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Breast CancerPhase 2TRAIN-3NCT03820063

Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study

A Phase 2 study testing PTC-Pz in people with Breast Cancer, run by Borstkanker Onderzoek Groep at 52 sites in Netherlands.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a multicenter, single arm, phase II study evaluating the efficacy of image-guided de-escalating neoadjuvant treatment with paclitaxel, Herceptin® (trastuzumab), carboplatin, and pertuzumab (PTC-Ptz) in stage II-Ill HER2-positive breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
PTC-Pz
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
462 participants
Where
52 sitesNetherlands
Study dates
27 Feb 2019to 1 May 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed primairy infiltrating breast cancer.
  • Stage II or Ill disease.
  • Overexpression and/or amplification of HER2 in an invasive component of the core biopsy.
  • Age <:18
  • ECOG Group performance status
  • LVEF >50% measured by echocardiography, MRI or MUGA
  • Known HR-status ( in percentages)

Who cannot join

  • Previous radiation therapy of chemotherapy
  • Pregnancy or breastfeeding
  • Evidence of distant metastases
  • Evidence of bilateral infiltrating breast cancer
  • Concurrent anti-cancer treatment or another investigational drug

Trial locations and contacts

52 sites in 1 country.

52 sites in 1 country

Netherlands52 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch

  • Noordwest Ziekenhuisgroep

    Alkmaar

  • Ziekenhuisgroep Twente

    Almelo

  • Meander Medisch Centrum

    Amersfoort

  • Ziekenhuis Amstelland

    Amstelveen

  • Amsterdam UMC

    Amsterdam

  • NKI-AVL

    Amsterdam

  • OLVG

    Amsterdam

  • Gelre ziekenhuizen

    Apeldoorn

  • Rijnstate

    Arnhem

  • Rode Kruis Ziekenhuis

    Beverwijk

  • Alexander Monro ziekenhuis

    Bilthoven

  • Amphia Ziekenhuis

    Breda

  • Reinier de Graaf Groep

    Delft

  • Deventer ziekenhuis

    Deventer

  • van Weel Bethesda

    Dirksland

  • Nij Smellinghe

    Drachten

  • Ziekenhuisvoorziening Gelderse Vallei

    Ede

  • Catharina ziekenhuis

    Eindhoven

  • Maxima Medisch Centrum

    Eindhoven

  • Sint Annaziekenhuis

    Geldrop

  • RIVAS Beatrixziekenhuis

    Gorinchem

  • Groene Hart Ziekenhuis

    Gouda

  • Martini ziekenhuis

    Groningen

  • Ziekenhuis St. Jansdal

    Harderwijk

  • Tjongerschans

    Heerenveen

  • Zuyderland Medisch Centrum

    Heerlen

  • Elkerliek ziekenhuis

    Helmond

  • Tergooi

    Hilversum

  • Spaarne Gasthuis

    Hoofddorp

  • Medisch Centrum Leeuwarden

    Leeuwarden

  • MUMC

    Maastricht

  • Sint Antonius ziekenhuis

    Nieuwegein

  • Canisius Wilhelmina Ziekenhuis

    Nijmegen

  • Bernhoven

    Oss

  • Stichting ziekenhuizen West-Friesland en Waterland

    Purmerend

  • Laurentius ziekenhuis

    Roermond

  • Erasmus MC, Universitair Medisch Centrum Rotterdam

    Rotterdam

  • Franciscus Gasthuis en Vlietland

    Rotterdam

  • Ikazia Ziekenhuis

    Rotterdam

  • Maasstadziekenhuis

    Rotterdam

  • ZorgSaam

    Terneuzen

  • Haaglanden MC

    The Hague

  • Haga Ziekenhuis

    The Hague

  • Rivierenland Ziekenhuis

    Tiel

  • Elisabeth TweeSteden ziekenhuis

    Tilburg

  • Diakonessenhuis Utrecht

    Utrecht

  • Universitair Medisch Centrum Utrecht

    Utrecht

  • VieCurie Medisch Centrum voor Noord-Limburg

    Venlo

  • SKB Ziekenhuis Winterswijk

    Winterswijk

  • Zaans Medisch Centrum

    Zaandam

  • Isala Klinieken

    Zwolle

Other trials in Netherlands

About this study

This is a multicenter, single arm, phase II study evaluating the efficacy of image-guided de-escalating neoadjuvant treatment with paclitaxel, Herceptin® (trastuzumab), carboplatin, and pertuzumab (PTC-Ptz) in stage II-Ill HER2-positive breast cancer.

