Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2

Phase 3

Active, not recruiting

• Conditions: HER2 Positive; Breast Cancer
• Interventions: Drug: FEC-T+Pertuzumab; Drug: PTC+Pertuzumab

• Registration Number: NCT01996267
• Lead Sponsor: The Netherlands Cancer Institute

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.

Study Timeline

• Study First Submitted: 2013-11-18
• Study First Submitted QC: 2013-11-21
• Study First Posted: 2013-11-27
• Study Start: 2013-12
• Primary Completion: 2018-12
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-28
• Last Update Posted: 2024-03-29
• Study Completion: 2030-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 437

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FEC-T +Pertuzumab	FEC-T+Pertuzumab	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
PTC+Pertuzumab	PTC+Pertuzumab	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

Primary Outcome Measures

Name	Time	Method
Number of patients with pathological complete response	at week 30	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

Secondary Outcome Measures

Name	Time	Method
identify prognostic and predictive biomarkers for pCR	within one year after end of treatment	To identify prognostic and predictive biomarkers for pCR after neoadjuvant treatment
Number of patients with grade >2 adverse events as a measure of safety and tolerability	up to week 35	to describe the safety of the various regimens toxicity is compared between the two arms

Trial Locations

Locations (33)

Canisius-Wilhelmina Hospital; 🇳🇱 Nijmegen, Netherlands

MCA; 🇳🇱 Alkmaar, Netherlands

Rode Kruis Ziekenhuis; 🇳🇱 Beverwijk, Netherlands

Catharina Ziekenhuis; 🇳🇱 Eindhoven, Netherlands

Maxima Medisch Centrum; 🇳🇱 Eindhoven, Netherlands

Westfries Gasthuis; 🇳🇱 Hoorn, Netherlands

Isala Klinieken; 🇳🇱 Zwolle, Netherlands

AZVU; 🇳🇱 Amsterdam, Netherlands

OLVG; 🇳🇱 Amsterdam, Netherlands

Haga; 🇳🇱 Den Haag, Netherlands

Groene Hart; 🇳🇱 Gouda, Netherlands

LUMC; 🇳🇱 Leiden, Netherlands

Amphia ziekenhuis; 🇳🇱 Breda, Netherlands

Jeroen Bosch Hospital; 🇳🇱 Den Bosch, Netherlands

Deventer ziekenhuis; 🇳🇱 Deventer, Netherlands

Ziekenhuis Gelderse Vallei; 🇳🇱 Ede, Netherlands

ZGT; 🇳🇱 Almelo, Netherlands

VieCuri Medisch Centrum voor Noord-Limburg; 🇳🇱 Venlo, Netherlands

Zaans Medisch Centrum; 🇳🇱 Zaandam, Netherlands

Orbis Medisch Centrum; 🇳🇱 Geleen, Netherlands

Kennemer Gasthuis; 🇳🇱 Haarlem, Netherlands

Atrium Medisch Centrum Parkstad; 🇳🇱 Heerlen, Netherlands

MCL; 🇳🇱 Leeuwarden, Netherlands

Diaconessenhuis Meppel; 🇳🇱 Meppel, Netherlands

Vlietland Ziekenhuis; 🇳🇱 Schiedam, Netherlands

Antoni van Leeuwenhoek; 🇳🇱 Amsterdam, Netherlands

St Anna Geldrop; 🇳🇱 Geldrop, Netherlands

Waterlandziekenhuis; 🇳🇱 Purmerend, Netherlands

St. Elisabeth; 🇳🇱 Tilburg, Netherlands

Diaconessenhuis Utrecht; 🇳🇱 Utrecht, Netherlands

Reinier de Graaf Groep; 🇳🇱 Delft, Netherlands

Bronovo Ziekenhuis; 🇳🇱 den Haag, Netherlands

Spaarne ziekenhuis; 🇳🇱 Hoofddorp, Netherlands