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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00950300




Registration number
NCT00950300
Ethics application status
Date submitted
30/07/2009
Date registered
31/07/2009
Date last updated
23/01/2018

Titles & IDs
Public title
A Study to Compare Subcutaneous (SC) Versus Intravenous (IV) Administration of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer
Scientific title
A Phase III, Randomized Open-Label Study to Compare the Pharmacokinetics, Efficacy, and Safety of Subcutaneous (SC) Trastuzumab With Intravenous (IV) Trastuzumab Administered in Women With HER2-Positive Early Breast Cancer (EBC)
Secondary ID [1] 0 0
2008-007326-19
Secondary ID [2] 0 0
BO22227
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 5-Fluorouracil
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Docetaxel
Treatment: Drugs - Epirubicin
Treatment: Drugs - Herceptin IV [trastuzumab]
Treatment: Drugs - Herceptin SC [trastuzumab]

Active Comparator: Herceptin IV + Chemotherapy - Participants will receive Herceptin via IV infusion for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin IV will be given on Day 1 of each 21-day cycle, as 8 milligrams per kilogram (mg/kg) for a loading dose during Cycle 1 and as 6 mg/kg during subsequent cycles.

Experimental: Herceptin SC + Chemotherapy - Participants will receive Herceptin via SC injection for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin SC will be given on Day 1 of each 21-day cycle, as a 600-milligram (mg) fixed dose.


Treatment: Drugs: 5-Fluorouracil
Participants will receive 5-fluorouracil, 500 milligrams per meter-squared (mg/m^2) via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Treatment: Drugs: Cyclophosphamide
Participants will receive cyclophosphamide, 500 mg/m^2 via IV bolus, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Treatment: Drugs: Docetaxel
Participants will receive docetaxel, 75 mg/m^2 via IV infusion on Day 1 of every 21-day cycle during Cycles 1 to 4.

Treatment: Drugs: Epirubicin
Participants will receive epirubicin, 75 mg/m^2 via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Treatment: Drugs: Herceptin IV [trastuzumab]
Herceptin will be administered as 8 mg/kg (loading dose during Cycle 1) and 6 mg/kg (subsequent cycles) via IV infusion on Day 1 of each 21-day cycle for a total of 18 cycles.

Treatment: Drugs: Herceptin SC [trastuzumab]
Herceptin will be administered as fixed dose 600 mg SC on Day 1 of each 21-day cycle for a total of 18 cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery
Timepoint [1] 0 0
Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Primary outcome [2] 0 0
Percentage of Participants With Pathological Complete Response (pCR)
Timepoint [2] 0 0
After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)
Secondary outcome [1] 0 0
Observed Ctrough of Trastuzumab After Surgery
Timepoint [1] 0 0
Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
Secondary outcome [2] 0 0
Predicted Ctrough of Trastuzumab Prior to Surgery
Timepoint [2] 0 0
Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Secondary outcome [3] 0 0
Predicted Ctrough of Trastuzumab After Surgery
Timepoint [3] 0 0
Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
Secondary outcome [4] 0 0
Number of Participants With Ctrough of Trastuzumab >20 µg/mL Prior to Surgery
Timepoint [4] 0 0
Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Secondary outcome [5] 0 0
Number of Participants With Ctrough of Trastuzumab >20 µg/mL After Surgery
Timepoint [5] 0 0
Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
Secondary outcome [6] 0 0
Maximum Serum Concentration (Cmax) of Trastuzumab Prior to Surgery
Timepoint [6] 0 0
Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Secondary outcome [7] 0 0
Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to Surgery
Timepoint [7] 0 0
Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Secondary outcome [8] 0 0
Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to Surgery
Timepoint [8] 0 0
Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
Secondary outcome [9] 0 0
Cmax of Trastuzumab After Surgery
Timepoint [9] 0 0
Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
Secondary outcome [10] 0 0
Tmax of Trastuzumab After Surgery
Timepoint [10] 0 0
Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
Secondary outcome [11] 0 0
AUC21d of Trastuzumab After Surgery
Timepoint [11] 0 0
Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
Secondary outcome [12] 0 0
Percentage of Participants With Total Pathological Complete Response (tpCR)
Timepoint [12] 0 0
After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)
Secondary outcome [13] 0 0
Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0, Among Those With Measurable Disease at Baseline
Timepoint [13] 0 0
Tumor assessments at Baseline; on Day 1 of Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months overall)
Secondary outcome [14] 0 0
Time to Response According to RECIST Version 1.0, Among Those With Measurable Disease at Baseline
Timepoint [14] 0 0
Tumor assessments at Baseline; on Day 1 Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of chemotherapy (approximately 6 months overall)
Secondary outcome [15] 0 0
Percentage of Participants Who Experienced a Protocol-Defined Event
Timepoint [15] 0 0
Screening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
Secondary outcome [16] 0 0
Event-Free Survival (EFS)
Timepoint [16] 0 0
Screening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
Secondary outcome [17] 0 0
Percentage of Participants Who Died
Timepoint [17] 0 0
Continuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
Secondary outcome [18] 0 0
Overall Survival (OS)
Timepoint [18] 0 0
Continuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
Secondary outcome [19] 0 0
Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab
Timepoint [19] 0 0
Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18
Secondary outcome [20] 0 0
Number of Participants With ADAs Against Recombinant Human Hyaluronidase (rHuPH20)
Timepoint [20] 0 0
Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18

