Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2

NCT ID: NCT01996267

Last Updated: 2024-03-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 437 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2030-12-31

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.

Conditions

Breast Cancer; HER2 Positive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

FEC-T+Pertuzumab

Intervention Type: DRUG

Cycle is repeated every 21 days

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

Group Type: ACTIVE_COMPARATOR

PTC+Pertuzumab

Intervention Type: DRUG

Cycle repeated every 21 days

Interventions

PTC+Pertuzumab

Cycle repeated every 21 days

Intervention Type: DRUG

FEC-T+Pertuzumab

Cycle is repeated every 21 days

Intervention Type: DRUG

Other Intervention 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; 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

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.

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

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Borstkanker Onderzoek Groep

NETWORK

Sponsor Role: collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gabe S Sonke, MD

Role: PRINCIPAL_INVESTIGATOR

Antoni van Leeuwenhoek, Amsterdam

Locations

Jeroen Bosch Hospital

's-Hertogenbosch, , Netherlands

MCA

Alkmaar, , Netherlands

ZGT

Almelo, , Netherlands

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

AZVU

Amsterdam, , Netherlands

OLVG

Amsterdam, , Netherlands

Rode Kruis Ziekenhuis

Beverwijk, , Netherlands

Amphia ziekenhuis

Breda, , Netherlands

Reinier de Graaf Groep

Delft, , Netherlands

Deventer ziekenhuis

Deventer, , Netherlands

Ziekenhuis Gelderse Vallei

Ede, , Netherlands

Catharina Ziekenhuis

Eindhoven, , Netherlands

Maxima Medisch Centrum

Eindhoven, , Netherlands

St Anna Geldrop

Geldrop, , Netherlands

Orbis Medisch Centrum

Geleen, , Netherlands

Groene Hart

Gouda, , Netherlands

Kennemer Gasthuis

Haarlem, , Netherlands

Atrium Medisch Centrum Parkstad

Heerlen, , Netherlands

Spaarne ziekenhuis

Hoofddorp, , Netherlands

Westfries Gasthuis

Hoorn, , Netherlands

MCL

Leeuwarden, , Netherlands

LUMC

Leiden, , Netherlands

Diaconessenhuis Meppel

Meppel, , Netherlands

Canisius-Wilhelmina Hospital

Nijmegen, , Netherlands

Waterlandziekenhuis

Purmerend, , Netherlands

Vlietland Ziekenhuis

Schiedam, , Netherlands

Haga

The Hague, , Netherlands

Bronovo Ziekenhuis

The Hague, , Netherlands

St. Elisabeth

Tilburg, , Netherlands

Diaconessenhuis Utrecht

Utrecht, , Netherlands

VieCuri Medisch Centrum voor Noord-Limburg

Venlo, , Netherlands

Zaans Medisch Centrum

Zaandam, , Netherlands

Isala Klinieken

Zwolle, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 34014249 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30413379 (View on PubMed)

Other Identifiers

M13TRT

Identifier Type: -

Identifier Source: org_study_id