Study of safety and efficacy of Hercules versus Herceptin® in patients with breast cancer

Phase 1

• Conditions: Human Epidermal Growth Factor Receptor 2 positive (HER2+) metastatic breast cancer (MBC); MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000020826; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-001965-42-CZ
• Lead Sponsor: MYLAN GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-01-22
• Last Update Posted: 6 November 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 456

Inclusion Criteria

1.=18 years of age.
2.Histologically confirmed diagnosis of breast cancer.
3.Locally recurrent or MBC that is not amenable to curative surgery and/or radiation.
4.Documentation of HER2 gene amplification by fluorescent in situ hybridization (FISH); as defined by a ratio >2.0) or documentation of HER2-overexpression by immunohistochemistry (IHC) (defined as IHC3+, or IHC2+ with FISH confirmation) based on sponsor-identified central laboratory prior to randomization (see Section 7.1.1). Archival tumor tissue samples can be used.
5.Documentation of estrogen receptor/progesterone receptor (ER/PgR) status (positive or negative) based on either a local or central laboratory report must be available before randomization.
6.Pathologically confirmed breast cancer with at least one measurable metastatic target lesion (based on RECIST criteria, Version 1.1). Bone, central nervous system (CNS), and skin lesions, as well as lesions that were irradiated, biopsied or had any form of local intervention or surgical manipulation are only to be assessed as non-target lesions. Baseline imaging studies and submitted for central confirmation of target lesions must have been performed in the 4 weeks preceding randomization.
7.Patients with a history of CNS metastases or cord compression are eligible if they have been successfully treated and are off steroids for at least 4 weeks before first dose of investigational product. Patients with newly detected CNS metastases must be successfully treated (e.g., radiotherapy, stereotactic radiosurgery) before being considered for the trial. Patients with known or suspected brain metastases must undergo a baseline brain computed tomography (CT) or magnetic resonance imaging (MRI).
8.Patients previously treated with trastuzumab or lapatinib in the adjuvant setting are allowed if metastatic disease was diagnosed at least one year after the last dose of treatment.
9.Prior treatment with hormonal agents or bisphosphonates/denosumab is allowed. Bisphosphonates/denosumab can be given simultaneously with study treatment but cannot start after randomization and is considered an indication of progressive disease (PD). Hormonal agents must be discontinued prior to beginning study therapy.
10.Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 2.
11.Screening laboratory values within the following parameters:
•Absolute neutrophil count (ANC) =1.5 x 109/L (1500/mm3).
•Platelet count =100 x 109/L (100,000/mm3).
•Hemoglobin =9.0 g/dL (90 g/L), without a prior transfusion in the last 2 weeks.
•Serum creatinine =1.5 x upper limit of normal (ULN).
•Total bilirubin =1.0 x ULN (>1 ULN if documented Gilbert’s disease).
•Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =2.5 x ULN.
•AST and/or ALT <1.5 x ULN, if alkaline phosphatase > 2.5 x ULN.
•Alkaline phosphatase >2.5 x ULN, if bone metastases present and no liver dysfunction present.
12.Left ventricular ejection fraction (LVEF) within institutional range of normal as measured by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO).
13.The patient is willing to comply with the protocol and procedures for the duration of the study, including all scheduled visits and examinations.
14.The patient is either not of childbearing potential or is willing to practice birth control by using two different highly effective methods of contraception, or abstain from sexual intercourse for the duration of the study and follo

Exclusion Criteria

1.Prior systemic therapy in the metastatic disease setting. This includes: chemotherapy, signal transduction inhibitors (e.g., lapatinib), HER2 targeted therapy (e.g., trastuzumab), or other investigational anticancer therapy.
2.Prior treatment with neoadjuvant or adjuvant anthracyclines with a cumulative dose of doxorubicin of >400 mg/m2, epirubicin dose >800 mg/m2.
3.Participation in the active treatment phase of an investigational drug study =28 days prior to randomization.
4.Patients with bone or skin as the only site of disease. Patients with skin lesions measurable by CT scans or MRI as only site of measurable disease are allowed.
5.Surgery or radiotherapy =2 weeks preceding Day 1. Target lesions have to be outside the irradiated fields and the patient has fully recovered from surgery or radiotherapy.
6.Presence of unstable angina or a history of CHF according to the New York Heart Association criteria, history of myocardial infarction <1 year from randomization, clinically significant valvular disease, serious cardiac arrhythmia requiring treatment, uncontrolled hypertension or known pulmonary hypertension.
7.Peripheral sensory or motor neuropathy Grade 2 or higher according to the National Cancer Institute-Common Terminology Criteria (NCI-CTC) Version 4.03 [19].
8.Any other cancer, including contralateral breast cancer, within 5 years prior to screening with the exception of adequately treated ductal carcinoma in situ, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.
9.Immunocompromized patients, including known seropositivity for human immunodeficiency virus, or current or chronic hepatitis B and/or hepatitis C infection (as detected by positive testing for hepatitis B surface antigen or antibody to hepatitis C virus with confirmatory testing).
10.Patients with documented severe hypersensitivity reaction to trastuzumab, paclitaxel, docetaxel or excipients used in their formulations, including murine protein remnants and patients with hereditary fructose intolerance.
11.Evidence of significant medical illness or abnormal laboratory finding (including dyspnea at rest or serious pulmonary illness) that, in the Investigator’s judgment, will substantially increase the risk associated with the patient’s participation in, and completion of, the study, or could preclude the evaluation of the patient’s response.

Study & Design

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