Early phase Clinical trial, Randomized Study of T DM1 versus T DM1 plus docetaxel in first line treatment for locally advanced or metastatic HER2+ breast cancer.

• Conditions: Progressive or recurrent, locally advanced unresectable or metastatic HER2+ breast carcinoma in patients who have not received previous chemotherapy for the advanced disease.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-000793-19-ES
• Lead Sponsor: SOLTI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-08-06
• Last Update Posted: 27 October 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

1.Written Informed Consent for all study procedures in accordance with the local regulatory requirements prior to starting any Protocol specific procedures.
2.To provide tumor tissue or to have the possibility to collect newly tumor sample from the patient to be able to perform PAM50 analysis. The minimum conditions to achieve this are 1) presence of at least 1 tumor core with a minimum tissue area of 10mm2, 2) with at least 35% of tumoral cells and 3) enough tissue to perform at least 3 sections of 10 ?m each.
3.Women.
4.Age ? 18 years.
5.ECOG performance status of 0 or 1.
6.Invasive HER2+ breast cancer assessed centrally, defined by the clinical guidelines of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) (Wolff JCO 2013):
a)IHC 3+ overexpression (circumferential membrane staining that is complete, intense, observed in >10% of the invasive tumor cells)
b)In situ Hybridization positive (ISH: FISH/CISH/SISH >10% of the invasive tumor cells and by count of at least 20 cells in the area) based on:
?Single probe average HER2 gene copy number f ? 6 signals/cell
?Dual probe HER2/CEP17 ratio ? 2.0 with an average HER2 gene copy number ? 4.0 signals/cell
?Dual probe HER2/CEP17 ratio ? 2.0 with an average HER2 gene copy number < 4.0 signals/cell
?Dual probe HER2/CEP17 ratio < 2.0 with an average HER2 gene copy number ? 6.0 signals/cell
7.Histologically confirmed adenocarcinoma of the breast, MBC or locally advanced breast cancer, eligible for chemotherapy.
a)The patients with locally advanced disease must present recurrent disease or disease progression, which cannot be treated through resection with curative intent. Patients with standard curative options available will not be eligible.
b)In patients with bilateral, HER2+ breast cancer, this must be demonstrated in both sites or in a metastatic biopsy.
8.Measurable or non measurable (but evaluable) disease according to RECIST 1.1 criteria.
9.Adequate organ function, as determined by the following laboratory tests, in the 14 days prior to randomization:
a)Absolute neutrophil count (ANC) ? 1.5 x 109/L.
b)Hemoglobin (Hb: ? 9 g/dL (Transfusion of red blood cells and/or erythropoietin permitted).
c)Platelets > 100,000/mm3
d)Serum creatinine ? 1.5x Upper limit of normal (ULN).
e)Total bilirubin < 1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT and/or ALAT < 2.5 UNL, alkaline phosphatase < 5 UNL (unless bone metastases are present in the absence of any liver disorders).
f)International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) <1.5 x ULN (except in cases of ongoing anticoagulant treatment).
10.Baseline left ventricular ejection fraction (LVEF) ? 50% measured by echocardiography (ECHO) or isotopic ventriculography (MUGA).
11.? HCG pregnancy test negative (serum) for premenopausal women of childbearing potential (biologically capable of having children) and for women who have been menopausal for fewer than 12 months. All patients biologically capable of bearing children must agree and commit to the use of a reliable contraceptive method from 2 weeks prior to the administration of the first dose of the investigational medicinal product until 28 7 months after the last dose of the study treatment.
12.Absence of psychological, family, sociological or geographical conditions that could potentially hinder compliance with the study Protocol and monitoring calendar. These conditions must be discussed w

Exclusion Criteria

1.History of systemic anti cancer therapy for MBC or locally advanced breast cancer, with the exception of previous hormonal treatments.
oThe hormonal regimen for MBC may not include HER2 targeted therapy.
2.Interval <12 months from the last dose of taxanes in the (neo) adjuvant treatment until the time of diagnosis of the metastasis.
3.Hormone therapy up to < 7 days prior to randomization.
4.Trastuzumab, lapatinib and/or pertuzumab in the (neo) adjuvant treatment up to < 21 days prior to randomization.
5.Previous T DM1 treatment.
6.Treatment with any anticancer investigational medicinal product in the 28 days prior the start of the study treatment.
7.History of other malignant tumors in the past 5 years, with the exception of adequately treated in situ carcinoma or stage I of uterine cancer, non melanoma carcinoma of the skin, or other malignant tumors with an expected curative outcome.
8.Brain metastases that have not be treated previously, are progressive, or that require some type of treatment (for example, radiation, surgery or steroids) to control the symptoms in the 60 days prior to the first dose of the study treatment.
9.Radiation therapy for the metastases of the non brain disease carried out in the 14 days prior to inclusion in the study and/or radiation > 30% of the bone marrow.
10.Symptomatic hypercalcemia requiring treatment with bisphosphonates in the 21 days prior to the first study treatment. Patients receiving treatment with bisphosphonates specifically for the prevention of skeletal events and who do not have a RECENTLY history of clinically significant hypercalcemia are eligible.
11.Current peripheral neuropathy, grade ?2 according to NCI CTCAE version 4.03.
12.Abnormal liver function defined as:
o AST or ALT > 2.5 x ULN
o AST or ALT > 1.5 x ULN with simultaneous serum alkaline phosphatase >2.5 x ULN. The serum alkaline phosphatase may be >2.5 x ULN only in the presence of bone metastases and AST (SGOT) and ALT (SGPT) < 1.5 x ULN.
o Total bilirubin ? 1.5 x ULN unless the patient has documented Gilbert's syndrome. In the case of documented Gilbert's syndrome, the direct bilirubin must be within the normal range.
13.History of exposure to the following cumulative doses of anthracyclines:
?Doxorubicin > 500 mg/m2
?Liposomal doxorubicin > 500 mg/m2
?Epirubicin > 720 mg/m2
?Mitoxantrone > 120 mg/m2
?Idarubicin > 90 mg/m2
?If another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 500 mg/m2 of doxorubicin.
14.Cardiopulmonary dysfunction defined as:
o Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) despite optimum medical treatment.
o Serious cardiac arrhythmia or angina controlled inadequately, not controlled with adequate medication.
o Inadequate LVEF at study start, defined as LVEF < 50% in any ECHO or MUGA.
o History of symptomatic congestive heart failure (SCHF): Grade ? 2 according to NCI CTCAE version 4.03 criteria or class ? II according to the criteria of the New York Heart Association (NYHA).
o History of decrease of the LVEF to < 40% or symptomatic CHF after prior treatment with trastuzumab.
o Myocardial infarction in the 6 months prior to randomization.
o Current resting dyspnea due to complications of the advanced malignant disease, or other diseases requiring continuous oxygen therapy.
15. Current uncontrolled serious systemic disease that is active (for example, clinically significant cardiovascular disease, pulm

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified