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

Primary Purpose

Breast Cancer, HER2 Positive

Status
Active
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
PTC+Pertuzumab
FEC-T+Pertuzumab
Sponsored by
The Netherlands Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring neoadjuvant, breast cancer, HER2 positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • MCA
  • ZGT
  • Antoni van Leeuwenhoek
  • AZVU
  • OLVG
  • Rode Kruis Ziekenhuis
  • Amphia ziekenhuis
  • Reinier de Graaf Groep
  • Jeroen Bosch Hospital
  • Haga
  • Bronovo Ziekenhuis
  • Deventer ziekenhuis
  • Ziekenhuis Gelderse Vallei
  • Catharina Ziekenhuis
  • Maxima Medisch Centrum
  • St Anna Geldrop
  • Orbis Medisch Centrum
  • Groene Hart
  • Kennemer Gasthuis
  • Atrium Medisch Centrum Parkstad
  • Spaarne ziekenhuis
  • Westfries Gasthuis
  • MCL
  • LUMC
  • Diaconessenhuis Meppel
  • Canisius-Wilhelmina Hospital
  • Waterlandziekenhuis
  • Vlietland Ziekenhuis
  • St. Elisabeth
  • Diaconessenhuis Utrecht
  • VieCuri Medisch Centrum voor Noord-Limburg
  • Zaans Medisch Centrum
  • Isala Klinieken

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

FEC-T +Pertuzumab

PTC+Pertuzumab

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
identify prognostic and predictive biomarkers for pCR
To identify prognostic and predictive biomarkers for pCR after neoadjuvant treatment

Full Information

First Posted
November 18, 2013
Last Updated
March 21, 2023
Sponsor
The Netherlands Cancer Institute
Collaborators
Roche Pharma AG, Borstkanker Onderzoek Groep
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1. Study Identification

Unique Protocol Identification Number
NCT01996267
Brief Title
Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2
Acronym
TRAIN-2
Official Title
Optimizing Neoadjuvant Systemic Treatment for HER2 Positive Breast Cancer - the TRAIN-2 Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2013 (undefined)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
December 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Netherlands Cancer Institute
Collaborators
Roche Pharma AG, Borstkanker Onderzoek Groep

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, HER2 Positive
Keywords
neoadjuvant, breast cancer, HER2 positive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
437 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FEC-T +Pertuzumab
Arm Type
Active Comparator
Arm Description
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
Arm Title
PTC+Pertuzumab
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
PTC+Pertuzumab
Other Intervention Name(s)
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
Intervention Description
Cycle repeated every 21 days
Intervention Type
Drug
Intervention Name(s)
FEC-T+Pertuzumab
Other Intervention Name(s)
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
Intervention Description
Cycle is repeated every 21 days
Primary Outcome Measure Information:
Title
Number of patients with pathological complete response
Description
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
Time Frame
at week 30
Secondary Outcome Measure Information:
Title
Number of patients with grade >2 adverse events as a measure of safety and tolerability
Description
to describe the safety of the various regimens toxicity is compared between the two arms
Time Frame
up to week 35
Title
identify prognostic and predictive biomarkers for pCR
Description
To identify prognostic and predictive biomarkers for pCR after neoadjuvant treatment
Time Frame
within one year after end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gabe S Sonke, MD
Organizational Affiliation
Antoni van Leeuwenhoek, Amsterdam
Official's Role
Principal Investigator
Facility Information:
Facility Name
MCA
City
Alkmaar
ZIP/Postal Code
1815 JD
Country
Netherlands
Facility Name
ZGT
City
Almelo
ZIP/Postal Code
7609 PP
Country
Netherlands
Facility Name
Antoni van Leeuwenhoek
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
AZVU
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
OLVG
City
Amsterdam
ZIP/Postal Code
1090 HM
Country
Netherlands
Facility Name
Rode Kruis Ziekenhuis
City
Beverwijk
ZIP/Postal Code
1940 EB
Country
Netherlands
Facility Name
Amphia ziekenhuis
City
Breda
ZIP/Postal Code
4819 EV
Country
Netherlands
Facility Name
Reinier de Graaf Groep
City
Delft
ZIP/Postal Code
2625 AD
Country
Netherlands
Facility Name
Jeroen Bosch Hospital
City
Den Bosch
Country
Netherlands
Facility Name
Haga
City
Den Haag
ZIP/Postal Code
2545 CH
Country
Netherlands
Facility Name
Bronovo Ziekenhuis
City
den Haag
ZIP/Postal Code
2597 AX
Country
Netherlands
Facility Name
Deventer ziekenhuis
City
Deventer
ZIP/Postal Code
7416 SE
Country
Netherlands
Facility Name
Ziekenhuis Gelderse Vallei
City
Ede
ZIP/Postal Code
6716 RP
Country
Netherlands
Facility Name
Catharina Ziekenhuis
City
Eindhoven
ZIP/Postal Code
5602 ZA
Country
Netherlands
Facility Name
Maxima Medisch Centrum
City
Eindhoven
ZIP/Postal Code
5631 BM
Country
Netherlands
Facility Name
St Anna Geldrop
City
Geldrop
ZIP/Postal Code
5664 EH
Country
Netherlands
Facility Name
Orbis Medisch Centrum
City
Geleen
ZIP/Postal Code
6162 BG
Country
Netherlands
Facility Name
Groene Hart
City
Gouda
ZIP/Postal Code
2803 HH
Country
Netherlands
Facility Name
Kennemer Gasthuis
City
Haarlem
ZIP/Postal Code
2035 RC
Country
Netherlands
Facility Name
Atrium Medisch Centrum Parkstad
City
Heerlen
ZIP/Postal Code
6401 CX
Country
Netherlands
Facility Name
Spaarne ziekenhuis
City
Hoofddorp
ZIP/Postal Code
2134 TM
Country
Netherlands
Facility Name
Westfries Gasthuis
City
Hoorn
ZIP/Postal Code
1624 NP
Country
Netherlands
Facility Name
MCL
City
Leeuwarden
ZIP/Postal Code
8934 AD
Country
Netherlands
Facility Name
LUMC
City
Leiden
ZIP/Postal Code
2300 RC
Country
Netherlands
Facility Name
Diaconessenhuis Meppel
City
Meppel
ZIP/Postal Code
7943 KA
Country
Netherlands
Facility Name
Canisius-Wilhelmina Hospital
City
Nijmegen
Country
Netherlands
Facility Name
Waterlandziekenhuis
City
Purmerend
ZIP/Postal Code
1441 RN
Country
Netherlands
Facility Name
Vlietland Ziekenhuis
City
Schiedam
ZIP/Postal Code
3100 AE
Country
Netherlands
Facility Name
St. Elisabeth
City
Tilburg
ZIP/Postal Code
5022 GC
Country
Netherlands
Facility Name
Diaconessenhuis Utrecht
City
Utrecht
ZIP/Postal Code
3582 KE
Country
Netherlands
Facility Name
VieCuri Medisch Centrum voor Noord-Limburg
City
Venlo
Country
Netherlands
Facility Name
Zaans Medisch Centrum
City
Zaandam
ZIP/Postal Code
1502 DV
Country
Netherlands
Facility Name
Isala Klinieken
City
Zwolle
ZIP/Postal Code
8025 AB
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
34014249
Citation
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.
Results Reference
derived
PubMed Identifier
30413379
Citation
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.
Results Reference
derived

Learn more about this trial

Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2

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