Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2

Breast Cancer Clinical Trial

— TRAIN-2  

Official title:

Optimizing Neoadjuvant Systemic Treatment for HER2 Positive Breast Cancer - the TRAIN-2 Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01996267
• Other study ID #: M13TRT
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 2013
• Est. completion date: December 2030

Study information

• Verified date: March 2024
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 437
• Est. completion date: December 2030
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• HER2 Positive

Intervention

Drug:
• PTC+Pertuzumab
Cycle repeated every 21 days
• FEC-T+Pertuzumab
Cycle is repeated every 21 days

Locations

Country	Name	City	State
Netherlands	MCA	Alkmaar
Netherlands	ZGT	Almelo
Netherlands	Antoni van Leeuwenhoek	Amsterdam
Netherlands	AZVU	Amsterdam
Netherlands	OLVG	Amsterdam
Netherlands	Rode Kruis Ziekenhuis	Beverwijk
Netherlands	Amphia ziekenhuis	Breda
Netherlands	Reinier de Graaf Groep	Delft
Netherlands	Jeroen Bosch Hospital	Den Bosch
Netherlands	Bronovo Ziekenhuis	den Haag
Netherlands	Haga	Den Haag
Netherlands	Deventer ziekenhuis	Deventer
Netherlands	Ziekenhuis Gelderse Vallei	Ede
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Maxima Medisch Centrum	Eindhoven
Netherlands	St Anna Geldrop	Geldrop
Netherlands	Orbis Medisch Centrum	Geleen
Netherlands	Groene Hart	Gouda
Netherlands	Kennemer Gasthuis	Haarlem
Netherlands	Atrium Medisch Centrum Parkstad	Heerlen
Netherlands	Spaarne ziekenhuis	Hoofddorp
Netherlands	Westfries Gasthuis	Hoorn
Netherlands	MCL	Leeuwarden
Netherlands	LUMC	Leiden
Netherlands	Diaconessenhuis Meppel	Meppel
Netherlands	Canisius-Wilhelmina Hospital	Nijmegen
Netherlands	Waterlandziekenhuis	Purmerend
Netherlands	Vlietland Ziekenhuis	Schiedam
Netherlands	St. Elisabeth	Tilburg
Netherlands	Diaconessenhuis Utrecht	Utrecht
Netherlands	VieCuri Medisch Centrum voor Noord-Limburg	Venlo
Netherlands	Zaans Medisch Centrum	Zaandam
Netherlands	Isala Klinieken	Zwolle

Sponsors (3)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute	Borstkanker Onderzoek Groep, Roche Pharma AG

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with pathological complete response	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	at week 30
Secondary	Number of patients with grade >2 adverse events as a measure of safety and tolerability	to describe the safety of the various regimens toxicity is compared between the two arms	up to week 35
Secondary	identify prognostic and predictive biomarkers for pCR	To identify prognostic and predictive biomarkers for pCR after neoadjuvant treatment	within one year after end of treatment