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

NCT ID: NCT00976989

Last Updated: 2017-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 225 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2016-01-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pertuzumab

Intervention Type: DRUG

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

Trastuzumab

Intervention Type: DRUG

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

FEC

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Pertuzumab

Intervention Type: DRUG

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

Trastuzumab

Intervention Type: DRUG

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

FEC

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Pertuzumab

Intervention Type: DRUG

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

TCH

Intervention Type: 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.

Interventions

Pertuzumab

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

Intervention Type: DRUG

Trastuzumab

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

Intervention Type: DRUG

FEC

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

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

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 Type: DRUG

Other Intervention Names

Perjeta; Herceptin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Banja Luka, , Bosnia and Herzegovina

Sarajevo, , Bosnia and Herzegovina

Porto Alegre, Rio Grande do Sul, Brazil

São Paulo, São Paulo, Brazil

Vancouver, British Columbia, Canada

Ottawa, Ontario, Canada

Montreal, Quebec, Canada

Pula, , Croatia

Heidelberg, , Germany

Kiel, , Germany

Regensburg, , Germany

Trier, , Germany

Troisdorf, , Germany

Ulm, , Germany

Heraklion, , Greece

Thessaloniki, , Greece

Rome, Lazio, Italy

Monza, Lombardy, Italy

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

Mexico City, , Mexico

Xalapa, , Mexico

Auckland, , New Zealand

Aveiro, , Portugal

Lisbon, , Portugal

Bucharest, , Romania

Cluj-Napoca, , Romania

Iași, , Romania

Belgrade, , Serbia

Belgrade, , Serbia

Durban, , South Africa

Durban, , South Africa

Pretoria, , South Africa

Daegu, , South Korea

Seoul, , South Korea

Barcelona, Barcelona, Spain

Córdoba, Cordoba, Spain

Donostia / San Sebastian, Guipuzcoa, Spain

Madrid, Madrid, Spain

Eskilstuna, , Sweden

Stockholm, , Sweden

Sundsvall, , Sweden

Umeå, , Sweden

Baden, , Switzerland

Zurich, , Switzerland

Zurich, , Switzerland

Taichung, , Taiwan

Taipei, , Taiwan

Nassau, , The Bahamas

Bournemouth, , United Kingdom

Derby, , United Kingdom

Guildford, , United Kingdom

Newcastle upon Tyne, , United Kingdom

Southampton, , United Kingdom

Truro, , United Kingdom

Westcliffe-on-sea, , United Kingdom

Countries

Bosnia and Herzegovina; Brazil; Canada; Croatia; Germany; Greece; Italy; Mexico; New Zealand; Portugal; Romania; Serbia; South Africa; South Korea; Spain; Sweden; Switzerland; Taiwan; The Bahamas; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 29223479 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28057664 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25005255 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23704196 (View on PubMed)

Other Identifiers

2009-012019-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO22280

Identifier Type: -

Identifier Source: org_study_id