Trastuzumab & Pertuzumab Followed by T-DM1 in MBC

NCT01835236 | Completed Phase 2 DMC

• 3 other identifiers: SAKK 22/102012-002556-17UNICANCER UC-0140/1207
• Study Type: interventional
• Target: 208
• Locations: 4 countries
• Sites: 71

Brief Summary

In HER2-positive metastatic breast cancer, trastuzumab based treatment is the standard of care as long as there are no contraindications to trastuzumab. Frequently, trastuzumab is being combined with taxanes in the first-line setting. However, since therapy with trastuzumab is active even in the absence of chemotherapy in HER2-positive MBC, the optimal treatment strategy either in combination or in sequence with chemotherapy is still under debate. This randomized phase II trial is studying a new strategy for the treatment of metastatic breast cancer with HER2-positive. First-line treatment consists of trastuzumab and pertuzumab, a treatment without chemotherapy. In case of disease progression, chemotherapy with T-DM1 is then performed as second-line treatment. Third-line and further line therapies are performed according to the physician's discretion. If this new therapeutic strategy is as effective and better tolerated than the conventional strategy, this would mean a serious breakthrough in the treatment of HER2-positive metastatic breast cancer.

Conditions

Metastatic Breast Cancer

Keywords

Breast cancer; HER2-positive; Metastases

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS) - Analysis Population: ITT Population 1

  Patients being alive 24 months after randomization. A success is considered if a patient is alive at least 24 months after randomization. Analysis Population: ITT Population 1

  24 months

Secondary Outcomes (15)

• OS - Analysis Population: ITT Population 2

  24 months

• Progression Free Survival (PFS) of first-line treatment ignoring first Central Nervous System (CNS) lesion

  10 / 16 months (PFS will be calculated sustained from randomization until documented PD (ignoring first CNS lesion) or death, whichever occurs first during first-line treatment )

• PFS of second-line treatment

  8 months (PFS will be calculated sustained from registration of second line treatment until documented PD, PD CNS or death, whichever occurs first during second-line treatment)

• PFS of second-line treatment ignoring first CNS lesion

  9 months (PFS will be calculated sustained from registration of second line treatment until documented PD (ignoring first CNS lesion) or death, whichever occurs first during second-line treatment)

• Time to failure of strategy (TFS) of first- plus second-line treatment

  18 / 24 months (TFS will be calculated sustained from randomization until documented PD, PD CNS or death, whichever occurs first before starting third-line therapy )

Study Arms (2)

Trastuzumab, Pertuzumab, T-DM1

ACTIVE COMPARATOR

First line therapy: Trastuzumab, Pertuzumab Second line therapy: T-DM1

Drug: Trastuzumab; Drug: Pertuzumab; Drug: T-DM1

Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1

ACTIVE COMPARATOR

First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Paclitaxel; Drug: Vinorelbine; Drug: T-DM1

Interventions

Trastuzumab DRUG

First administration (loading dose) 8 mg/kg i.v. infusion over 90 min. \- then every 3 weeks until progression 6 mg/kg i.v. infusion over 30 to 90 min.

Also known as: Herceptin

Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1; Trastuzumab, Pertuzumab, T-DM1

Pertuzumab DRUG

First administration (loading dose) 840 mg i.v. infusion over 60 min. \- then every 3 weeks until progression 420 mg i.v. infusion over 30 to 60 min.

Also known as: Perjeta

Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1; Trastuzumab, Pertuzumab, T-DM1

Paclitaxel DRUG

Day 1, 8 and 15; every 4 weeks for ≥4 months 90 mg/m2 i.v. infusion

Also known as: Taxol

Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1

Vinorelbine DRUG

First administration: Day 1 and 8 25 mg/m2 i.v. infusion * then day 1 and 8, every 3 weeks for ≥4 months 30 mg/m2 i.v. infusion

Also known as: Navelbine

Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1

T-DM1 DRUG

Every 3 weeks until unacceptable toxicity or progressive disease is observed 3.6 mg/kg i.v. infusion First dose: over 90 min (± 10 min.) Subsequent doses: over 30 min. (± 10 min.)

