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

Breast Cancer Clinical Trial

— TRAIN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00768859
• Other study ID #: M08TRA
• Secondary ID: 2008-000987-18
• Status: Completed
• Phase: Phase 2
• First received: October 7, 2008
• Last updated: May 10, 2012
• Start date: September 2008
• Est. completion date: May 2012

Study information

• Verified date: May 2012
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: May 2012
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• HER2 Positive

Intervention

Drug:
• paclitaxel, trastuzumab and carboplatin
paclitaxel; 70 mg/m2 trastuzumab; 2 mg/kg (loading dose 4 mg/kg) carboplatin; AUC = 3

Locations

Country	Name	City	State
Netherlands	Medisch Centrum Alkmaar	Alkmaar
Netherlands	NKI-AVL	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Reinier de Graaf Gasthuis	Delft
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Kennemer Gasthuis	Haarlem
Netherlands	Leids Universitair Medisch centrum	Leiden
Netherlands	Medisch Centrum Haaglanden	Leidschendam
Netherlands	Sint Antonius Ziekenhuis	Nieuwegein

Sponsors (1)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic complete response (pCR) rate at surgery		at the completion of neo-adjuvant chemotherapy	No
Secondary	To describe disease-free and overall survival		during routine follow up visits after surgery	No