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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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) - 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
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 - 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.
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 - 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.
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 - 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.
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) - 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.
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 - Tumor assessments were made based upon the Response Evaluation Criteria in Solid Tumors (RECIST) criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for primary breast tumor using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is greater than (>)0 at screening or cycle 1 Day 1; PR: if measurement is at least a 30 percent (%) decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline.
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 - Tumor assessments were made based on the RECIST criteria - version 1.0 The overall response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined.
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 - Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for primary breast tumor using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined.
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 - Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined.
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 - Clinical response was determined based on tumor measurements by sponsor in combination with tumor response assessment by investigator. Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment. Overall response is derived based on the sum total of breast tumors and all nodes examined.
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 - Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment. Primary breast tumor clinical response is based on primary breast tumor assessment. Overall response is derived based on the sum total of breast tumors and all nodes examined.
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 - Time to clinical response was defined as the time from the date of first dose received to the date of assessment of clinical response. Time to Clinical response was determined by Kaplan-Meier estimates. Tumor assessments were made based on the RECIST criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment.
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 - Tumor assessments were made based upon the Response Evaluation Criteria in Solid Tumors (RECIST) criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: PD: if lesion is at least a 20 % increased from measurements at baseline. Percentage of participants along with 95% Confidence Interval (CI) for one sample binomial using Pearson-Clopper method were reported. Missing investigator assessments were considered as no progressive disease.
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 - Breast Conserving Surgery (BCS) was defined as quadrantectomy, lumpectomy, no surgery, sentinel node biopsy, axillary surgical resection or other method of avoiding mastectomy.
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 - Disease-free survival (DFS) was defined as the time from first date of no disease to first documentation of PD or death. Participants without progression after surgery were considered Disease Free. Any evidence of contralateral disease in-situ was not considered as PD. Participants who were withdrawn from the study without documented progression and for whom evaluations were made, were censored at date of last assessment when participant was known to be disease-free. Progression-free survival (PFS) was defined as time from date of randomization to first documentation of PD or death. Any evidence of contralateral disease in-situ was not considered as PD. Participants who were withdrawn from study without documented progression and for whom evaluations were made, were censored at date of last assessment when the participant was known to be free from progressive disease. Participants without post baseline assessments but known to be alive were censored at the time of randomization.
Timepoint [10] 0 0
Randomization up to a maximum of 329 weeks
Secondary outcome [11] 0 0
Progression Free and Disease Free Survival - DFS was defined as the time from the first date of no disease (date of surgery) to the first documentation of PD or death. Participants without progression after surgery were considered Disease Free. Any evidence of contralateral disease in-situ was not considered as PD. PFS was defined as the time from the date of randomization to the first documentation of PD or death. Any evidence of contralateral disease in-situ was not considered as PD. DFS and PFS were determined using Kaplan-Meier estimates.
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
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, 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
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)
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/show/NCT00545688
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