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Breast CancerPhase 3TRAIN-2NCT01996267

Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2

A Phase 3 study testing PTC+Pertuzumab and FEC-T+Pertuzumab in people with Breast Cancer and HER2 Positive, run by The Netherlands Cancer Institute at 33 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 study compares two schedules of upfront chemotherapy in HER positive breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, HER2 Positive
What is being tested?
PTC+Pertuzumab and FEC-T+Pertuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
437 participants
Where
33 sitesNetherlands
Study dates
Dec 2013to Dec 2030
Phase
Phase 3
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 infiltrating breast cancer
  • Stage II or stage III disease. Nodal status must be examined by ultrasound, fine needle aspiration, sentinel node biopsy, or FDG-PET scan.
  • Overexpression and/or amplification of HER2 in an invasive component of the core biopsy, according to one of the following definitions:
  • •>30% of invasive tumor cells showing strong complete circumferential membrane staining (score 3+)
  • •HER2 gene amplification defined as >6 HER2 gene copies per nucleus by in situ hybridization.
  • Age ≥18
Show all 14Show fewer
  • Eastern Cooperative Oncology Group performance status ≤1
  • Adequate bone marrow function (ANC >1.5 x 109/l, platelets >100 x 109/l)
  • Adequate hepatic function (ALAT, ASAT and bilirubin <2.5 times upper limit of normal)
  • Adequate renal function (creatinine clearance >50 ml/min)
  • LVEF ≥50% measured by echocardiography or MUGA
  • Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • Absence of any medical condition that would place the patient at unusual risk.
  • Signed written informed consent

Who cannot join

  • previous radiation therapy or chemotherapy
  • other malignancy except carcinoma in situ, unless the other malignancy was treated ≥5 years ago with curative intent without the use of chemotherapy or radiation therapy.
  • current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection
  • evidence of distant metastases. Evaluation of the presence of distant metastases may include chest X-ray, liver ultrasound, isotope bone-scan, CT-scan of chest and abdomen and/or FDG-PET scan, according to local procedures.
  • evidence of bilateral infiltrating breast cancer. Evaluation of the presence of bilateral infiltrating breast cancer may include mammography, breast ultrasound and/or MRI breast.
  • concurrent anti-cancer treatment or another investigational drug.

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

Netherlands33 sites

  • Jeroen Bosch Hospital

    's-Hertogenbosch

  • MCA

    Alkmaar, 1815 JD

  • ZGT

    Almelo, 7609 PP

  • Antoni van Leeuwenhoek

    Amsterdam, 1066 CX

  • AZVU

    Amsterdam, 1081 HV

  • OLVG

    Amsterdam, 1090 HM

  • Rode Kruis Ziekenhuis

    Beverwijk, 1940 EB

  • Amphia ziekenhuis

    Breda, 4819 EV

  • Reinier de Graaf Groep

    Delft, 2625 AD

  • Deventer ziekenhuis

    Deventer, 7416 SE

  • Ziekenhuis Gelderse Vallei

    Ede, 6716 RP

  • Catharina Ziekenhuis

    Eindhoven, 5602 ZA

  • Maxima Medisch Centrum

    Eindhoven, 5631 BM

  • St Anna Geldrop

    Geldrop, 5664 EH

  • Orbis Medisch Centrum

    Geleen, 6162 BG

  • Groene Hart

    Gouda, 2803 HH

  • Kennemer Gasthuis

    Haarlem, 2035 RC

  • Atrium Medisch Centrum Parkstad

    Heerlen, 6401 CX

  • Spaarne ziekenhuis

    Hoofddorp, 2134 TM

  • Westfries Gasthuis

    Hoorn, 1624 NP

  • MCL

    Leeuwarden, 8934 AD

  • LUMC

    Leiden, 2300 RC

  • Diaconessenhuis Meppel

    Meppel, 7943 KA

  • Canisius-Wilhelmina Hospital

    Nijmegen

  • Waterlandziekenhuis

    Purmerend, 1441 RN

  • Vlietland Ziekenhuis

    Schiedam, 3100 AE

  • Haga

    The Hague, 2545 CH

  • Bronovo Ziekenhuis

    The Hague, 2597 AX

  • St. Elisabeth

    Tilburg, 5022 GC

  • Diaconessenhuis Utrecht

    Utrecht, 3582 KE

  • VieCuri Medisch Centrum voor Noord-Limburg

    Venlo

  • Zaans Medisch Centrum

    Zaandam, 1502 DV

  • Isala Klinieken

    Zwolle, 8025 AB

Other trials in Netherlands

About this study

Official title: Optimizing Neoadjuvant Systemic Treatment for HER2 Positive Breast Cancer - the TRAIN-2 Study

This study compares two schedules of upfront chemotherapy in HER positive breast cancer.

Read the detailed description

Upfront trastuzumab treatment is beneficial to patients with HER2 positive breast cancer. The potential synergistic cardiotoxicity of trastuzumab and anthracyclines has led to the development of non-anthracycline containing regimens, which have shown high pathologic complete response rates. Anthracyclines remain very active in HER2 positive breast cancer, however, and increasing evidence now supports safe combination of trastuzumab and epirubicin. Therefore, the addition of epirubicin to a non-anthracycline containing regimen may further improve outcome for patients with HER2 positive breast cancer.

