Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study

Breast Cancer Clinical Trial

— TRAIN-3  

Official title:

Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03820063
• Other study ID #: BOOG 2018-01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 27, 2019
• Est. completion date: May 1, 2032

Study information

• Verified date: February 2023
• Source: Borstkanker Onderzoek Groep
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, single arm, phase II study evaluating the efficacy of image-guided de-escalating neoadjuvant treatment with paclitaxel, Herceptin® (trastuzumab), carboplatin, and pertuzumab (PTC-Ptz) in stage II-Ill HER2-positive breast cancer.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 462
• Est. completion date: May 1, 2032
• Est. primary completion date: November 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed primairy infiltrating breast cancer.

2. Stage II or Ill disease.

3. Overexpression and/or amplification of HER2 in an invasive component of the core biopsy.

4. Age <:18

5. ECOG Group performance status

6. LVEF >50% measured by echocardiography, MRI or MUGA

7. Known HR-status ( in percentages)

Exclusion Criteria:

1. Previous radiation therapy of chemotherapy

2. Pregnancy or breastfeeding

3. Evidence of distant metastases

4. Evidence of bilateral infiltrating breast cancer

5. Concurrent anti-cancer treatment or another investigational drug

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• PTC-Pz
Paclitaxel 80mg/m2 administered intravenously on day 1 and day 8 Herceptin® 6mg/kg administered intravenously on day 1 (loading dose 8mg/kg) or Herceptin® administered subcutaneously 600mg on day 1 Carboplatin AUC 6mg•ml/min administered intravenously on day 1 Pertuzumab 420mg administered intravenously on day 1 (loading dose 840mg) Treatment cycles are repeated on day 22 In case of non pCR; Adjuvant T-DM1, 3.6mg/kg Q 22 days, for 14 cycles.

Locations

Country	Name	City	State
Netherlands	Noordwest Ziekenhuisgroep	Alkmaar
Netherlands	Ziekenhuisgroep Twente	Almelo
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	Ziekenhuis Amstelland	Amstelveen
Netherlands	Amsterdam UMC	Amsterdam
Netherlands	NKI-AVL	Amsterdam
Netherlands	OLVG	Amsterdam
Netherlands	Gelre ziekenhuizen	Apeldoorn
Netherlands	Rijnstate	Arnhem
Netherlands	Rode Kruis Ziekenhuis	Beverwijk
Netherlands	Alexander Monro ziekenhuis	Bilthoven
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Reinier de Graaf Groep	Delft
Netherlands	Jeroen Bosch Ziekenhuis	Den Bosch
Netherlands	Haaglanden MC	Den Haag
Netherlands	Haga Ziekenhuis	Den Haag
Netherlands	Deventer ziekenhuis	Deventer
Netherlands	van Weel Bethesda	Dirksland
Netherlands	Nij Smellinghe	Drachten
Netherlands	Ziekenhuisvoorziening Gelderse Vallei	Ede
Netherlands	Catharina ziekenhuis	Eindhoven
Netherlands	Maxima Medisch Centrum	Eindhoven
Netherlands	Sint Annaziekenhuis	Geldrop
Netherlands	RIVAS Beatrixziekenhuis	Gorinchem
Netherlands	Groene Hart Ziekenhuis	Gouda
Netherlands	Martini ziekenhuis	Groningen
Netherlands	Ziekenhuis St. Jansdal	Harderwijk
Netherlands	Tjongerschans	Heerenveen
Netherlands	Zuyderland Medisch Centrum	Heerlen
Netherlands	Elkerliek ziekenhuis	Helmond
Netherlands	Tergooi	Hilversum
Netherlands	Spaarne Gasthuis	Hoofddorp
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	MUMC	Maastricht
Netherlands	Sint Antonius ziekenhuis	Nieuwegein
Netherlands	Canisius Wilhelmina Ziekenhuis	Nijmegen
Netherlands	Bernhoven	Oss
Netherlands	Stichting ziekenhuizen West-Friesland en Waterland	Purmerend
Netherlands	Laurentius ziekenhuis	Roermond
Netherlands	Erasmus MC, Universitair Medisch Centrum Rotterdam	Rotterdam
Netherlands	Franciscus Gasthuis en Vlietland	Rotterdam
Netherlands	Ikazia Ziekenhuis	Rotterdam
Netherlands	Maasstadziekenhuis	Rotterdam
Netherlands	ZorgSaam	Terneuzen
Netherlands	Rivierenland Ziekenhuis	Tiel
Netherlands	Elisabeth TweeSteden ziekenhuis	Tilburg
Netherlands	Diakonessenhuis Utrecht	Utrecht
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Netherlands	VieCurie Medisch Centrum voor Noord-Limburg	Venlo
Netherlands	SKB Ziekenhuis Winterswijk	Winterswijk
Netherlands	Zaans Medisch Centrum	Zaandam
Netherlands	Isala Klinieken	Zwolle

Sponsors (3)

Lead Sponsor	Collaborator
Borstkanker Onderzoek Groep	BOOG Study Center, Roche Pharma AG

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event free survival at three years	Number of patients without progression of disease recurrence, second primary or death	3 years
Secondary	Overall survival at three years	Number of patients alive at three years	3 years
Secondary	Pathologic complete response in breast and axilla	Number of patients with absence of invasive tumor cells in breast and axilla at surgery	an average of 6 months
Secondary	Radiologic complete response	Number of patients with absence of pathologic enhancement on MRI	an average of 6 months
Secondary	Number of neoadjuvant chemotherapy cycles administered	Number of neoadjuvant chemotherapy cycles administered per patient	an average of 1 year
Secondary	Number of radical and non-radical resections	Number of patients with radical and non-radical resections	an average of 6 months
Secondary	Incidence and severity of adverse events	Number of patients with toxicity grade >= 3 (CTCAE v5.0) until 30 days after last adjuvant administration	an average of 1 year
Secondary	Incidence and severity of cardiotoxicity and neuropathy	Number of patients with cardiotoxicity and neuropathy grade >= 2 (CTCAE v5.0) until 30 days after last adjuvant administration	an average of 1 year
Secondary	Incidence of symptomatic LVSD (heart failure),	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%	an average of 1 year
Secondary	Grade =3 laboratory test abnormalities	Number of patients with Grade =3 laboratory test abnormalities	an average of 1 year
Secondary	Incidence of number of tumor positive Vacuum Assisted Core Biopsy	Number of patients with tumor present at Vacuum Assisted Core Biopsy at the moment of radiological complete response on MRI	an average 6 months