Metastatic Breast CancerPhase 2NCT01835236
Trastuzumab & Pertuzumab Followed by T-DM1 in MBC
A Phase 2 study testing Trastuzumab, Pertuzumab and Paclitaxel in people with Metastatic Breast Cancer, run by Swiss Cancer Institute at 71 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Trastuzumab, Pertuzumab and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 208 participants
- Where
- 71 sitesin 4 countries
- Study dates
- 3 Mar 2013to 26 May 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
- Note:
- A brain MRI or CT scan is mandatory in case of clinical suspicion of CNS metastases.
- Single bone metastasis treated with radiotherapy (if the bone metastasis is the only tumor lesion)
- Inclusion criteria for second-line therapy • At least one dose of trial therapy in the first-line treatment phase of this trial
- • Proven disease progression on first-line therapy or radiotherapy of a bone metastasis
- Notes:
- First new parenchymal CNS metastases only do not count as progression requiring the initiation of second line trial treatment. Radiotherapy of a single area only for pain control is allowed and will not count as PD.
- 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, AP ≤2.5xULN (except in patients with bone metastases: AP ≤5xULN), creatinine ≤1.5ULN
- LVEF ≥50% as determined by either ECHO or MUGA
- QoL questionnaire has been completed.
- Termination of first-line therapy with trastuzumab/pertuzumab due to unacceptable toxicity without objective evidence of disease progression
- CNS metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as a history of radiation, surgery, or other therapy, including steroids, to control symptoms from CNS metastases within 2 months (60 days) before registration
- Peripheral neuropathy of CTCAE grade ≥3
- Interstitial lung disease (ILD) or pneumonitis grade ≥3
- Any other adverse event which has not recovered to CTCAE grade ≤1 (except alopecia)
Trial locations and contacts
71 sites in 4 countries.
71 sites in 4 countries
France36 sites
Hopital Sud - Amiens
Amiens, 80054
ICO - Paul Papin
Angers, 49933
Institut Sainte Catherine
Avignon, 84918
Centre Hospitalier de Blois
Blois, 41016
Institut Bergonie
Bordeaux, 33076
Hôpital Morvan (Brest)
Brest, 29200
Centre Francois Baclesse
Caen, 14076
Centre Hospitalier Alpes Leman
Contamine-sur-Arve, 74130
Centre Georges François Leclerc
Dijon, 21079
Centre Hospitalier de Dracenie
Draguignan, 83007
Hopital Michallon - Centre Hospitalier Universitaire de Grenoble
Grenoble, 38043
Clinique Hartmann
Levallois-Perret, 92300
Centre Oscar Lambret
Lille, 59020
Chu de Limoges - Hopital Dupuytren
Limoges, 87042
Centre Hospitalier - Site Hopital du Scorff
Lorient, 56322
Clinique de la Sauvegarde
Lyon, 69009
Fondation Hopital Ambroise Pare - Hopital Europeen
Marseille, 13003
Istitut Paoli Calmettes
Marseille, 13273
Institut Regional du Cancer Montpellier Val d'Aurelle
Montpellier, 34298
Centre Azureen de Cancerologie
Mougins, 6250
Polyclinique de Gentilly
Nancy, 54100
Centre Catherine de Sienne
Nantes, 44202
Centre Antoine Lacassagne
Nice, 6189
Hopital Saint Louis
Paris, 75475
Centre Hospitalier de Pau
Pau, 64046
Centre Hospitalier de Perpignan - Hopital Saint Jean
Perpignan, 66046
Institut Jean Godinot
Reims, 51726
Clinique Mathilde
Rouen, 76000
Centre Henri Becquerel
Rouen, 76038
Curie Site Saint-Cloud
Saint-Cloud, 92210
ICO - Rene Gauducheau
Saint-Herblain, 44805
Institut de Cancerologie de la Loire
Saint-Priest-en-Jarez, 42271
Hopitaux Universitaire de Strasbourg - Hopital Civil
Strasbourg, 67091
Hopitaux du Leman - Site Georges Pianta
Thonon-les-Bains, 74203
Institut Claudius Regaud
Toulouse, 31059
Centre Hospitalier de Valence
Valence, 26953
Switzerland21 sites
Hirslanden Klinik Aarau
Aarau, CH-5001
Kantonspital Aarau
Aarau, CH-5001
Kantonsspital Baden
Baden, 5404
Universitaetsspital-Basel
Basel, 4031
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
Bellinzona, 6500
Inselspital, Bern
Bern, CH-3010
RSV-GNW Spitalzentrum Oberwallis
Brig, 3900
Spitalzentrum Oberwallis
Brig, 3900
Kantonsspital Graubuenden
Chur, 7000
Kantonsspital Frauenfeld / Brustzentrum Thurgau
Frauenfeld, 8501
Hopitaux Universitaires de Geneve
Geneva, 1211
Centre Hospitalier Universitaire Vaudois CHUV
Lausanne, CH-1011
Centre Hospitalier Universitaire Vaudois
Lausanne, CH-1011
Kantonsspital Liestal
Liestal, CH-4410
Kantonsspital Luzern
Luzerne, CH-6000
Kantonsspital Olten
Olten, 4600
Kantonsspital St. Gallen
Sankt Gallen, 9007
Zentrum fuer Tumordiagnostik und Praevention
Sankt Gallen, CH-9006
SpitalSTS AG Simmental-Thun-Saanenland
Thun, 3600
Kantonsspital Winterthur
Winterthur, 8401
Universitäts Spital Zürich
Zurich, 8091
Netherlands13 sites
Almelo_Ziekenhuisgroep Twente
Almelo, 7609 PP
VUmc University Medical Center
Amsterdam, 1007
Antoni van Leeuwenhoek / Slotervaart hospital
Amsterdam, 1066 CX
Reinier de Graaf Gasthuis
Delft, 2625 AD
Deventer Ziekenhuis
Deventer, 7416 SE
Catharina Ziekenhuis
Eindhoven, 5623 EJ
Medisch Centrum Leeuwarden
Leeuwarden, 8934 AD
Leiden_Leids Universitair Medisch Centrum (LUMC)
Leiden, 2333 ZA
St. Antonius Ziekenhuis, Ioc Nieuwegein
Nieuwegein, 3430 EM
St. Franciscus Gasthuis Rotterdam
Rotterdam, 3045 PM
Vlietland Ziekenhuis
Schiedam, 3118 JH
Orbis Medisch Centrum
Sittard, 6162 BG
Haga Ziekenhuis
The Hague, 2545 CH
About this study
Official title: A Randomized Phase II Trial of Pertuzumab in Combination With Trastuzumab With or Without Chemotherapy, Both Followed by T-DM1 in Case of Progression, in Patients With HER2-positive Metastatic Breast Cancer
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.
Read the 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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Trastuzumab, Pertuzumab, Paclitaxel, Vinorelbine, T-DM1
- Keywords
- Breast cancer, HER2-positive, Metastases
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called Herceptin
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.
PertuzumabDrug
Also called Perjeta
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.
PaclitaxelDrug
Also called Taxol
Day 1, 8 and 15; every 4 weeks for ≥4 months 90 mg/m2 i.v. infusion
VinorelbineDrug
Also called Navelbine
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
T-DM1Drug
Also called Trastuzumab emtansine
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.)
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab, Pertuzumab, T-DM1 | Active comparator | First line therapy: Trastuzumab, Pertuzumab Second line therapy: T-DM1 Receives: 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 Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Paclitaxel; Drug: Vinorelbine; Drug: T-DM1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 months
Secondary outcomes (15)
OS - Analysis Population: ITT Population 2
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
Measured: 24 months
Progression Free Survival (PFS) of first-line treatment ignoring first Central Nervous System (CNS) lesion
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 1
Measured: 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
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 2
Measured: 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
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 2
Measured: 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
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 1
Measured: 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 )
Overall survival OS
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 1
Measured: OS will be calculated from randomization until death (estimated median: 32 months)
Objective response (OR) of first-line treatment (based on investigator assessment)
Measured: 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)
Measured: 6 months (DC is defined as CR, PR or SD for 6 months after randomization and no PD at 6 month after randomization)
OR of second-line treatment (based on investigator assessment)
Measured: 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)
DC of second-line treatment (based on investigator assessment)
Measured: 6 months (DC is defined as the response CR, PR or SD for 6 months after registration of second-line treatment)
Adverse events (AEs) according to the NCI CTCAE v4.0 of first-line treatment
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).
Measured: Throughout first-line treatment (estimated up to 16 months)
AEs according to the NCI CTCAE v4.0 of second-line treatment
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.
