Neoadjuvant Chemotherapy in HER2 Positive Breast Cancer, TRAIN-2

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by The Netherlands Cancer Institute
Sponsor:
Collaborators:
Roche Pharma AG
Borstkanker Onderzoek Groep
Information provided by (Responsible Party):
The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:
NCT01996267
First received: November 18, 2013
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Breast Cancer
HER2 Positive
Drug: PTC+Pertuzumab
Drug: FEC-T+Pertuzumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Optimizing Neoadjuvant Systemic Treatment for HER2 Positive Breast Cancer - the TRAIN-2 Study

Resource links provided by NLM:


Further study details as provided by The Netherlands Cancer Institute:

Primary Outcome Measures:
  • Number of patients with pathological complete response [ Time Frame: at week 30 ] [ Designated as safety issue: No ]
    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:
  • Number of patients with grade >2 adverse events as a measure of safety and tolerability [ Time Frame: up to week 35 ] [ Designated as safety issue: Yes ]
    to describe the safety of the various regimens toxicity is compared between the two arms

  • identify prognostic and predictive biomarkers for pCR [ Time Frame: within one year after end of treatment ] [ Designated as safety issue: No ]
    To identify prognostic and predictive biomarkers for pCR after neoadjuvant treatment


Estimated Enrollment: 437
Study Start Date: December 2013
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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
Drug: FEC-T+Pertuzumab
Other Names:
  • 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
Active Comparator: 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
Drug: PTC+Pertuzumab
Other Names:
  • 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01996267

Contacts
Contact: Mette S van Ramshorst, MD +3120512 ext 6169 m.v.ramshorst@nki.nl
Contact: Gabe S Sonke, MD +3120512 ext 2951 g.sonke@nki.nl

