Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study (TRAIN-3)
Study Overview
Detailed Description
High pathological complete response (pCR)-rates are seen using different neoadjuvant chemotherapy schedules with trastuzumab and pertuzumab in HER2-positive stage II - III breast cancer patients. Total pCR rates in breast and axilla have been described as high as 64%, and with an even higher rate of >80% in patients with HER2-positive and hormone receptor (HR) negative tumors. PCR is associated with better long-term outcomes in patients with HER2-positive breast cancer. Three year progression-free survival ranges between 85-90%. Neoadjuvant treatment of HER2-positive breast cancer typically consists of six to nine cycles of treatment. Longer duration of treatment is associated with higher pCR-rates but gives more toxicity. Pathological complete responses are sometimes seen after only 10-12 days of neoadjuvant treatment. It is therefore important to investigate which patients can safely be treated with less than six cycles of chemotherapy and who requires more than six cycles for maximum activity.
The radiologic response of a breast tumor after neoadjuvant therapy is predictive of the pathologic response, although the accuracy differs between breast cancer subtypes. It is hypothesized that patients with an early complete radiologic response may not benefit from additional chemotherapy and can be referred for early surgery. Patients who have not achieved pCR after early surgery despite radiologic complete response (rCR) are candidates for further adjuvant chemotherapy to complete the initially planned number of treatment cycles and maintain maximum treatment activity. Imaged guided de-escalation in which the number of treatment cycles is determined by the radiologic response could thus reduce toxicity in neoadjuvant treatment while maintaining activity.
This study will evaluate the efficacy of image-guided de-escalation of neoadjuvant chemotherapy in patients with HER2-positive breast cancer.
To maintain efficacy, patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1. Patients who achieve early pCR will continue treatment with Herceptin® and pertuzumab to complete one full year of treatment.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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's-Hertogenbosch, Netherlands
- Jeroen Bosch Ziekenhuis
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Alkmaar, Netherlands
- Noordwest Ziekenhuisgroep
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Almelo, Netherlands
- Ziekenhuisgroep Twente
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Amersfoort, Netherlands
- Meander Medisch Centrum
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Amstelveen, Netherlands
- Ziekenhuis Amstelland
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Amsterdam, Netherlands
- OLVG
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Amsterdam, Netherlands
- Amsterdam UMC
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Amsterdam, Netherlands
- NKI-AVL
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Apeldoorn, Netherlands
- Gelre Ziekenhuizen
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Arnhem, Netherlands
- Rijnstate
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Beverwijk, Netherlands
- Rode Kruis Ziekenhuis
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Bilthoven, Netherlands
- Alexander Monro Ziekenhuis
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Breda, Netherlands
- Amphia Ziekenhuis
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Delft, Netherlands
- Reinier de Graaf Groep
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Deventer, Netherlands
- Deventer Ziekenhuis
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Dirksland, Netherlands
- Van Weel Bethesda
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Drachten, Netherlands
- Nij Smellinghe
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Ede, Netherlands
- Ziekenhuisvoorziening Gelderse Vallei
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Eindhoven, Netherlands
- Catharina Ziekenhuis
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Eindhoven, Netherlands
- Maxima Medisch Centrum
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Geldrop, Netherlands
- Sint Annaziekenhuis
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Gorinchem, Netherlands
- Rivas Beatrixziekenhuis
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Gouda, Netherlands
- Groene Hart Ziekenhuis
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Groningen, Netherlands
- Martini Ziekenhuis
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Harderwijk, Netherlands
- Ziekenhuis St. Jansdal
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Heerenveen, Netherlands
- Tjongerschans
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Heerlen, Netherlands
- Zuyderland Medisch Centrum
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Helmond, Netherlands
- Elkerliek Ziekenhuis
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Hilversum, Netherlands
- Tergooi
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Hoofddorp, Netherlands
- Spaarne Gasthuis
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Leeuwarden, Netherlands
- Medisch Centrum Leeuwarden
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Maastricht, Netherlands
- MUMC
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Nieuwegein, Netherlands
- Sint Antonius Ziekenhuis
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Nijmegen, Netherlands
- Canisius Wilhelmina Ziekenhuis
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Oss, Netherlands
- Bernhoven
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Purmerend, Netherlands
- Stichting ziekenhuizen West-Friesland en Waterland
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Roermond, Netherlands
- Laurentius ziekenhuis
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Rotterdam, Netherlands