Eligibility
Key inclusion criteria
* Adult women greater than or equal to (=) 18 years of age
* Non-metastatic primary invasive adenocarcinoma of the breast clinical stage I to IIIC, including inflammatory and multicentric/multifocal breast cancer, with tumor size =1 centimeter (cm) by ultrasound or =2 cm by palpation, centrally confirmed HER2-positive (immunohistochemical score [IHC] 3+ or in situ hybridization [ISH]-positive)
* At least 1 measurable lesion in breast or lymph nodes (=1 cm by ultrasound or =2 cm by palpation), except for inflammatory carcinoma (T4d)
* Baseline left ventricular ejection fraction (LVEF) =55%
* Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
* Adequate organ function at Baseline
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma
* Past or current history of malignant neoplasms, except for curatively treated basal and squamous cell carcinoma of the skin and in situ carcinoma of the cervix
* Metastatic disease
* Any prior therapy with anthracyclines
* Prior anti-HER2 therapy or biologic or immunotherapy
* Serious cardiac illness
* Pregnant or lactating women

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 3
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
16/10/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/01/2017
Sample size
Target
Accrual to date
Final
596
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Tucuman
Country [2] 0 0
Brazil
State/province [2] 0 0
BA
Country [3] 0 0
Brazil
State/province [3] 0 0
PR
Country [4] 0 0
Brazil
State/province [4] 0 0
RN
Country [5] 0 0
Brazil
State/province [5] 0 0
SC
Country [6] 0 0
Brazil
State/province [6] 0 0
SP
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Colombia
State/province [8] 0 0
Bogota
Country [9] 0 0
Colombia
State/province [9] 0 0
Pereira
Country [10] 0 0
Czechia
State/province [10] 0 0
Olomouc
Country [11] 0 0
Czechia
State/province [11] 0 0
Pardubice
Country [12] 0 0
Czechia
State/province [12] 0 0
Praha
Country [13] 0 0
Estonia
State/province [13] 0 0
Tallinn
Country [14] 0 0
Estonia
State/province [14] 0 0
Tartu
Country [15] 0 0
France
State/province [15] 0 0
Besancon
Country [16] 0 0
France
State/province [16] 0 0
Grenoble
Country [17] 0 0
France
State/province [17] 0 0
La Tronche
Country [18] 0 0
France
State/province [18] 0 0
Le Mans
Country [19] 0 0
France
State/province [19] 0 0
Paris
Country [20] 0 0
France
State/province [20] 0 0
Reims
Country [21] 0 0
France
State/province [21] 0 0
St Cloud
Country [22] 0 0
Germany
State/province [22] 0 0
Berlin
Country [23] 0 0
Germany
State/province [23] 0 0
Bonn
Country [24] 0 0
Germany
State/province [24] 0 0
Dortmund
Country [25] 0 0
Germany
State/province [25] 0 0
Hannover
Country [26] 0 0
Germany
State/province [26] 0 0
Leipzig
Country [27] 0 0
Germany
State/province [27] 0 0
Lemgo
Country [28] 0 0
Germany
State/province [28] 0 0
Offenbach
Country [29] 0 0
Germany
State/province [29] 0 0
Rodewisch
Country [30] 0 0
Germany
State/province [30] 0 0
Tübingen
Country [31] 0 0
Guatemala
State/province [31] 0 0
Guatemala
Country [32] 0 0
Hong Kong
State/province [32] 0 0
Hong Kong
Country [33] 0 0
Hungary
State/province [33] 0 0
Budapest
Country [34] 0 0
Hungary
State/province [34] 0 0
Gyor
Country [35] 0 0
Hungary
State/province [35] 0 0
Szeged
Country [36] 0 0
Israel
State/province [36] 0 0
Jerusalem
Country [37] 0 0
Israel
State/province [37] 0 0
Petach Tikva
Country [38] 0 0
Italy
State/province [38] 0 0
Campania
Country [39] 0 0
Italy
State/province [39] 0 0
Lombardia
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Incheon
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Seoul
Country [42] 0 0
Mexico
State/province [42] 0 0
