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

NCT ID: NCT03820063

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 462 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-27
• Study Completion Date: 2032-05-01

Brief 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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PTC-Pz

• 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.

Group Type: EXPERIMENTAL

PTC-Pz

Intervention Type: DRUG

• 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.

Interventions

PTC-Pz

• 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed primairy infiltrating breast cancer.

2. Stage II or Ill disease.

3. Overexpression and/or amplification of HER2 in an invasive component of the core biopsy.

4. Age <:18

5. ECOG Group performance status

6. LVEF >50% measured by echocardiography, MRI or MUGA

7. Known HR-status ( in percentages)

Exclusion Criteria

1. Previous radiation therapy of chemotherapy

2. Pregnancy or breastfeeding

3. Evidence of distant metastases

4. Evidence of bilateral infiltrating breast cancer

5. Concurrent anti-cancer treatment or another investigational drug

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

BOOG Study Center

OTHER

Sponsor Role: collaborator

Borstkanker Onderzoek Groep

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

G S Sonke, MD

Role: PRINCIPAL_INVESTIGATOR

NKI-AvL

A E van Leeuwen- Stok, PhD

Role: STUDY_DIRECTOR

BOOG Study Center

Locations

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Noordwest Ziekenhuisgroep

Alkmaar, , Netherlands

Ziekenhuisgroep Twente

Almelo, , Netherlands

Meander Medisch Centrum

Amersfoort, , Netherlands

Ziekenhuis Amstelland

Amstelveen, , Netherlands

Amsterdam UMC

Amsterdam, , Netherlands

NKI-AVL

Amsterdam, , Netherlands

OLVG

Amsterdam, , Netherlands

Gelre ziekenhuizen

Apeldoorn, , Netherlands

Rijnstate

Arnhem, , Netherlands

Rode Kruis Ziekenhuis

Beverwijk, , Netherlands

Alexander Monro ziekenhuis

Bilthoven, , Netherlands

Amphia Ziekenhuis

Breda, , Netherlands

Reinier de Graaf Groep

Delft, , Netherlands

Deventer ziekenhuis

Deventer, , Netherlands

van Weel Bethesda

Dirksland, , Netherlands

Nij Smellinghe

Drachten, , Netherlands

Ziekenhuisvoorziening Gelderse Vallei

Ede, , Netherlands

Catharina ziekenhuis

Eindhoven, , Netherlands

Maxima Medisch Centrum

Eindhoven, , Netherlands

Sint Annaziekenhuis

Geldrop, , Netherlands

RIVAS Beatrixziekenhuis

Gorinchem, , Netherlands

Groene Hart Ziekenhuis

Gouda, , Netherlands

Martini ziekenhuis

Groningen, , Netherlands

Ziekenhuis St. Jansdal

Harderwijk, , Netherlands

Tjongerschans

Heerenveen, , Netherlands

Zuyderland Medisch Centrum

Heerlen, , Netherlands

Elkerliek ziekenhuis

Helmond, , Netherlands

Tergooi

Hilversum, , Netherlands

Spaarne Gasthuis

Hoofddorp, , Netherlands

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

MUMC

Maastricht, , Netherlands

Sint Antonius ziekenhuis

Nieuwegein, , Netherlands

Canisius Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

Bernhoven

Oss, , Netherlands

Stichting ziekenhuizen West-Friesland en Waterland

Purmerend, , Netherlands

Laurentius ziekenhuis

Roermond, , Netherlands

Erasmus MC, Universitair Medisch Centrum Rotterdam

Rotterdam, , Netherlands

Franciscus Gasthuis en Vlietland

Rotterdam, , Netherlands

Ikazia Ziekenhuis

Rotterdam, , Netherlands

Maasstadziekenhuis

Rotterdam, , Netherlands

ZorgSaam

Terneuzen, , Netherlands

Haaglanden MC

The Hague, , Netherlands

Haga Ziekenhuis

The Hague, , Netherlands

Rivierenland Ziekenhuis

Tiel, , Netherlands

Elisabeth TweeSteden ziekenhuis

Tilburg, , Netherlands

Diakonessenhuis Utrecht

Utrecht, , Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

VieCurie Medisch Centrum voor Noord-Limburg

Venlo, , Netherlands

SKB Ziekenhuis Winterswijk

Winterswijk, , Netherlands

Zaans Medisch Centrum

Zaandam, , Netherlands

Isala Klinieken

Zwolle, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 38588682 (View on PubMed)

Other Identifiers

BOOG 2018-01

Identifier Type: -

Identifier Source: org_study_id