Read the detailed description

High pathological complete response (pCR)-rates are seen using different neoadjuvant chemotherapy schedules with trastuzumab and pertuzumab in HER2-positive stage II - III breast cancer patients. Total pCR rates in breast and axilla have been described as high as 64%, and with an even higher rate of >80% in patients with HER2-positive and hormone receptor (HR) negative tumors. PCR is associated with better long-term outcomes in patients with HER2-positive breast cancer. Three year progression-free survival ranges between 85-90%. Neoadjuvant treatment of HER2-positive breast cancer typically consists of six to nine cycles of treatment. Longer duration of treatment is associated with higher pCR-rates but gives more toxicity. Pathological complete responses are sometimes seen after only 10-12 days of neoadjuvant treatment. It is therefore important to investigate which patients can safely be treated with less than six cycles of chemotherapy and who requires more than six cycles for maximum activity.

The radiologic response of a breast tumor after neoadjuvant therapy is predictive of the pathologic response, although the accuracy differs between breast cancer subtypes. It is hypothesized that patients with an early complete radiologic response may not benefit from additional chemotherapy and can be referred for early surgery. Patients who have not achieved pCR after early surgery despite radiologic complete response (rCR) are candidates for further adjuvant chemotherapy to complete the initially planned number of treatment cycles and maintain maximum treatment activity. Imaged guided de-escalation in which the number of treatment cycles is determined by the radiologic response could thus reduce toxicity in neoadjuvant treatment while maintaining activity.

This study will evaluate the efficacy of image-guided de-escalation of neoadjuvant chemotherapy in patients with HER2-positive breast cancer.

To maintain efficacy, patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1. Patients who achieve early pCR will continue treatment with Herceptin® and pertuzumab to complete one full year of treatment.

Conditions
Breast Cancer
Being tested
PTC-Pz
Keywords
neo adjuvant, HER2 positive, de-escalation
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PTC-PzDrug

    • Paclitaxel 80mg/m2 administered intravenously on day 1 and day 8
    • Herceptin® 6mg/kg administered intravenously on day 1 (loading dose 8mg/kg) or Herceptin® administered subcutaneously 600mg on day 1
    • Carboplatin AUC 6mg•ml/min administered intravenously on day 1
    • Pertuzumab 420mg administered intravenously on day 1 (loading dose 840mg)
    • Treatment cycles are repeated on day 22

    In case of non pCR; Adjuvant T-DM1, 3.6mg/kg Q 22 days, for 14 cycles.

Study groups in NCT03820063
Study groupRoleWhat they receive
PTC-PzExperimental* Paclitaxel 80mg/m2 administered intravenously on day 1 and day 8 * Herceptin® 6mg/kg administered intravenously on day 1 (loading dose 8mg/kg) or Herceptin® administered subcutaneously 600mg on day 1 * Carboplatin AUC 6mg•ml/min administered intravenously on day 1 * Pertuzumab 420mg administered intravenously on day 1 (loading dose 840mg) * Treatment cycles are repeated on day 22 Patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1.
Receives: Drug: PTC-Pz

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event free survival at three years

    Number of patients without progression of disease recurrence, second primary or death

    Measured: 3 years

Secondary outcomes (10)

  1. Overall survival at three years

    Number of patients alive at three years

    Measured: 3 years

  2. Pathologic complete response in breast and axilla

    Number of patients with absence of invasive tumor cells in breast and axilla at surgery

