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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01996267
Recruitment Status : Active, not recruiting
First Posted : November 27, 2013
Last Update Posted : February 3, 2017
Roche Pharma AG
Borstkanker Onderzoek Groep
Information provided by (Responsible Party):
The Netherlands Cancer Institute

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

Condition or disease Intervention/treatment Phase
Breast Cancer HER2 Positive Drug: PTC+Pertuzumab Drug: FEC-T+Pertuzumab Phase 3

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  (Clinical Trial)
Actual Enrollment : 437 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Optimizing Neoadjuvant Systemic Treatment for HER2 Positive Breast Cancer - the TRAIN-2 Study
Study Start Date : December 2013
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Pertuzumab
U.S. FDA Resources

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:
  • 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
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

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. 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

  2. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01996267

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

Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT01996267     History of Changes
Other Study ID Numbers: M13TRT
First Posted: November 27, 2013    Key Record Dates
Last Update Posted: February 3, 2017
Last Verified: February 2017

Keywords provided by The Netherlands Cancer Institute:
breast cancer
HER2 positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors