Trastuzumab & Pertuzumab Followed by T-DM1 in MBC
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT01835236
- Lead Sponsor
- Swiss Group for Clinical Cancer Research
- 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.
- Detailed Description
OBJECTIVES:
Primary
-To evaluate the efficacy in terms of overall survival (OS) at 24 months of a chemotherapy-free dual HER2-inhibition with trastuzumab and pertuzumab (first-line) followed by T-DM1 (second-line) and of a chemotherapy-containing dual HER2-inhibition with trastuzumab and pertuzumab (first-line) followed by T-DM1 (second-line) in patients with HER2-positive metastatic breast cancer.
Secondary
* To evaluate other efficacy parameter
* To evaluate the safety and tolerability profile of the two treatment strategies
* To evaluate the Quality of Life (QoL)
* To learn how patients are treated after trial treatment
OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor status (positive vs negative), prior trastuzumab (never or \>12 months vs ≤12 months after last infusion), visceral metastases (present vs absent) and site. Patients are randomized to 1 of 2 treatment arms.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 208
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Trastuzumab, Pertuzumab, T-DM1 Pertuzumab First line therapy: Trastuzumab, Pertuzumab Second line therapy: T-DM1 Trastuzumab, Pertuzumab, T-DM1 Trastuzumab First line therapy: Trastuzumab, Pertuzumab Second line therapy: T-DM1 Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1 Trastuzumab First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1 Trastuzumab, Pertuzumab, T-DM1 T-DM1 First line therapy: Trastuzumab, Pertuzumab Second line therapy: T-DM1 Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1 Pertuzumab First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1 Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1 T-DM1 First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1 Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1 Paclitaxel First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1 Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1 Vinorelbine First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1
- Primary Outcome Measures
Name Time Method Overall survival (OS) - Analysis Population: ITT Population 1 24 months 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
- Secondary Outcome Measures
Name Time Method OS - Analysis Population: ITT Population 2 24 months Proportion of 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 2
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 first-line treatment ignoring first CNS lesion is the time from randomization to first event progression. A PFS of first-line treatment ignoring first CNS lesion event is defined as (whichever occurs first):
* Disease progression (PD) after having received first-line treatment and prior to the next treatment
* Death due to any reason Patients without events will be censored at last tumor assessment date without PFS ignoring first CNS lesion event during the first-line treatment period or prior to starting new treatment.
Analysis population: ITT Population 1PFS 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) PFS of second-line treatment ignoring first CNS lesion is the time from registration of second-line treatment to the first event occurs. A PFS of second-line treatment ignoring first CNS lesion event is defined as (whichever occurs first):
* Disease progression after having received second-line treatment and prior to the next treatment
* Death due any reason during the second-line treatment period Patients without events will be censored at last tumor assessment date without PFS ignoring first CNS lesion event during the second-line treatment period or prior to starting new treatment.
Analysis Population: ITT Population 2DC of second-line treatment (based on investigator assessment) 6 months (DC is defined as the response CR, PR or SD for 6 months after registration of second-line treatment) AEs grade ≥2 until first progression (ignoring first CNS lesion) Throughout first-line treatment (estimated up to 16 months) Adverse events are assessed by Common terminology criteria for adverse events (CTCAE) v4.0. From randomization until first progression (documented PD, PD CNS or death)
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 is the time from registration of second-line treatment to progression. A PFS event of second-line treatment is defined as (whichever occurs first):
* Disease progression after having received second-line treatment and prior to the next treatment
* PD CNS after having received first-line treatment and prior to the next treatment
* Death due any reason during the second-line treatment period Patients without events will be censored at last tumor assessment date without PD and PD CNS during the second-line treatment period or prior to starting new treatment.
Analysis Population: ITT Population 2Time 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 ) TFS of first plus second-line treatment is the time from randomization to TFS event occurs. A TFS event of first plus second-line treatment is defined as (whichever occurs first):
* Disease progression after having received the first and second-line treatment and prior to the next treatment
* PD CNS after having received first- and second-line treatment and prior to the next treatment
* Death due to tumor prior to the third-line treatment Patients without events will be censored at last tumor assessment without PD and PD CNS during first and second-line treatment period or prior to starting new treatment.
Analysis Population: ITT Population 1OR of second-line treatment (based on investigator assessment) 9 months (OR is defined as the best status of response CR or PR after registration for second-line treatment up to second progression or start of a new treatment) Adverse events (AEs) according to the NCI CTCAE v4.0 of first-line treatment Throughout first-line treatment (estimated up to 16 months) Adverse events are assessed by the NCI CTCAE v4.0. from registration until registration of second-line treatment or start of follow-up (which occurs first).
Overall survival OS OS will be calculated from randomization until death (estimated median: 32 months) OS will be calculated from randomization until death. Patients still alive or lost of follow up are censored at their last date known alive.
Analysis Population: ITT Population 1Objective response (OR) of first-line treatment (based on investigator assessment) 10 / 16 months (OR is defined as the best status of response CR or PR up to first progression or start of a new treatment) Disease control (DC) of first-line treatment (based on investigator assessment) 6 months (DC is defined as CR, PR or SD for 6 months after randomization and no PD at 6 month after randomization) AEs according to the NCI CTCAE v4.0 of second-line treatment Throughout second-line treatment (estimated up to 9 months) Adverse events are assessed by the NCI CTCAE v4.0.from second-line registration until PD or start of follow-up (which occurs first) plus 30 days.
Quality of Life (QoL) At baseline and every 12 weeks (three-monthly) until progression or up to a maximum of 24 months during 1st line therapy. Within 3 weeks prior to registration, after 12 and 24 weeks during 2nd line therapy. PFS of third-line treatment 4 months PFS will be calculated sustained from start of third-line treatment to progression (PD, PD CNS or death)
Trial Locations
- Locations (71)
Hirslanden Klinik Aarau
🇨🇭Aarau, Switzerland
Kantonspital Aarau
🇨🇭Aarau, Switzerland
Kantonsspital Baden
🇨🇭Baden, Switzerland
Spitalzentrum Oberwallis
🇨🇭Brig, Switzerland
Kantonsspital Luzern
🇨🇭Luzerne, Switzerland
Kantonsspital Olten
🇨🇭Olten, Switzerland
Universitaetsspital-Basel
🇨🇭Basel, Switzerland
Inselspital, Bern
🇨🇭Bern, Switzerland
Kantonsspital Liestal
🇨🇭Liestal, Switzerland
Kantonsspital Frauenfeld / Brustzentrum Thurgau
🇨🇭Frauenfeld, Switzerland
Hopitaux Universitaires de Geneve
🇨🇭Genève 14, Switzerland
Centre Hospitalier Universitaire Vaudois CHUV
🇨🇭Lausanne, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
SpitalSTS AG Simmental-Thun-Saanenland
🇨🇭Thun, Switzerland
Kantonsspital Winterthur
🇨🇭Winterthur, Switzerland
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland
Hôpital Morvan (Brest)
🇫🇷Brest, France
Clinique de la Sauvegarde
🇫🇷Lyon, France
Centre Hospitalier Alpes Leman
🇫🇷Contamine-Sur-Arve, France
Centre Hospitalier - Site Hopital du Scorff
🇫🇷Lorient Cedex, France
ICO - Paul Papin
🇫🇷Angers, France
Clinique Hartmann
🇫🇷Levallois-Perret, France
VUmc University Medical Center
🇳🇱Amsterdam, Netherlands
Institut Claudius Regaud
🇫🇷Toulouse Cedex 9, France
Centre Antoine Lacassagne
🇫🇷Nice Cedex 2, France
Chu de Limoges - Hopital Dupuytren
🇫🇷Limoges, France
Istitut Paoli Calmettes
🇫🇷Marseille, France
Polyclinique de Gentilly
🇫🇷Nancy, France
Medisch Centrum Leeuwarden
🇳🇱Leeuwarden, Netherlands
Orbis Medisch Centrum
🇳🇱Sittard, Netherlands
Centre Hospitalier de Blois
🇫🇷Blois, France
Institut Bergonie
🇫🇷Bordeaux, France
Vlietland Ziekenhuis
🇳🇱Schiedam, Netherlands
Almelo_Ziekenhuisgroep Twente
🇳🇱Almelo, Netherlands
Haga Ziekenhuis
🇳🇱Den Haag, Netherlands
Leiden_Leids Universitair Medisch Centrum (LUMC)
🇳🇱Leiden, Netherlands
Hopital Sud - Amiens
🇫🇷Amiens, France
Centre Georges François Leclerc
🇫🇷Dijon Cedex, France
Centre Hospitalier de Dracenie
🇫🇷Draguignan, France
Institut Regional du Cancer Montpellier Val d'Aurelle
🇫🇷Montpellier, France
Centre Azureen de Cancerologie
🇫🇷Mougins, France
Antoni van Leeuwenhoek / Slotervaart hospital
🇳🇱Amsterdam, Netherlands
Universitäts-Frauenklinik Ulm
🇩🇪Ulm, Germany
Reinier de Graaf Gasthuis
🇳🇱Delft, Netherlands
St. Franciscus Gasthuis Rotterdam
🇳🇱Rotterdam, Netherlands
Clinique Mathilde
🇫🇷Rouen, France
Centre Henri Becquerel
🇫🇷Rouen, France
Curie Site Saint-Cloud
🇫🇷Saint-Cloud, France
Hopitaux Universitaire de Strasbourg - Hopital Civil
🇫🇷Strasbourg, France
Hopitaux du Leman - Site Georges Pianta
🇫🇷Thonon Les Bains, France
St. Antonius Ziekenhuis, Ioc Nieuwegein
🇳🇱Nieuwegein, Netherlands
Centre Francois Baclesse
🇫🇷Caen, France
Institut Jean Godinot
🇫🇷Reims, France
ICO - Rene Gauducheau
🇫🇷Saint Herblain, France
Centre Hospitalier de Valence
🇫🇷Valence Cedex 9, France
Institut Sainte Catherine
🇫🇷Avignon Cedex 9, France
Centre Oscar Lambret
🇫🇷Lille, France
Hopital Michallon - Centre Hospitalier Universitaire de Grenoble
🇫🇷Grenoble, France
Fondation Hopital Ambroise Pare - Hopital Europeen
🇫🇷Marseille, France
Centre Catherine de Sienne
🇫🇷Nantes, France
Hopital Saint Louis
🇫🇷Paris, France
Institut de Cancerologie de la Loire
🇫🇷Saint-Priest-En-Jarez, France
Centre Hospitalier de Pau
🇫🇷Pau, France
Centre Hospitalier de Perpignan - Hopital Saint Jean
🇫🇷Perpignan, France
Catharina Ziekenhuis
🇳🇱Eindhoven, Netherlands
Deventer Ziekenhuis
🇳🇱Deventer, Netherlands
RSV-GNW Spitalzentrum Oberwallis
🇨🇭Brig, Switzerland
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
🇨🇭Bellinzona, Switzerland
Kantonsspital Graubuenden
🇨🇭Chur, Switzerland
Zentrum fuer Tumordiagnostik und Praevention
🇨🇭St. Gallen, Switzerland
Universitäts Spital Zürich
🇨🇭Zürich, Switzerland