- Franciscus Gasthuis en Vlietland
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Rotterdam, Netherlands
- Erasmus MC, Universitair Medisch Centrum Rotterdam
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Rotterdam, Netherlands
- Ikazia Ziekenhuis
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Rotterdam, Netherlands
- Maasstadziekenhuis
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Terneuzen, Netherlands
- ZorgSaam
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The Hague, Netherlands
- Haga Ziekenhuis
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The Hague, Netherlands
- Haaglanden MC
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Tiel, Netherlands
- Rivierenland Ziekenhuis
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Tilburg, Netherlands
- Elisabeth Tweesteden Ziekenhuis
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Utrecht, Netherlands
- Diakonessenhuis Utrecht
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Utrecht, Netherlands
- Universitair Medisch Centrum Utrecht
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Venlo, Netherlands
- VieCurie Medisch Centrum voor Noord-Limburg
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Winterswijk, Netherlands
- SKB Ziekenhuis Winterswijk
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Zaandam, Netherlands
- Zaans Medisch Centrum
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Zwolle, Netherlands
- Isala Klinieken
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologically confirmed primairy infiltrating breast cancer.
- Stage II or Ill disease.
- Overexpression and/or amplification of HER2 in an invasive component of the core biopsy.
- Age <:18
- ECOG Group performance status
- LVEF >50% measured by echocardiography, MRI or MUGA
- Known HR-status ( in percentages)
Exclusion Criteria:
- Previous radiation therapy of chemotherapy
- Pregnancy or breastfeeding
- Evidence of distant metastases
- Evidence of bilateral infiltrating breast cancer
- Concurrent anti-cancer treatment or another investigational drug
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: PTC-Pz
Patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1. |
In case of non pCR; Adjuvant T-DM1, 3.6mg/kg Q 22 days, for 14 cycles. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Event free survival at three years
Time Frame: 3 years
|
Number of patients without progression of disease recurrence, second primary or death
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3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall survival at three years
Time Frame: 3 years
|
Number of patients alive at three years
|
3 years
|
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Pathologic complete response in breast and axilla
Time Frame: an average of 6 months
|
Number of patients with absence of invasive tumor cells in breast and axilla at surgery
|
an average of 6 months
|
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Radiologic complete response
Time Frame: an average of 6 months
|
Number of patients with absence of pathologic enhancement on MRI
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an average of 6 months
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Number of neoadjuvant chemotherapy cycles administered
Time Frame: an average of 1 year
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Number of neoadjuvant chemotherapy cycles administered per patient
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an average of 1 year
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Number of radical and non-radical resections
Time Frame: an average of 6 months
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Number of patients with radical and non-radical resections
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an average of 6 months
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Incidence and severity of adverse events
Time Frame: an average of 1 year
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Number of patients with toxicity grade >= 3 (CTCAE v5.0) until 30 days after last adjuvant administration
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an average of 1 year
|
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Incidence and severity of cardiotoxicity and neuropathy
Time Frame: an average of 1 year
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Number of patients with cardiotoxicity and neuropathy grade >= 2 (CTCAE v5.0) until 30 days after last adjuvant administration
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an average of 1 year
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Incidence of symptomatic LVSD (heart failure),
Time Frame: an average of 1 year
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Number of patients with an asymptomatic decline in LVEF requiring treatment or leading to discontinuation of pertuzumab and Herceptin, or a decrease ≥10 percentage points from baseline to a LVEF <50%
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an average of 1 year
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Grade ≥3 laboratory test abnormalities
Time Frame: an average of 1 year
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Number of patients with Grade ≥3 laboratory test abnormalities
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an average of 1 year
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Incidence of number of tumor positive Vacuum Assisted Core Biopsy
Time Frame: an average 6 months
|
Number of patients with tumor present at Vacuum Assisted Core Biopsy at the moment of radiological complete response on MRI
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an average 6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: G S Sonke, MD, NKI-AVL
- Study Director: A E van Leeuwen- Stok, PhD, BOOG Study Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BOOG 2018-01
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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