Reducing the number chemotherapy cycles based on radiologic tumor response in HER2-positive breast cancer: the TRAIN-3 study (BOOG 2018-01)

Image-guided de-escalation of neoadjuvant chemotherapy in HER2-positive breast cancer: the TRAIN-3 study - TRAIN-3

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-003275-35-NL

Enrollment

462

Registered

2019-01-08

Start date

2019-02-07

Completion date

Unknown

Last updated

2019-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HER2-positive, stage II/III breast cancer MedDRA version: 20.0 Level: PT Classification code 10006200 Term: Breast cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10006201 Term: Breast cancer stage III System Organ Clas

Interventions

Trade Name: Herceptin Product Name: Herceptin Pharmaceutical Form: Concentrate for solution for injection/infusion INN or Proposed INN: TRASTUZUMAB

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Histologically confirmed infiltrating breast cancer. 2. Stage II or III disease. 3. Overexpression and/or amplification of HER2 in an invasive component of the core biopsy. 4. Age 50% measured by echocardiography, MRI or MUGA 7. Known HR-status ( in percentages) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 462 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 462

Exclusion criteria

Exclusion criteria: 1. Previous chemotherapy 2. Pregnancy or breastfeeding 3. Evidence of distant metastases 4. Evidence of bilateraal infiltrating breast cancer 5. Concurrent anti-cancer treatment or another investigational drug

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate efficacy of image-guided de-escalating chemotherapy in the presence of dual HER2-blockade with Herceptin® and pertuzumab in HER2-positive breast cancer, as measured by three-year event-free survival.; Secondary Objective: Secondary efficacy objectives -To evaluate 3-year overall survival -To evaluate pCR rate in breast and axilla -To evaluate 5-year, and 10-year overall and event-free survival rate -To evaluate the association between pCR and long-term outcome -To evaluate the association between radiologic complete response (rCR) and pCR -To compare short-term and long-term efficacy by number of chemotherapy cycles received -To compare non-radical resection percentages between rCR and no rCR Safety objectives -Incidence and severity of adverse events grade =3 (CTCAE v5.0) -Incidence and severity of cardiotoxicity and neuropathy grade =2 -Incidence of symptomatic LVSD (heart failure), and incidence of asymptomatic decrease in LVEF, defined as an asymptomatic decline in LVEF requiring treatment or leading to discontinuation of pertuzumab and Herceptin®, or a decrease of =10 percentage points from baseline to an LVEF of <50% -Grade =3 laboratory test abnormalities ; Primary end point(s): Primary endpoint: Event-free survival (EFS), defined as the interval from registration to the earliest occurrence of disease progression resulting in inoperability, invasive loco regional recurrence, distant metastases, or death from any cause, whichever comes first. ; Timepoint(s) of evaluation of this end point: Interim analysis: 150 patient years Final analysis: 700 patient years	—

Measure

Time frame

Main Objective: To evaluate efficacy of image-guided de-escalating chemotherapy in the presence of dual HER2-blockade with Herceptin® and pertuzumab in HER2-positive breast cancer, as measured by three-year event-free survival.; Secondary Objective: Secondary efficacy objectives -To evaluate 3-year overall survival -To evaluate pCR rate in breast and axilla -To evaluate 5-year, and 10-year overall and event-free survival rate -To evaluate the association between pCR and long-term outcome -To evaluate the association between radiologic complete response (rCR) and pCR -To compare short-term and long-term efficacy by number of chemotherapy cycles received -To compare non-radical resection percentages between rCR and no rCR Safety objectives -Incidence and severity of adverse events grade =3 (CTCAE v5.0) -Incidence and severity of cardiotoxicity and neuropathy grade =2 -Incidence of symptomatic LVSD (heart failure), and incidence of asymptomatic decrease in LVEF, defined as an asymptomatic decline in LVEF requiring treatment or leading to discontinuation of pertuzumab and Herceptin®, or a decrease of =10 percentage points from baseline to an LVEF of <50% -Grade =3 laboratory test abnormalities ; Primary end point(s): Primary endpoint: Event-free survival (EFS), defined as the interval from registration to the earliest occurrence of disease progression resulting in inoperability, invasive loco regional recurrence, distant metastases, or death from any cause, whichever comes first. ; Timepoint(s) of evaluation of this end point: Interim analysis: 150 patient years Final analysis: 700 patient years

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Secondary

Measure	Time frame
Secondary end point(s): • Overall survival (OS), defined as the time from registration to death from any cause • Pathologic complete response in breast and axilla, defined as the absence of invasive tumor cells, irrespective of the presence of in-situ lesions • Radiologic complete response defined as the absence of pathologic enhancement on MRI and normalization of possible lymph node involvement at ultrasound and FNA examination • Number of neoadjuvant chemotherapy cycles administered • Number of radical and non-radical resections • Incidence and severity of adverse events grade =3 (CTCAE v5.0) until 30 days after last treatment administration (adjuvant) • Incidence and severity of cardiotoxicity and neuropathy grade =2 • Incidence of symptomatic LVSD (heart failure), and incidence of asymptomatic decrease in LVEF, defined as an asymptomatic decline in LVEF requiring treatment or leading to discontinuation of pertuzumab and Herceptin, or a decrease of =10 percentage points from baseline to an LVEF of <50% • Grade =3 laboratory test abnormalities ;Timepoint(s) of evaluation of this end point: At final analysis, 5 and 10-year follow-up.	—

Measure

Time frame

Secondary end point(s): • Overall survival (OS), defined as the time from registration to death from any cause • Pathologic complete response in breast and axilla, defined as the absence of invasive tumor cells, irrespective of the presence of in-situ lesions • Radiologic complete response defined as the absence of pathologic enhancement on MRI and normalization of possible lymph node involvement at ultrasound and FNA examination • Number of neoadjuvant chemotherapy cycles administered • Number of radical and non-radical resections • Incidence and severity of adverse events grade =3 (CTCAE v5.0) until 30 days after last treatment administration (adjuvant) • Incidence and severity of cardiotoxicity and neuropathy grade =2 • Incidence of symptomatic LVSD (heart failure), and incidence of asymptomatic decrease in LVEF, defined as an asymptomatic decline in LVEF requiring treatment or leading to discontinuation of pertuzumab and Herceptin, or a decrease of =10 percentage points from baseline to an LVEF of <50% • Grade =3 laboratory test abnormalities ;Timepoint(s) of evaluation of this end point: At final analysis, 5 and 10-year follow-up.

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Countries

Netherlands

Contacts

Public ContactPrincipal Investigator

Netherlands Cancer Institue

a.vd.voort@nki.nl0031205129111

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026