Locations
Netherlands
MCA Not yet recruiting
Alkmaar, Netherlands, 1815 JD
Contact: S Vrijaldenhoven, MD         
Principal Investigator: S Vrijaldenhoven, MD         
ZGT Not yet recruiting
Almelo, Netherlands, 7609 PP
Contact: I M Oving, MD       i.oving@zgt.nl   
Principal Investigator: I M Oving, MD         
Antoni van Leeuwenhoek Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Gabe S Sonke, MD    +3120512 ext 2951    g.sonke@nki.nl   
Contact: Mette S van Ramshorst, M    +3120512 ext 6196    m.v.ramshorst@nki.nl   
Principal Investigator: Gabe S Sonke, MD         
OLVG Not yet recruiting
Amsterdam, Netherlands, 1090 HM
Contact: J M Meerum Terwogt, MD         
Principal Investigator: J M Meerum Terwogt, MD         
AZVU Active, not recruiting
Amsterdam, Netherlands, 1081 HV
Rode Kruis Ziekenhuis Not yet recruiting
Beverwijk, Netherlands, 1940 EB
Contact: A N Goosens, MD       agoosens@rkz.nl   
Principal Investigator: A N Goosens, MD         
Amphia ziekenhuis Not yet recruiting
Breda, Netherlands, 4819 EV
Contact: J B Heijns, MD       JHeijns@amphia.nl   
Principal Investigator: J B Heijns, MD         
Reinier de Graaf Groep Recruiting
Delft, Netherlands, 2625 AD
Contact: V O Dezentje, MD         
Principal Investigator: V O Dezentje, MD         
Jeroen Bosch Hospital Not yet recruiting
Den Bosch, Netherlands
Contact: T. Smilde, MD, PhD         
Principal Investigator: T. Smilde, MD, PhD         
Bronovo Ziekenhuis Active, not recruiting
den Haag, Netherlands, 2597 AX
Haga Recruiting
Den Haag, Netherlands, 2545 CH
Contact: J E Portielje, MD       j.portielje@hagaziekenhuis.nl   
Principal Investigator: J E Portielje, MD         
Deventer ziekenhuis Recruiting
Deventer, Netherlands, 7416 SE
Contact: A L Imholz, MD       imholza@dz.nl   
Principal Investigator: A L Imholz, MD         
Ziekenhuis Gelderse Vallei Not yet recruiting
Ede, Netherlands, 6716 RP
Contact: A W Haringhuizen, MD       haringhuizena@zgv.nl   
Principal Investigator: A W Haringhuizen, MD         
Maxima Medisch Centrum Not yet recruiting
Eindhoven, Netherlands, 5631 BM
Contact: L W Tick, MD         
Principal Investigator: L W Tick, MD         
Catharina Ziekenhuis Active, not recruiting
Eindhoven, Netherlands, 5602 ZA
St Anna Geldrop Not yet recruiting
Geldrop, Netherlands, 5664 EH
Contact: A Smals, MD       a.smals@st-anna.nl   
Principal Investigator: A Smals, MD         
Orbis Medisch Centrum Active, not recruiting
Geleen, Netherlands, 6162 BG
Groene Hart Not yet recruiting
Gouda, Netherlands, 2803 HH
Contact: B C Tanis, MD       bea.tanis@ghz.nl   
Principal Investigator: B C Tanis, MD         
Kennemer Gasthuis Active, not recruiting
Haarlem, Netherlands, 2035 RC
Atrium Medisch Centrum Parkstad Not yet recruiting
Heerlen, Netherlands, 6401 CX
Contact: F van de Berkmortel, MD         
Principal Investigator: F van de Berkmortel, MD         
Spaarne ziekenhuis Recruiting
Hoofddorp, Netherlands, 2134 TM
Contact: B de Valk, MD       bdevalk@spaarneziekenhuis.nl   
Principal Investigator: B de Valk, MD         
Westfries Gasthuis Not yet recruiting
Hoorn, Netherlands, 1624 NP
Contact: S M van den Heiligenberg, MD       s.m.vandenheiligenberg@westfriesgasthuis.nl   
Principal Investigator: S M van den Heiligenberg, MD         
MCL Not yet recruiting
Leeuwarden, Netherlands, 8934 AD
Contact: H de Graaf, MD       graafhi@znb.nl   
Principal Investigator: H de Graaf, MD         
LUMC Active, not recruiting
Leiden, Netherlands, 2300 RC
Diaconessenhuis Meppel Active, not recruiting
Meppel, Netherlands, 7943 KA
Canisius-Wilhelmina Hospital Not yet recruiting
Nijmegen, Netherlands
Contact: C.M.P.W. Mandigers, MD, PhD         
Principal Investigator: C.M.P.W. Mandigers, MD, PhD         
Waterlandziekenhuis Not yet recruiting
Purmerend, Netherlands, 1441 RN
Contact: Brakenhoff, MD       brakenhoff@wlz.nl   
Principal Investigator: Brakenhoff, MD         
Vlietland Ziekenhuis Not yet recruiting
Schiedam, Netherlands, 3100 AE
Contact: Q C van Rossum-Schornagel, MD         
Principal Investigator: Q C van Rossum-Schornagel, MD         
St. Elisabeth Not yet recruiting
Tilburg, Netherlands, 5022 GC
Contact: J M van Riel, MD       jmgriel@elisabeth.nl   
Principal Investigator: J M van Riel, MD         
Diaconessenhuis Utrecht Not yet recruiting
Utrecht, Netherlands, 3582 KE
Contact: D ten Bokkel Huinink, MD       dtbokkel@diakhuis.nl   
Principal Investigator: D ten Bokkel Huinink, MD         
VieCuri Medisch Centrum voor Noord-Limburg Active, not recruiting
Venlo, Netherlands
Zaans Medisch Centrum Not yet recruiting
Zaandam, Netherlands, 1502 DV
Contact: S Bakker, MD       bakker.sd@zaansmc.nl   
Principal Investigator: S Bakker, MD         
Isala Klinieken Recruiting
Zwolle, Netherlands, 8025 AB
Contact: A H. Honkoop, MD       a.h.honkoop@isala.nl   
Principal Investigator: A H Honkoop, MD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Roche Pharma AG
Borstkanker Onderzoek Groep
Investigators
Principal Investigator: Gabe S Sonke, MD Antoni van Leeuwenhoek, Amsterdam
  More Information

No publications provided

Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT01996267     History of Changes
Other Study ID Numbers: M13TRT
Study First Received: November 18, 2013
Last Updated: May 22, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by The Netherlands Cancer Institute:
neoadjuvant
breast cancer
HER2 positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Trastuzumab
Pertuzumab
Carboplatin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on August 01, 2014