Trastuzumab in a Neo-adjuvant Regimen for HER2+ Breast Cancer - the TRAIN Study (TRAIN)

To determine the activity of the combination of paclitaxel, trastuzumab and carboplatin as neo-adjuvant treatment in patients with stage II or III HER2 positive breast cancer

Study Overview

• Status: Completed
• Conditions: Breast Cancer; HER2 Positive
• Intervention / Treatment: Drug: paclitaxel, trastuzumab and carboplatin

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Alkmaar, Netherlands, 1800 AM
    • Medisch Centrum Alkmaar
  • Amsterdam, Netherlands, 1091 HA
    • Onze Lieve Vrouwe Gasthuis
  • Amsterdam, Netherlands, 1066 CX
    • NKI-AVL
  • Delft, Netherlands, 2600 AG
    • Reinier de Graaf Gasthuis
  • Eindhoven, Netherlands, 5602 ZA
    • Catharina Ziekenhuis
  • Haarlem, Netherlands, 2035 RC
    • Kennemer Gasthuis
  • Leiden, Netherlands, 2300 RC
    • Leids Universitair Medisch Centrum
  • Leidschendam, Netherlands, 2262 BA
    • Medisch Centrum Haaglanden
  • Nieuwegein, Netherlands, 3430 EM
    • Sint Antonius Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed infiltrating breast cancer.
• Stage II or stage III breast cancer.28 'Locally advanced breast cancer' patients are consequently eligible, including those with ipsilateral supraclavicular lymph node metastases. N1 status must have been demonstrated by either fine needle aspiration from an axillary lymph node or by a metastasis of >2 mm in diameter at sentinel node biopsy. Stage IIA patients are eligible if the tumor is >3 cm in diameter or if the tumor is between 2 and 3 cm in diameter but a breast conserving surgery is not possible.

• Overexpression and/or amplification of HER2 in an invasive component of the core biopsy, according to one of the following definitions:

  • >10% of invasive tumor cells showing strong complete circumferential membrane staining (score 3+)
  • >10% of invasive tumor cells showing moderate complete circumferential membrane staining (score 2+) and demonstrating HER2 gene amplification defined as a FISH ratio of HER2 gene copies to chromosome 17 signals of >2.2. or as >5 HER2 gene copies per nucleus in CISH analysis.

Patients with a negative or equivocal overall result (FISH test ratio of <2.2, <6.0 HER2 gene copies per nucleus) and staining scores of 0,1+, 2+ or 3+ (in 30% or less neoplastic cells) by IHC are not eligible for participation in the trial.

• Age ≥18
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (Appendix B)
• Adequate bone marrow function (ANC >1.0 x 109/l, platelets >100 x 109/l)
• Adequate hepatic function (ALAT, ASAT and bilirubin <2 times upper limit of normal)
• Adequate renal function (creatinine clearance >60 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
• Signed written informed consent

Exclusion Criteria:

• No previous radiation therapy or chemotherapy
• No 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.
• No current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection.
• No evidence of distant metastases. Staging examinations must have included a chest radiograph, an ultrasound examination of the liver and an isotope bone scan. Abnormal uptake on the isotope bone scan can only be accepted if MRI, CT-scan, or plain radiograph excludes bone metastases.
• No concurrent anti-cancer treatment or another investigational drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; paclitaxel, trastuzumab and carboplatin	Drug: paclitaxel, trastuzumab and carboplatin; paclitaxel; 70 mg/m2 trastuzumab; 2 mg/kg (loading dose 4 mg/kg) carboplatin; AUC = 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathologic complete response (pCR) rate at surgery	at the completion of neo-adjuvant chemotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
To describe disease-free and overall survival	during routine follow up visits after surgery

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Investigators: Principal Investigator: G S Sonke, MD, NKI-AVL

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: October 7, 2008
• First Submitted That Met QC Criteria: October 7, 2008
• First Posted (Estimate): October 8, 2008

Study Record Updates

• Last Update Posted (Estimate): May 11, 2012
• Last Update Submitted That Met QC Criteria: May 10, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: breast cancer; paclitaxel; carboplatin; trastuzumab; HER2 positive; neo-adjuvant
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Carboplatin; Paclitaxel; Trastuzumab
• Other Study ID Numbers: M08TRA; 2008-000987-18 (EudraCT Number)