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NCT01996267 · CITED IN SOURCE DOCUMENTS

Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2024-03-29

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
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.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. 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
    intervention Names
    1. Drug: FEC-T+Pertuzumab
    label
    FEC-T +Pertuzumab
    type
    ACTIVE_COMPARATOR
  2. 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 Names
    1. Drug: PTC+Pertuzumab
    label
    PTC+Pertuzumab
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. PTC+Pertuzumab
    description
    Cycle repeated every 21 days
    name
    PTC+Pertuzumab
    other Names
    1. Paclitaxel; 80 mg/m2; day 1,8
    2. Trastuzumab; 6 mg/kg (loading dose 8 mg/kg); day 1
    3. Carboplatin; AUC=6; day 1
    4. Pertuzumab; 420 mg (loading dose 840 mg); day 1
    type
    DRUG
  2. arm Group Labels
    1. FEC-T +Pertuzumab
    description
    Cycle is repeated every 21 days
    name
    FEC-T+Pertuzumab
    other Names
    1. Fluorouracil; 500 mg/m2; day 1
    2. Epirubicine; 90 mg/m2; day 1
    3. Cyclophosphamide 500 mg/m2; day 1
    4. Trastuzumab; 6 mg/kg (loading dose 8 mg/kg)
    5. Pertuzumab; 420 mg (loading dose 840 mg); day 1
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
437
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. 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
    measure
    Number of patients with pathological complete response
    time Frame
    at week 30
secondary Outcomes
  1. description
    to describe the safety of the various regimens toxicity is compared between the two arms
    measure
    Number of patients with grade >2 adverse events as a measure of safety and tolerability
    time Frame
    up to week 35
  2. description
    To identify prognostic and predictive biomarkers for pCR after neoadjuvant treatment
    measure
    identify prognostic and predictive biomarkers for pCR
    time Frame
    within one year after end of treatment
Full 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.
Source references
references
  1. 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.
    pmid
    34014249
    type
    DERIVED
  2. 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.
    pmid
    30413379
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      occurrences
      1. context exact
        e early breast cancer at a high risk of recurrence. </p> <p id="_3208" tabindex="-1">The randomized, open-label, multicenter <a href="/clinicaltrials/NCT01996267">TRAIN-2</a> trial (NCT01996267) evaluated the optimal chemotherapy backbone to use with neoadjuvant pertuzumab and trastuzumab in patients with stage II to st
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      2. context exact
        risk of recurrence. </p> <p id="_3208" tabindex="-1">The randomized, open-label, multicenter <a href="/clinicaltrials/NCT01996267">TRAIN-2</a> trial (NCT01996267) evaluated the optimal chemotherapy backbone to use with neoadjuvant pertuzumab and trastuzumab in patients with stage II to stage III HER2-positive breast can
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      source file
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      source retrieved at
      2026-09-09T23:21:35.419733+00:00
      source string basis
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      source string sha256
      536430925e3b0008edd3fb69a869d5645bd6b6dc5c84c21ddf1b3e24f089874c
      source title
      Breast Cancer Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 25, 2025
        datetime
        2025-04-25T12:00:00Z
        display
        April 25, 2025

    Preserved source evidence · Not medical advice