Measured: Throughout second-line treatment (estimated up to 9 months)
AEs grade ≥2 until first progression (ignoring first CNS lesion)
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)
Measured: Throughout first-line treatment (estimated up to 16 months)
Quality of Life (QoL)
Measured: 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
PFS will be calculated sustained from start of third-line treatment to progression (PD, PD CNS or death)
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2013 (estimated)
- Study start3 Mar 2013
- Primary completion11 Jan 2018
- Study completion26 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 208 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swiss Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jens Huober, MD, Study chair, University of UlmPatrik Weder, MD, Study chair, Cantonal Hospital of St. GallenHervé Bonnefoi, Prof, Study chair, Institut Bergonié BordeauxEpie Boven, MD, Study chair, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01835236
- Sponsor's protocol ID
- SAKK 22/10
- Other IDs
- 2012-002556-17, UNICANCER UC-0140/1207
- Status last verified
- Mar 2021
- First submitted
- 15 Apr 2013
- Last updated
- 30 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 37561451
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Trial of Pertuzumab in Combination With Trastuzumab With or Without Chemotherapy, Both Followed by T-DM1 in Case of Progression, in Patients With HER2-positive Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT01835236
- Acronym / sponsor ID
- SAKK 22/10
- Conditions
- Metastatic Breast Cancer
- Keywords
- Breast cancer, HER2-positive, Metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 208 participants (actual)
- Lead sponsor
- Swiss Cancer InstituteUniversity, hospital or other
- Study start
- 3 Mar 2013 (actual)
- Primary completion
- 11 Jan 2018 (actual)
- Study completion
- 26 May 2020 (actual)
- First posted
- 18 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab, Pertuzumab, T-DM1 | Active comparator | Drug: Trastuzumab, Drug: Pertuzumab, Drug: T-DM1First line therapy: Trastuzumab, Pertuzumab Second line therapy: T-DM1 |
| Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1 | Active comparator | Drug: Trastuzumab, Drug: Pertuzumab, Drug: Paclitaxel, Drug: Vinorelbine, Drug: T-DM1First line therapy: Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine Second line therapy: T-DM1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically confirmed breast cancer with distant metastases
- 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.
Key exclusion criteria (30 listed)
- Prior neoadjuvant/adjuvant chemotherapy is allowed if doses for anthracyclines have not exceeded 720mg/m2 and 240mg/m2 for epirubicin and doxorubicin, respectively.
- Prior neoadjuvant/adjuvant anti-HER2 treatment with trastuzumab and/or lapatinib is allowed.
- <!-- -->
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrastuzumabAlso: HerceptinFirst 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. | Drug | Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1, Trastuzumab, Pertuzumab, T-DM1 |
| PertuzumabAlso: PerjetaFirst 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. | Drug | Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1, Trastuzumab, Pertuzumab, T-DM1 |
| PaclitaxelAlso: TaxolDay 1, 8 and 15; every 4 weeks for ≥4 months 90 mg/m2 i.v. infusion | Drug | Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1 |
| VinorelbineAlso: NavelbineFirst 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 | Drug | Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1 |
| T-DM1Also: Trastuzumab emtansineEvery 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.) | Drug | Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1, Trastuzumab, Pertuzumab, T-DM1 |
Primary outcome
Overall survival (OS) - Analysis Population: ITT Population 1
Time frame: 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
15 secondary outcomes
OS - Analysis Population: ITT Population 2
Time frame: 24 months
Progression Free Survival (PFS) of first-line treatment ignoring first Central Nervous System (CNS) lesion
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 )
Overall survival OS
Time frame: OS will be calculated from randomization until death (estimated median: 32 months)
Objective response (OR) of first-line treatment (based on investigator assessment)
Time frame: 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)
Time frame: 6 months (DC is defined as CR, PR or SD for 6 months after randomization and no PD at 6 month after randomization)
OR of second-line treatment (based on investigator assessment)
Time frame: 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)
DC of second-line treatment (based on investigator assessment)
Time frame: 6 months (DC is defined as the response CR, PR or SD for 6 months after registration of second-line treatment)
Adverse events (AEs) according to the NCI CTCAE v4.0 of first-line treatment
Time frame: Throughout first-line treatment (estimated up to 16 months)
AEs according to the NCI CTCAE v4.0 of second-line treatment
Time frame: Throughout second-line treatment (estimated up to 9 months)
AEs grade ≥2 until first progression (ignoring first CNS lesion)
Time frame: Throughout first-line treatment (estimated up to 16 months)
Quality of Life (QoL)
Time frame: 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
Time frame: 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2021.
- Derived from this study: PubMed 37561451Huober 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jens Huober, MD study chair
University of Ulm
Patrik Weder, MD study chair
Cantonal Hospital of St. Gallen
Hervé Bonnefoi, Prof study chair
Institut Bergonié Bordeaux
71 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab, Pertuzumab and Paclitaxel in people with Metastatic Breast Cancer, run by Swiss Cancer Institute at 71 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 71 sites in France, Switzerland, Netherlands, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (OS) - Analysis Population: ITT Population 1 (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01835236, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2021.