Also known as: Trastuzumab emtansine

Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1; Trastuzumab, Pertuzumab, T-DM1

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed breast cancer with distant metastases
• Note:
• A biopsy from the primary tumor or a metastasis can be used for diagnosis.
• Patients with non-measurable lesions are eligible.
• Patients with inoperable, locally advanced breast cancer with lymph node metastases other than ipsilateral locoregional (axillary, infraclavicular, parasternal) or other distant metastases are eligible.
• Patients with bone metastases with or without bone targeted therapy (bisphosphonates, denosumab) are eligible.
• Patients with de-novo Stage IV disease are eligible.
• HER2-positive tumor according to central pathology testing for HER2
• Note:
• A formalin-fixed paraffin-embedded (FFPE) biopsy from the primary tumor or a metastasis has to be used for HER2 status determination. If a biopsy is available from a metastasis, the HER2 testing should be performed using the metastasis.
• Fine needle aspiration is not acceptable for HER 2 testing. • Women aged ≥18 years
• WHO performance status 0 to 2
• Left Ventricular Ejection Fraction (LVEF) ≥50% as determined by either ECHO or MUGA
• Adequate organ function, evidenced by the following laboratory results:
• Neutrophils \>1.5x109/L, platelets \>100x109/L, hemoglobin ≥90g/L, total bilirubin ≤1.5xULN (unless the patients has documented Gilbert's disease), AST ≤3xULN, ALT ≤3xULN, AP ≤2.5xULN (except in patients with bone metastases: AP ≤5xULN), creatinine ≤1.5xULN

You may not qualify if:

• Prior chemotherapy for inoperable locally advanced or metastatic breast cancer
• Note:
• Prior neoadjuvant/adjuvant chemotherapy is allowed if doses for anthracyclines have not exceeded 720mg/m2 and 240mg/m2 for epirubicin and doxorubicin, respectively.
• \- Re-exposure to paclitaxel is permitted, if the last dose of taxane was given at least 1 year before randomization.
• \- Re-exposure to vinorelbine is permitted, if the last dose of vinorelbine was given at least 1 year before randomization.
• Prior anti-HER2 treatment for metastatic or inoperable breast cancer
• Note:
• Prior neoadjuvant/adjuvant anti-HER2 treatment with trastuzumab and/or lapatinib is allowed.
• More than one endocrine treatment line for metastatic or inoperable breast cancer exceeding a duration of 1 month
• Note:
• <!-- -->
• Adjuvant endocrine treatment is not counted as one line.
• Patients progressing on endocrine treatment: this specific endocrine treatment must have been stopped at least 2 weeks prior to randomization.
• Prior treatment with pertuzumab and/or T-DM1
• Known leptomeningeal or CNS metastases

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (71)

Hopital Sud - Amiens

Amiens, 80054, France

Location

ICO - Paul Papin

Angers, 49933, France

Location

Institut Sainte Catherine

Avignon, 84918, France

Location

Centre Hospitalier de Blois

Blois, 41016, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Hôpital Morvan (Brest)

Brest, 29200, France

Location

Centre Francois Baclesse

Caen, 14076, France

Location

Centre Hospitalier Alpes Leman

Contamine-sur-Arve, 74130, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Centre Hospitalier de Dracenie

Draguignan, 83007, France

Location

Hopital Michallon - Centre Hospitalier Universitaire de Grenoble

Grenoble, 38043, France

Location

Clinique Hartmann

Levallois-Perret, 92300, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Chu de Limoges - Hopital Dupuytren

Limoges, 87042, France

Location

Centre Hospitalier - Site Hopital du Scorff

Lorient, 56322, France

Location

Clinique de la Sauvegarde

Lyon, 69009, France

Location

Fondation Hopital Ambroise Pare - Hopital Europeen

Marseille, 13003, France

Location

Istitut Paoli Calmettes

Marseille, 13273, France

Location

Institut Regional du Cancer Montpellier Val d'Aurelle

Montpellier, 34298, France

Location

Centre Azureen de Cancerologie

Mougins, 6250, France

Location

Polyclinique de Gentilly

Nancy, 54100, France

Location

Centre Catherine de Sienne

Nantes, 44202, France

Location

Centre Antoine Lacassagne

Nice, 6189, France

Location

Hopital Saint Louis

Paris, 75475, France

Location

Centre Hospitalier de Pau

Pau, 64046, France

Location

Centre Hospitalier de Perpignan - Hopital Saint Jean

Perpignan, 66046, France

Location

Institut Jean Godinot

Reims, 51726, France

Location

Clinique Mathilde

Rouen, 76000, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Curie Site Saint-Cloud

