Clinical trial NCT00768859: Trastuzumab in a Neo-adjuvant Regimen for HER2+ Breast Cancer - the TRAIN Study
Official title: Trastuzumab in a Neo-adjuvant Regimen for HER2+ Breast Cancer - the TRAIN Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
HER2 Positive
Keywords: breast cancer
HER2 positive
neo-adjuvant
trastuzumab
paclitaxel
carboplatin
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
First posted: 2008-10-08
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Pathologic complete response (pCR) rate at surgery
timeFrame: at the completion of neo-adjuvant chemotherapy
Secondary outcomes:
measure: To describe disease-free and overall survival
timeFrame: during routine follow up visits after surgery
Other outcomes:
Locations:
city: Alkmaar
country: Netherlands
facility: Medisch Centrum Alkmaar
city: Amsterdam
country: Netherlands
facility: NKI-AVL
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Haarlem
country: Netherlands
facility: Kennemer Gasthuis
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch centrum
city: Leidschendam
country: Netherlands
facility: Medisch Centrum Haaglanden
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis
Study officials:
affiliation: NKI-AvL
name: G S Sonke, MD
role: PRINCIPAL_INVESTIGATOR
References: