date registered
15/09/2009
Date last updated
6/02/2017

Titles & IDs
Public title
A Study of Pertuzumab in Combination With Herceptin and Chemotherapy in Participants With HER2-Positive Breast Cancer
Scientific title
A Randomised, Multicentre, Multinational Phase II Study to Evaluate Pertuzumab in Combination With Trastuzumab, Given Either Concomitantly or Sequentially With Standard Anthracycline-based Chemotherapy or Concomitantly With a Non-anthracycline-based Chemotherapy Regimen, as Neoadjuvant Therapy for Patients With Locally Advanced, Inflammatory or Early Stage HER2-positive Breast Cancer
Secondary ID [1] 0 0
2009-012019-17
Secondary ID [2] 0 0
BO22280
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 - Pertuzumab
Treatment: Drugs - Trastuzumab
Treatment: Drugs - FEC
Treatment: Drugs - Docetaxel
Treatment: Drugs - TCH

Experimental: T+P Concomitant Anthracycline-based chemotherapy - 5-Fluorouracil, epirubicin with cyclophosphamide (FEC), trastuzumab (T) and pertuzumab (P) every three weeks for three cycles, followed by docetaxel, trastuzumab and pertuzumab every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.

Experimental: T+P Sequential Anthracycline-based chemotherapy - FEC every three weeks for three cycles, followed by docetaxel, trastuzumab (T) and pertuzumab (P) every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 21 as adjuvant therapy post-surgery.

Experimental: T+P Concomitant Non-Anthracycline chemotherapy - Trastuzumab, carboplatin, docetaxel (TCH) and pertuzumab (P) every three weeks, for six cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.


Treatment: Drugs: Pertuzumab
840 mg loading dose intravenously (IV), then 420 mg IV 3-weekly.

Treatment: Drugs: Trastuzumab
8 mg/kg loading dose IV, then 6 mg/kg every 3 weeks.

Treatment: Drugs: FEC
5-fluorouracil 500 mg/m^2, epirubicin 100 mg/m^2 and cyclophosphamide 600 mg/m^2.

Treatment: Drugs: Docetaxel
75 mg/m^2 for the first dose; 100 mg/m^2 if no dose limiting toxicity occurs.

Treatment: Drugs: TCH
Trastuzumab followed by carboplatin at target area under the plasma concentration-time curve (AUC) 6 and docetaxel at a starting dose of 75 mg/m^2. All treatments were given every three weeks by the IV route.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety: Percentage of Participants With Symptomatic Cardiac Events as Assessed by the Investigator - Left ventricular systolic dysfunction (LVSD) as assessed by the Investigator, including Grade 3, 4 or 5 symptomatic LVSD with symptomatic cardiac events.
Timepoint [1] 0 0
From baseline up to approximately 3.5 years
Primary outcome [2] 0 0
Safety: Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Decline During Pre-operative (Neoadjuvant) Period - Percentage of participants with LVEF measures decline of = 10% from baseline and to a value of <50% during the pre-operative (neoadjuvant) period.
Timepoint [2] 0 0
From baseline up to approximately 18 weeks
Secondary outcome [1] 0 0
Efficacy: Percentage of Participants With Complete Pathological Response (pCR) - pCR is defined as the absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. pCR is evaluated after 6 cycles of treatment and surgery or following withdrawal from the study whichever occurs sooner.
Timepoint [1] 0 0
At surgery, after 18 weeks (6 cycles) of treatment
Secondary outcome [2] 0 0
Efficacy: Clinical Response Rate - Tumor response is defined as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) and is identified as per local practice. Clinical response rate is defined as the percentage of participants who achieve a response of CR or PR at any time pre-surgery. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by mammogram or magnetic resonance imaging (MRI) and clinical breast examination (CBE), CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions.
Timepoint [2] 0 0
During each 3-week cycle of 6 total cycles: up to 18 weeks
Secondary outcome [3] 0 0
Efficacy: Time to Clinical Response - Time to clinical response is defined as the time from the date of first dose received to the first date of assessment of clinical response. Clinical response is defined as a response of CR or PR at any time pre-surgery. Per RECIST v1.0 for target lesions and assessed by mammogram or MRI and CBE, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions.
Timepoint [3] 0 0
Up to 18 weeks
Secondary outcome [4] 0 0
Efficacy: Percentage of Participants Achieving Breast Conserving Surgery - This is the percentage of participants who achieved breast conserving surgery out of the intent-to-treat population without inflammatory breast cancer, as these participants received mastectomy irrespective of their response to neoadjuvant (pre-operative) treatment.
Timepoint [4] 0 0
At approximately 18 weeks
Secondary outcome [5] 0 0
Efficacy: Percentage of Participants Without an Overall Survival (OS) Event - Overall survival (OS) was defined as the time from randomization to the date of death from any cause. Participants who were alive or lost to follow-up were censored at the last known alive date. Participants with no post-baseline information were censored at the date of randomization plus one day.
Timepoint [5] 0 0
From baseline to end of study up to 5 years
Secondary outcome [6] 0 0
Efficacy: Percentage of Participants Without a Disease-Free Survival (DFS) Event - The DFS was defined as the time from the first date of no disease (i.e., date of surgery) to the first documentation of progressive disease (PD) or death. PD was assessed using RECIST v1.0 and MRI and CBE. It was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. Any evidence of contralateral disease in situ was not considered as PD. Participants who were withdrawn from the study without documented PD were censored at the date of the last assessment when the participant was known to be disease-free.
Timepoint [6] 0 0
From baseline to end of study up to 5 years
Secondary outcome [7] 0 0
Efficacy: Percentage of Participants Without a Progression-Free Survival (PFS) Event - Progression-free survival was defined as the time from the date of randomization to the first documentation of PD or death from any cause, whichever occurred first. PD was assessed using RECIST v1.0 and MRI and CBE. It was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. Participants who were withdrawn from the study without documented PD were censored at the date of the last assessment when the participant was known to be free from PD. Participants without post-baseline assessments but known to be alive were censored at the time of randomization plus one day.
Timepoint [7] 0 0
From baseline to end of study up to 5 years
Secondary outcome [8] 0 0
Safety: Percentage of Participants With Cardiac Symptoms Associated With Symptomatic Left Ventricular Systolic Dysfunction (LVSD) - Percentage of participants with signs or symptoms of cardiac events.
Timepoint [8] 0 0
From Baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years)
Secondary outcome [9] 0 0
Safety: Percentage of Participants With Asymptomatic Left Ventricular Ejection Fraction (LVEF) Events - Percentage of participants with LVEF events without signs or symptoms of cardiac events.
Timepoint [9] 0 0
From baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years)
Secondary outcome [10] 0 0
Safety: Maximum Decrease in Left Ventricular Ejection Fraction (LVEF) Measures - Maximum decrease in LVEF measures is the change from baseline at worst treatment value. LVEF is measured as percentage.
Timepoint [10] 0 0
From baseline up to approximately 3.5 years

Eligibility
Key inclusion criteria
- female participants, age >/=18 years

- advanced, inflammatory or early stage unilateral invasive breast cancer

- HER2-positive breast cancer

- baseline left ventricular ejection fraction (LVEF) >/=55%
Minimum age
18 Years
Maximum age
No limit
Gender
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, except for carcinoma in situ of the cervix, or basal cell carcinoma

- clinically relevant cardiovascular disease

- current chronic treatment with corticosteroids of >10mg methylprednisolone or
equivalent

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Bahamas
State/province [1] 0 0
Nassau
Country [2] 0 0
Bosnia and Herzegovina
State/province [2] 0 0
Banja Luka
Country [3] 0 0
Bosnia and Herzegovina
State/province [3] 0 0
Sarajevo
Country [4] 0 0
Brazil
State/province [4] 0 0
RS
Country [5] 0 0
Brazil
State/province [5] 0 0
SP
Country [6] 0 0
Canada
State/province [6] 0 0
British Columbia
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
Croatia
State/province [9] 0 0
Pula
Country [10] 0 0
Germany
State/province [10] 0 0
Heidelberg
Country [11] 0 0
Germany
State/province [11] 0 0
Kiel
Country [12] 0 0
Germany
State/province [12] 0 0
Regensburg
Country [13] 0 0
Germany
State/province [13] 0 0
Trier
Country [14] 0 0
Germany
State/province [14] 0 0
Troisdorf
Country [15] 0 0
Germany
State/province [15] 0 0
Ulm
Country [16] 0 0
Greece
State/province [16] 0 0
Heraklion
Country [17] 0 0
Greece
State/province [17] 0 0
Thessaloniki
Country [18] 0 0
Italy
State/province [18] 0 0
Lazio
Country [19] 0 0
Italy
State/province [19] 0 0
Lombardia
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Daegu
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul
Country [22] 0 0
Mexico
State/province [22] 0 0
Mexico City
Country [23] 0 0
Mexico
State/province [23] 0 0
Xalapa
Country [24] 0 0
New Zealand
State/province [24] 0 0
Auckland
Country [25] 0 0
Portugal
State/province [25] 0 0
Aveiro
Country [26] 0 0
Portugal
State/province [26] 0 0
Lisboa
Country [27] 0 0
Romania
State/province [27] 0 0
Bucharest
Country [28] 0 0
Romania
State/province [28] 0 0
Cluj Napoca
Country [29] 0 0
Romania
State/province [29] 0 0
Iasi
Country [30] 0 0
Serbia
State/province [30] 0 0
Belgrade
Country [31] 0 0
South Africa
State/province [31] 0 0
Durban
Country [32] 0 0
South Africa
State/province [32] 0 0
Pretoria
Country [33] 0 0
Spain
State/province [33] 0 0
Guipuzcoa
Country [34] 0 0
Spain
State/province [34] 0 0
Barcelona
Country [35] 0 0
Spain
State/province [35] 0 0
Cordoba
Country [36] 0 0
Spain
State/province [36] 0 0
Madrid
Country [37] 0 0
Sweden
State/province [37] 0 0
Eskilstuna
Country [38] 0 0
Sweden
State/province [38] 0 0
Stockholm
Country [39] 0 0
Sweden
State/province [39] 0 0
Sundsvall
Country [40] 0 0
Sweden
State/province [40] 0 0
Umea
Country [41] 0 0
Switzerland
State/province [41] 0 0
Baden
Country [42] 0 0
Switzerland
State/province [42] 0 0
Zürich
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taichung
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taipei
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Bournemouth
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Derby
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Guildford
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Newcastle Upon Tyne
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Southampton
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Truro
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Westcliffe-on-sea

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

Ethics approval
Ethics application status

Summary
Brief summary
This 3 arm study will assess the tolerability, safety and efficacy of 3 neoadjuvant treatment
regimens in participants with locally advanced, inflammatory or early stage human epidermal
growth factor receptor 2 (HER2)-positive breast cancer. Before surgery, participants will be
randomized to receive either A) 6 cycles of pertuzumab plus trastuzumab (Herceptin), with
5-fluorouracil/epirubicin/cyclophosphamide (FEC) for cycles 1-3 and docetaxel for cycles 4-6,
or B) FEC for cycles 1-3 followed by pertuzumab plus trastuzumab with docetaxel for cycles
4-6, or C) 6 cycles of pertuzumab plus trastuzumab with docetaxel and carboplatin. Pertuzumab
will be administered at a loading dose of 840 mg intravenously (iv), then 420 mg iv 3-weekly,
trastuzumab at a loading dose of 8 mg/kg iv, then 6 mg/kg iv 3-weekly, docetaxel at 75 mg/m^2
iv, increased to 100 mg/m^2 iv 3-weekly, and FEC and carboplatin iv 3-weekly at standard
doses. Following surgery participants will receive trastuzumab 6 mg/kg iv 3-weekly for a
total of 1 year, as well as adequate chemo-, radio- and hormone therapy. Anticipated time on
study treatment is 4-12 months, and target sample size is 200-300.
Trial website
https://clinicaltrials.gov/show/NCT00976989
Trial related presentations / publications
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
Other publications