Saint-Cloud, 92210, France

Location

ICO - Rene Gauducheau

Saint-Herblain, 44805, France

Location

Institut de Cancerologie de la Loire

Saint-Priest-en-Jarez, 42271, France

Location

Hopitaux Universitaire de Strasbourg - Hopital Civil

Strasbourg, 67091, France

Location

Hopitaux du Leman - Site Georges Pianta

Thonon-les-Bains, 74203, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Centre Hospitalier de Valence

Valence, 26953, France

Location

Universitäts-Frauenklinik Ulm

Ulm, 89075, Germany

Location

Almelo_Ziekenhuisgroep Twente

Almelo, 7609 PP, Netherlands

Location

VUmc University Medical Center

Amsterdam, 1007, Netherlands

Location

Antoni van Leeuwenhoek / Slotervaart hospital

Amsterdam, 1066 CX, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, 2625 AD, Netherlands

Location

Deventer Ziekenhuis

Deventer, 7416 SE, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, 5623 EJ, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, 8934 AD, Netherlands

Location

Leiden_Leids Universitair Medisch Centrum (LUMC)

Leiden, 2333 ZA, Netherlands

Location

St. Antonius Ziekenhuis, Ioc Nieuwegein

Nieuwegein, 3430 EM, Netherlands

Location

St. Franciscus Gasthuis Rotterdam

Rotterdam, 3045 PM, Netherlands

Location

Vlietland Ziekenhuis

Schiedam, 3118 JH, Netherlands

Location

Orbis Medisch Centrum

Sittard, 6162 BG, Netherlands

Location

Haga Ziekenhuis

The Hague, 2545 CH, Netherlands

Location

Hirslanden Klinik Aarau

Aarau, CH-5001, Switzerland

Location

Kantonspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Universitaetsspital-Basel

Basel, 4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital, Bern

Bern, CH-3010, Switzerland

Location

RSV-GNW Spitalzentrum Oberwallis

Brig, 3900, Switzerland

Location

Spitalzentrum Oberwallis

Brig, 3900, Switzerland

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

Kantonsspital Frauenfeld / Brustzentrum Thurgau

Frauenfeld, 8501, Switzerland

Location

Hopitaux Universitaires de Geneve

Geneva, 1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois CHUV

Lausanne, CH-1011, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Liestal

Liestal, CH-4410, Switzerland

Location

Kantonsspital Luzern

Luzerne, CH-6000, Switzerland

Location

Kantonsspital Olten

Olten, 4600, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Zentrum fuer Tumordiagnostik und Praevention

Sankt Gallen, CH-9006, Switzerland

Location

SpitalSTS AG Simmental-Thun-Saanenland

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Universitäts Spital Zürich

Zurich, 8091, Switzerland

Location

Related Publications (1)

• Huober J, Weder P, Ribi K, Thurlimann B, Thery JC, Li Q, Vanlemmens L, Guiu S, Brain E, Grenier J, Dalenc F, Levy C, Savoye AM, Muller A, Membrez-Antonioli V, Gerard MA, Lemonnier J, Hawle H, Dietrich D, Boven E, Bonnefoi H; Swiss Group for Clinical Cancer Research, Unicancer Breast Group, and Dutch Breast Cancer Research Group. Pertuzumab Plus Trastuzumab With or Without Chemotherapy Followed by Emtansine in ERBB2-Positive Metastatic Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2023 Oct 1;9(10):1381-1389. doi: 10.1001/jamaoncol.2023.2909.

  PMID: 37561451 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Trastuzumab; pertuzumab; Paclitaxel; Vinorelbine; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Maytansine; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Jens Huober, MD

  University of Ulm

  STUDY CHAIR

• Patrik Weder, MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

• Hervé Bonnefoi, Prof

  Institut Bergonié Bordeaux

  STUDY CHAIR

• Epie Boven, MD

  Amsterdam UMC, location VUmc

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: April 15, 2013
• First Posted: April 18, 2013
• Study Start: March 3, 2013
• Primary Completion: January 11, 2018
• Study Completion: May 26, 2020
• Last Updated: March 30, 2021

Record last verified: 2021-03

Locations

FR (36); DE (1); NL (13); CH (21)