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

Sponsor

The Netherlands Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00768859

Collaborator

(none)

111

Enrollment

Locations

Arm

Duration (Months)

12.3

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer HER2 Positive	Drug: paclitaxel, trastuzumab and carboplatin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

111 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2008

Actual Primary Completion Date :

Aug 1, 2011

Actual Study Completion Date :

May 1, 2012

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Pathologic complete response (pCR) rate at surgery [at the completion of neo-adjuvant chemotherapy]

Secondary Outcome Measures

To describe disease-free and overall survival [during routine follow up visits after surgery]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Medisch Centrum Alkmaar	Alkmaar	Netherlands	1800 AM
2	NKI-AVL	Amsterdam	Netherlands	1066 CX
3	Onze Lieve Vrouwe Gasthuis	Amsterdam	Netherlands	1091 HA
4	Reinier de Graaf Gasthuis	Delft	Netherlands	2600 AG
5	Catharina Ziekenhuis	Eindhoven	Netherlands	5602 ZA
6	Kennemer Gasthuis	Haarlem	Netherlands	2035 RC
7	Leids Universitair Medisch centrum	Leiden	Netherlands	2300 RC
8	Medisch Centrum Haaglanden	Leidschendam	Netherlands	2262 BA
9	Sint Antonius Ziekenhuis	Nieuwegein	Netherlands	3430 EM