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

Phase 2

Completed

• Conditions: Breast Cancer; HER2 Positive
• Interventions: Drug: paclitaxel, trastuzumab and carboplatin

• Registration Number: NCT00768859
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09
• Study First Submitted: 2008-10-07
• Study First Submitted QC: 2008-10-07
• Study First Posted: 2008-10-08
• Primary Completion: 2011-08
• Status Verified: 2012-05
• Study Completion: 2012-05
• Last Update Submitted: 2012-05-10
• Last Update Posted: 2012-05-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 111

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	paclitaxel, trastuzumab and carboplatin	paclitaxel, trastuzumab and carboplatin

Primary Outcome Measures

Name	Time	Method
Pathologic complete response (pCR) rate at surgery	at the completion of neo-adjuvant chemotherapy

Secondary Outcome Measures

Name	Time	Method
To describe disease-free and overall survival	during routine follow up visits after surgery

Trial Locations

Locations (9)

Medisch Centrum Alkmaar; 🇳🇱 Alkmaar, Netherlands

NKI-AVL; 🇳🇱 Amsterdam, Netherlands

Onze Lieve Vrouwe Gasthuis; 🇳🇱 Amsterdam, Netherlands

Catharina Ziekenhuis; 🇳🇱 Eindhoven, Netherlands

Kennemer Gasthuis; 🇳🇱 Haarlem, Netherlands

Leids Universitair Medisch centrum; 🇳🇱 Leiden, Netherlands

Medisch Centrum Haaglanden; 🇳🇱 Leidschendam, Netherlands

Sint Antonius Ziekenhuis; 🇳🇱 Nieuwegein, Netherlands

Reinier de Graaf Gasthuis; 🇳🇱 Delft, Netherlands