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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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.
Show all 15Show fewer
  • 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
Show all 30Show fewer
  • 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

Other trials in France

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

Other trials in Switzerland

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

Other trials in Netherlands

Germany1 site

  • Universitäts-Frauenklinik Ulm

    Ulm, 89075

Other trials in Germany

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.

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 groups in NCT01835236
Study groupRoleWhat they receive
Trastuzumab, Pertuzumab, T-DM1Active comparatorFirst line therapy: Trastuzumab, Pertuzumab Second line therapy: T-DM1
Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: T-DM1
Trastuzumab, Pertuzumab, Paclitaxel or Vinorelbine plus T-DM1Active comparatorFirst 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.

  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

    Measured: 24 months

Secondary outcomes (15)

  1. 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

  2. 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 )

  3. 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)

  4. 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)

  5. 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 )

  6. 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)

  7. 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)

  8. 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)

  9. 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)

  10. 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)

  11. 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)

  12. 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)

  13. 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)

  14. 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.

  15. 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.

  1. First posted18 Apr 2013 (estimated)
  2. Study start3 Mar 2013
  3. Primary completion11 Jan 2018
  4. Study completion26 May 2020

Resources

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)
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

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.

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