Clinical trial NCT00976989: A Study of Pertuzumab in Combination With Herceptin and Chemotherapy in Participants With HER2-Positive Breast Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-09-15
Enrollment: 225
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 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.


Eligibility criteria: 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%

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

Primary outcomes:
measure: Safety: Percentage of Participants With Symptomatic Cardiac Events as Assessed by the Investigator
timeFrame: From baseline up to approximately 3.5 years
measure: Safety: Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Decline During Pre-operative (Neoadjuvant) Period
timeFrame: From baseline up to approximately 18 weeks
Secondary outcomes:
measure: Efficacy: Percentage of Participants With Complete Pathological Response (pCR)
timeFrame: At surgery, after 18 weeks (6 cycles) of treatment
measure: Efficacy: Clinical Response Rate
timeFrame: During each 3-week cycle of 6 total cycles: up to 18 weeks
measure: Efficacy: Time to Clinical Response
timeFrame: Up to 18 weeks
measure: Efficacy: Percentage of Participants Achieving Breast Conserving Surgery
timeFrame: At approximately 18 weeks
measure: Efficacy: Percentage of Participants Without an Overall Survival (OS) Event
timeFrame: From baseline to end of study up to 5 years
measure: Efficacy: Percentage of Participants Without a Disease-Free Survival (DFS) Event
timeFrame: From baseline to end of study up to 5 years
measure: Efficacy: Percentage of Participants Without a Progression-Free Survival (PFS) Event
timeFrame: From baseline to end of study up to 5 years
measure: Safety: Percentage of Participants With Cardiac Symptoms Associated With Symptomatic Left Ventricular Systolic Dysfunction (LVSD)
timeFrame: 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)
measure: Safety: Percentage of Participants With Asymptomatic Left Ventricular Ejection Fraction (LVEF) Events
timeFrame: 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)
measure: Safety: Maximum Decrease in Left Ventricular Ejection Fraction (LVEF) Measures
timeFrame: From baseline up to approximately 3.5 years
Other outcomes:
Locations:
city: Nassau
country: Bahamas
city: Banja Luka
country: Bosnia and Herzegovina
city: Sarajevo
country: Bosnia and Herzegovina
city: Porto Alegre
country: Brazil
state: RS
city: Sao Paulo
country: Brazil
state: SP
city: Vancouver
country: Canada
state: British Columbia
city: Ottawa
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Pula
country: Croatia
city: Heidelberg
country: Germany
city: Kiel
country: Germany
city: Regensburg
country: Germany
city: Trier
country: Germany
city: Troisdorf
country: Germany
city: Ulm
country: Germany
city: Heraklion
country: Greece
city: Thessaloniki
country: Greece
city: Roma
country: Italy
state: Lazio
city: Monza
country: Italy
state: Lombardia
city: S. Fermo della Battaglia (CO)
country: Italy
state: Lombardia
city: Daegu
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Mexico City
country: Mexico
city: Xalapa
country: Mexico
city: Auckland
country: New Zealand
city: Aveiro
country: Portugal
city: Lisboa
country: Portugal
city: Bucharest
country: Romania
city: Cluj Napoca
country: Romania
city: Iasi
country: Romania
city: Belgrade
country: Serbia
city: Belgrade
country: Serbia
city: Durban
country: South Africa
city: Durban
country: South Africa
city: Pretoria
country: South Africa
city: San Sebastian
country: Spain
state: Guipuzcoa
city: Barcelona
country: Spain
city: Cordoba
country: Spain
city: Madrid
country: Spain
city: Eskilstuna
country: Sweden
city: Stockholm
country: Sweden
city: Sundsvall
country: Sweden
city: Umea
country: Sweden
city: Baden
country: Switzerland
city: Zürich
country: Switzerland
city: Zürich
country: Switzerland
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Bournemouth
country: United Kingdom
city: Derby
country: United Kingdom
city: Guildford
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Southampton
country: United Kingdom
city: Truro
country: United Kingdom
city: Westcliffe-on-sea
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, Eng-Wong J, Kirk S, Cortes J. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018 Jan;89:27-35. doi: 10.1016/j.ejca.2017.10.021. Epub 2017 Dec 8.
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: Schneeweiss A, Chia S, Hegg R, Tausch C, Deb R, Ratnayake J, McNally V, Ross G, Kiermaier A, Cortes J. Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab- and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study. Breast Cancer Res. 2014 Jul 8;16(4):R73. doi: 10.1186/bcr3690.
citation: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortes J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. doi: 10.1093/annonc/mdt182. Epub 2013 May 22.