Several reports confirmed benefit of dual HER2 blockade by adding pertuzumab to a trastuzumab containing neoadjuvant regimen. The results of the combined treatment in the Neosphere study, however, are similar to what we found in a phase II trial using a weekly paclitaxel, trastuzumab, carboplatin combination with pCR rates of approximately 44%. Adding pertuzumab to this regimen is likely to also increase the high pCR rate and to add substantial benefit to patients.

Being tested
PTC+Pertuzumab, FEC-T+Pertuzumab
Keywords
neoadjuvant, breast cancer, HER2 positive
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+PertuzumabDrug

    Also called Paclitaxel; 80 mg/m2; day 1,8, Trastuzumab; 6 mg/kg (loading dose 8 mg/kg); day 1, Carboplatin; AUC=6; day 1, Pertuzumab; 420 mg (loading dose 840 mg); day 1

    Cycle repeated every 21 days

  • FEC-T+PertuzumabDrug

    Also called Fluorouracil; 500 mg/m2; day 1, Epirubicine; 90 mg/m2; day 1, Cyclophosphamide 500 mg/m2; day 1, Trastuzumab; 6 mg/kg (loading dose 8 mg/kg)

    Cycle is repeated every 21 days

Study groups in NCT01996267
Study groupRoleWhat they receive
FEC-T +PertuzumabActive comparatorFluorouracil; 500 mg/m2; day 1 Epirubicine; 90 mg/m2; day 1 Cyclophosphamide; 500 mg/m2; day 1 Trastuzumab; 6 mg/kg (loading dose 8 mg/kg) Pertuzumab; 420 mg (loading dose 840 mg); day 1 Cycle is repeated every 21 days
Receives: Drug: FEC-T+Pertuzumab
PTC+PertuzumabActive comparatorPaclitaxel; 80 mg/m2; day 1,8 Trastuzumab; 6 mg/kg (loading dose 8 mg/kg); day 1 Carboplatin; AUC=6; day 1 Pertuzumab; 420 mg (loading dose 840 mg); day 1 Cycle repeated every 21 days
Receives: Drug: PTC+Pertuzumab

What is being measured

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

  1. Number of patients with pathological complete response

    To compare the efficacy of six cycles neoadjuvant PTC plus pertuzumab preceded by either three cycles of FEC-T plus pertuzumab or three cycles of PTC plus pertuzumab in HER2 positive breast cancer

    Measured: at week 30

Secondary outcomes (2)

  1. Number of patients with grade >2 adverse events as a measure of safety and tolerability

    to describe the safety of the various regimens toxicity is compared between the two arms

    Measured: up to week 35

  2. identify prognostic and predictive biomarkers for pCR

    To identify prognostic and predictive biomarkers for pCR after neoadjuvant treatment

    Measured: within one year after end of treatment

Timeline

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

  1. First posted27 Nov 2013 (estimated)
  2. Study startDec 2013
  3. Primary completionDec 2018
  4. Study completionDec 2030 (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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
437 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01996267
Sponsor's protocol ID
M13TRT
Acronym
TRAIN-2
Status last verified
Mar 2024
First submitted
18 Nov 2013
Last updated
29 Mar 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • van der Voort A, van Ramshorst MS, van Werkhoven ED, Mandjes IA, Kemper I, Vulink AJ, Oving IM, Honkoop AH, Tick LW, van de Wouw AJ, Mandigers CM, van Warmerdam LJ, Wesseling J, Vrancken Peeters MT, Linn SC, Sonke GS. Three-Year Follow-up of Neoadjuvant Chemotherapy With or Without Anthracyclines in the Presence of Dual ERBB2 Blockade in Patients With ERBB2-Positive Breast Cancer: A Secondary Analysis of the TRAIN-2 Randomized, Phase 3 Trial. JAMA Oncol. 2021 Jul 1;7(7):978-984. doi: 10.1001/jamaoncol.2021.1371.

    PubMed 34014249

  • van Ramshorst MS, van der Voort A, van Werkhoven ED, Mandjes IA, Kemper I, Dezentje VO, Oving IM, Honkoop AH, Tick LW, van de Wouw AJ, Mandigers CM, van Warmerdam LJ, Wesseling J, Vrancken Peeters MT, Linn SC, Sonke GS; Dutch Breast Cancer Research Group (BOOG). Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 Dec;19(12):1630-1640. doi: 10.1016/S1470-2045(18)30570-9. Epub 2018 Nov 6.

    PubMed 30413379

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing PTC+Pertuzumab and FEC-T+Pertuzumab in people with Breast Cancer and HER2 Positive, run by The Netherlands Cancer Institute at 33 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 14 inclusion and 6 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 29 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Number of patients with pathological complete response (time frame: at week 30). 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 NCT01996267, 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 29 Mar 2024; AzTrials last refreshed its copy on 6 Nov 2026.

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