    Measured: an average of 6 months

  3. Radiologic complete response

    Number of patients with absence of pathologic enhancement on MRI

    Measured: an average of 6 months

  4. Number of neoadjuvant chemotherapy cycles administered

    Number of neoadjuvant chemotherapy cycles administered per patient

    Measured: an average of 1 year

  5. Number of radical and non-radical resections

    Number of patients with radical and non-radical resections

    Measured: an average of 6 months

  6. Incidence and severity of adverse events

    Number of patients with toxicity grade >= 3 (CTCAE v5.0) until 30 days after last adjuvant administration

    Measured: an average of 1 year

  7. Incidence and severity of cardiotoxicity and neuropathy

    Number of patients with cardiotoxicity and neuropathy grade >= 2 (CTCAE v5.0) until 30 days after last adjuvant administration

    Measured: an average of 1 year

  8. Incidence of symptomatic LVSD (heart failure),

    Number of patients with an asymptomatic decline in LVEF requiring treatment or leading to discontinuation of pertuzumab and Herceptin, or a decrease ≥10 percentage points from baseline to a LVEF <50%

    Measured: an average of 1 year

  9. Grade ≥3 laboratory test abnormalities

    Number of patients with Grade ≥3 laboratory test abnormalities

    Measured: an average of 1 year

  10. Incidence of number of tumor positive Vacuum Assisted Core Biopsy

    Number of patients with tumor present at Vacuum Assisted Core Biopsy at the moment of radiological complete response on MRI

    Measured: an average 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jan 2019
  2. Study start27 Feb 2019
  3. Primary completion15 Nov 2022
  4. Study completion1 May 2032 (estimated)

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
Not applicable
Intervention model
Single group
Model description
neoadjuvant courses PTC-Ptz; adjuvant courses Ptz (pCR) or T-DM1 (non-pCR)
Masking
None (open label)
Enrolment
462 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03820063
Sponsor's protocol ID
BOOG 2018-01
Acronym
TRAIN-3
Status last verified
Sep 2026
First submitted
25 Jan 2019
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Louis FM, van der Voort A, van Ramshorst MS, Daletzakis A, Mandjes IA, Kemper I, Agterof MJ, van der Steeg WA, Heijns JB, van Bekkum ML, Siemerink EJM, Kuijer PM, Scholten A, Wesseling J, Vrancken Peeters MTFD, Egeler MD, van de Poll-Franse LV, Mann RM, Sonke GS; Dutch Breast Cancer Research Group (BOOG). MRI-based personalisation of neoadjuvant chemotherapy duration in HER2-positive early breast cancer (TRAIN-3): primary results from a multicentre, single-arm, phase 2 study. Lancet Oncol. 2026 Mar;27(3):349-360. doi: 10.1016/S1470-2045(25)00707-7. Epub 2026 Feb 16.

    PubMed 41713473

  • van der Voort A, Louis FM, van Ramshorst MS, Kessels R, Mandjes IA, Kemper I, Agterof MJ, van der Steeg WA, Heijns JB, van Bekkum ML, Siemerink EJ, Kuijer PM, Scholten A, Wesseling J, Vrancken Peeters MTFD, Mann RM, Sonke GS; Dutch Breast Cancer Research Group. MRI-guided optimisation of neoadjuvant chemotherapy duration in stage II-III HER2-positive breast cancer (TRAIN-3): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2024 May;25(5):603-613. doi: 10.1016/S1470-2045(24)00104-9. Epub 2024 Apr 5.

    PubMed 38588682

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PTC-Pz in people with Breast Cancer, run by Borstkanker Onderzoek Groep at 52 sites in Netherlands.

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 7 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in Netherlands. 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?

This study is still under way. Results are not available in the source record yet.

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?

Event free survival at three years (time frame: 3 years). 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 NCT03820063, which also lists 2 linked publications.

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 5 Oct 2026.

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