Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2 (TRAIN-2)

March 28, 2024 updated by: The Netherlands Cancer Institute

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

437

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Alkmaar, Netherlands, 1815 JD
        • MCA
      • Almelo, Netherlands, 7609 PP
        • ZGT
      • Amsterdam, Netherlands, 1066 CX
        • Antoni van Leeuwenhoek
      • Amsterdam, Netherlands, 1090 HM
        • OLVG
      • Amsterdam, Netherlands, 1081 HV
        • AZVU
      • Beverwijk, Netherlands, 1940 EB
        • Rode Kruis Ziekenhuis
      • Breda, Netherlands, 4819 EV
        • Amphia Ziekenhuis
      • Delft, Netherlands, 2625 AD
        • Reinier de Graaf Groep
      • Den Bosch, Netherlands
        • Jeroen Bosch Hospital
      • Den Haag, Netherlands, 2545 CH
        • Haga
      • Deventer, Netherlands, 7416 SE
        • Deventer Ziekenhuis
      • Ede, Netherlands, 6716 RP
        • Ziekenhuis Gelderse Vallei
      • Eindhoven, Netherlands, 5631 BM
        • Maxima Medisch Centrum
      • Eindhoven, Netherlands, 5602 ZA
        • Catharina Ziekenhuis
      • Geldrop, Netherlands, 5664 EH
        • St Anna Geldrop
      • Geleen, Netherlands, 6162 BG
        • Orbis Medisch Centrum
      • Gouda, Netherlands, 2803 HH
        • Groene Hart
      • Haarlem, Netherlands, 2035 RC
        • Kennemer Gasthuis
      • Heerlen, Netherlands, 6401 CX
        • Atrium Medisch Centrum Parkstad
      • Hoofddorp, Netherlands, 2134 TM
        • Spaarne Ziekenhuis
      • Hoorn, Netherlands, 1624 NP
        • Westfries Gasthuis
      • Leeuwarden, Netherlands, 8934 AD
        • MCL
      • Leiden, Netherlands, 2300 RC
        • LUMC
      • Meppel, Netherlands, 7943 KA
        • Diaconessenhuis Meppel
      • Nijmegen, Netherlands
        • Canisius-Wilhelmina Hospital
      • Purmerend, Netherlands, 1441 RN
        • Waterlandziekenhuis
      • Schiedam, Netherlands, 3100 AE
        • Vlietland ziekenhuis
      • Tilburg, Netherlands, 5022 GC
        • St. Elisabeth
      • Utrecht, Netherlands, 3582 KE
        • Diaconessenhuis Utrecht
      • Venlo, Netherlands
        • VieCuri Medisch Centrum voor Noord-Limburg
      • Zaandam, Netherlands, 1502 DV
        • Zaans Medisch Centrum
      • Zwolle, Netherlands, 8025 AB
        • ISALA Klinieken
      • den Haag, Netherlands, 2597 AX
        • Bronovo Ziekenhuis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: FEC-T +Pertuzumab
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) Pertuzumab; 420 mg (loading dose 840 mg); day 1 Cycle is repeated every 21 days
Drug: FEC-T+Pertuzumab
Cycle is repeated every 21 days
Other Names:
  • Pertuzumab; 420 mg (loading dose 840 mg); day 1
  • 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)
Active Comparator: PTC+Pertuzumab
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
Drug: PTC+Pertuzumab
Cycle repeated every 21 days
Other Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with pathological complete response
Time Frame: at week 30
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
at week 30

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with grade >2 adverse events as a measure of safety and tolerability
Time Frame: up to week 35
to describe the safety of the various regimens toxicity is compared between the two arms
up to week 35
identify prognostic and predictive biomarkers for pCR
Time Frame: within one year after end of treatment
To identify prognostic and predictive biomarkers for pCR after neoadjuvant treatment
within one year after end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Netherlands Cancer Institute

Collaborators

Roche Pharma AG
Borstkanker Onderzoek Groep

Investigators

  • Principal Investigator: Gabe S Sonke, MD, Antoni van Leeuwenhoek, Amsterdam

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2013

Primary Completion (Actual)

December 1, 2018

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

November 18, 2013

First Submitted That Met QC Criteria

November 21, 2013

First Posted (Estimated)

November 27, 2013

Study Record Updates

Last Update Posted (Actual)

March 29, 2024

Last Update Submitted That Met QC Criteria

March 28, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M13TRT

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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