Obregon
Country [43] 0 0
Mexico
State/province [43] 0 0
Toluca
Country [44] 0 0
Panama
State/province [44] 0 0
Panama
Country [45] 0 0
Peru
State/province [45] 0 0
Arequipa
Country [46] 0 0
Peru
State/province [46] 0 0
Lima
Country [47] 0 0
Peru
State/province [47] 0 0
Piura
Country [48] 0 0
Peru
State/province [48] 0 0
San Isidro
Country [49] 0 0
Poland
State/province [49] 0 0
Elblag
Country [50] 0 0
Poland
State/province [50] 0 0
Lublin
Country [51] 0 0
Poland
State/province [51] 0 0
Olsztyn
Country [52] 0 0
Poland
State/province [52] 0 0
Warszawa
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Leningrad
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Ivanovo
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Moscow
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Pyatigorsk
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Ryazan
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Samara
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Saratov
Country [60] 0 0
Russian Federation
State/province [60] 0 0
St Petersburg
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Stavropol
Country [62] 0 0
Russian Federation
State/province [62] 0 0
Tula
Country [63] 0 0
Russian Federation
State/province [63] 0 0
Vladimir
Country [64] 0 0
Slovakia
State/province [64] 0 0
Kosice
Country [65] 0 0
Slovakia
State/province [65] 0 0
Poprad
Country [66] 0 0
South Africa
State/province [66] 0 0
Bloemfontein
Country [67] 0 0
South Africa
State/province [67] 0 0
Cape Town
Country [68] 0 0
South Africa
State/province [68] 0 0
Parktown, Johannesburg
Country [69] 0 0
South Africa
State/province [69] 0 0
Pretoria
Country [70] 0 0
South Africa
State/province [70] 0 0
Rondebosch
Country [71] 0 0
South Africa
State/province [71] 0 0
Sandton
Country [72] 0 0
Spain
State/province [72] 0 0
LA Coruña
Country [73] 0 0
Spain
State/province [73] 0 0
Tarragona
Country [74] 0 0
Spain
State/province [74] 0 0
Madrid
Country [75] 0 0
Spain
State/province [75] 0 0
Valencia
Country [76] 0 0
Spain
State/province [76] 0 0
Zaragoza
Country [77] 0 0
Sweden
State/province [77] 0 0
Lund
Country [78] 0 0
Sweden
State/province [78] 0 0
Uppsala
Country [79] 0 0
Taiwan
State/province [79] 0 0
Changhua
Country [80] 0 0
Taiwan
State/province [80] 0 0
Taipei City
Country [81] 0 0
Taiwan
State/province [81] 0 0
Taipei
Country [82] 0 0
Taiwan
State/province [82] 0 0
Taoyuan
Country [83] 0 0
Thailand
State/province [83] 0 0
Bangkok
Country [84] 0 0
Thailand
State/province [84] 0 0
Songkhla
Country [85] 0 0
Turkey
State/province [85] 0 0
Antalya
Country [86] 0 0
Turkey
State/province [86] 0 0
Istanbul
Country [87] 0 0
Turkey
State/province [87] 0 0
Izmir
Country [88] 0 0
Turkey
State/province [88] 0 0
Sihhiye, Ankara

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

Ethics approval
Ethics application status

Summary
Brief summary
In this open-label multicenter trial, participants with operable or locally advanced breast cancer will be randomized to pre-operative treatment with 8 cycles of chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil, epirubicin, and cyclophosphamide) concurrent with either SC Herceptin or IV Herceptin. After surgery, participants will receive a further 10 cycles of SC or IV Herceptin as per randomization to complete 1 year of treatment. All cycles will be 21 days in length. After the end of study treatment, participants will be followed for safety and efficacy for up to 5 years or until disease recurrence, whichever is earlier.
Trial website
https://clinicaltrials.gov/study/NCT00950300
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

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/NCT00950300