A Study of Pertuzumab in Combination With Herceptin and Chemotherapy in Participants With HER2-Positive Breast Cancer

NCT00976989 | Completed Phase 2 Results

• 2 other identifiers: BO222802009-012019-17
• Study Type: interventional
• Target: 225
• Locations: 19 countries
• Sites: 51

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  From baseline up to approximately 3.5 years

• 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.

  From baseline up to approximately 18 weeks

Secondary Outcomes (10)

• Efficacy: Percentage of Participants With Complete Pathological Response (pCR)

  At surgery, after 18 weeks (6 cycles) of treatment

• Efficacy: Clinical Response Rate

  During each 3-week cycle of 6 total cycles: up to 18 weeks

• Efficacy: Time to Clinical Response

  Up to 18 weeks

• Efficacy: Percentage of Participants Achieving Breast Conserving Surgery

  At approximately 18 weeks

• Efficacy: Percentage of Participants Without an Overall Survival (OS) Event

  From baseline to end of study up to 5 years

Study Arms (3)

T+P Concomitant Anthracycline-based chemotherapy

EXPERIMENTAL

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.

Drug: Pertuzumab; Drug: Trastuzumab; Drug: FEC; Drug: Docetaxel

T+P Sequential Anthracycline-based chemotherapy

EXPERIMENTAL

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.

Drug: Pertuzumab; Drug: Trastuzumab; Drug: FEC; Drug: Docetaxel

T+P Concomitant Non-Anthracycline chemotherapy

EXPERIMENTAL

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.

Drug: Pertuzumab; Drug: TCH

Interventions

Pertuzumab DRUG

840 mg loading dose intravenously (IV), then 420 mg IV 3-weekly.

Also known as: Perjeta

T+P Concomitant Anthracycline-based chemotherapy; T+P Concomitant Non-Anthracycline chemotherapy; T+P Sequential Anthracycline-based chemotherapy

Trastuzumab DRUG

8 mg/kg loading dose IV, then 6 mg/kg every 3 weeks.

Also known as: Herceptin

T+P Concomitant Anthracycline-based chemotherapy; T+P Sequential Anthracycline-based chemotherapy

FEC DRUG

5-fluorouracil 500 mg/m\^2, epirubicin 100 mg/m\^2 and cyclophosphamide 600 mg/m\^2.

T+P Concomitant Anthracycline-based chemotherapy; T+P Sequential Anthracycline-based chemotherapy

Docetaxel DRUG

75 mg/m\^2 for the first dose; 100 mg/m\^2 if no dose limiting toxicity occurs.

T+P Concomitant Anthracycline-based chemotherapy; T+P Sequential Anthracycline-based chemotherapy

TCH DRUG

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.

T+P Concomitant Non-Anthracycline chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (55)

Unknown Facility

Banja Luka, 78000, Bosnia and Herzegovina

Location

Unknown Facility

Sarajevo, 71000, Bosnia and Herzegovina

Location

Unknown Facility

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Unknown Facility

São Paulo, São Paulo, 01317-000, Brazil

Location

Unknown Facility

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Unknown Facility

Ottawa, Ontario, K1H 8L6, Canada

Location

Unknown Facility

Montreal, Quebec, H3G 1A4, Canada

Location

Unknown Facility

Pula, 52100, Croatia

Location

Unknown Facility

Heidelberg, 69120, Germany

Location

Unknown Facility

Kiel, 24105, Germany

Location

Unknown Facility

Regensburg, 93053, Germany

Location

Unknown Facility

Trier, 54290, Germany

Location

Unknown Facility

Troisdorf, 53840, Germany

Location

Unknown Facility

Ulm, 89075, Germany

Location

Unknown Facility

Heraklion, 71110, Greece

Location

Unknown Facility

Thessaloniki, 56429, Greece

Location

Unknown Facility

Rome, Lazio, 00168, Italy

Location

Unknown Facility

Monza, Lombardy, 20900, Italy

Location

Unknown Facility

S. Fermo Della Battaglia (CO), Lombardy, 22020, Italy

Location

Unknown Facility

Mexico City, 06760, Mexico

Location

Unknown Facility

Xalapa, 91130, Mexico

Location

Unknown Facility

Auckland, 1023, New Zealand

Location

Unknown Facility

Aveiro, 3814-501, Portugal

Location

Unknown Facility

Lisbon, 1099-023, Portugal

Location

Unknown Facility

Bucharest, 050098, Romania

Location

Unknown Facility

Cluj-Napoca, 400015, Romania

Location

Unknown Facility

Iași, 700106, Romania

Location

Unknown Facility

Belgrade, 11000, Serbia

Location

Unknown Facility

Belgrade, 11080, Serbia

Location

Unknown Facility

Durban, 4058, South Africa

Location

Unknown Facility

Durban, 4091, South Africa

Location

Unknown Facility

Pretoria, 0002, South Africa

Location

Unknown Facility

Daegu, 702-210, South Korea

Location

Unknown Facility

Seoul, 152-703, South Korea

Location

Unknown Facility

Barcelona, Barcelona, 08035, Spain

Location

Unknown Facility

Córdoba, Cordoba, 14004, Spain

Location

Unknown Facility

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Unknown Facility

Madrid, Madrid, 28222, Spain

Location

Unknown Facility

Eskilstuna, 63188, Sweden

Location

Unknown Facility

Stockholm, 17176, Sweden

Location

Unknown Facility

Sundsvall, 85186, Sweden

Location

Unknown Facility

Umeå, 90185, Sweden

Location

Unknown Facility

Baden, 5405, Switzerland

Location

Unknown Facility

Zurich, 8008, Switzerland

Location

Unknown Facility

Zurich, 8091, Switzerland

Location

Unknown Facility

Taichung, 404, Taiwan

Location

Unknown Facility

Taipei, 00112, Taiwan

Location

Unknown Facility

Nassau, N9311, The Bahamas

Location

Unknown Facility

Bournemouth, BH7 7DW, United Kingdom

Location

Unknown Facility

Derby, DE1 2QY, United Kingdom

Location

Unknown Facility

Guildford, GU2 5XX, United Kingdom

Location

Unknown Facility

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Unknown Facility

Southampton, SO16 6YD, United Kingdom

Location

Unknown Facility

Truro, TR1 3LJ, United Kingdom

Location

Unknown Facility

Westcliffe-on-sea, SS0 0RY, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 29223479 DERIVED

• 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.

  PMID: 28057664 DERIVED

• 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.

  PMID: 25005255 DERIVED

• 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.

  PMID: 23704196 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumab; Trastuzumab; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2009
• First Posted: September 15, 2009
• Study Start: November 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: January 1, 2016
• Last Updated: February 6, 2017
• Results First Posted: June 20, 2016

Record last verified: 2016-05

Locations

SE (2); IT (3); GR (2); ME (2); BO (2); DE (6); ZA (3); BR (2); ES (4); TH (1); CH (3); TW (2); CA (3); RO (3); GB (7); NZ (1); CR (1); KR (2); PT (2)