Study of Efficacy and Safety of Myl1401O + Taxane vs Herceptin©+ Taxane for 1st Line, Met. Br. Ca. (HERiTAge)

February 10, 2022 updated by: Mylan Inc.

A Multicenter, Double-Blind, Randomized, Parallel-Group, Phase III Study of the Efficacy and Safety of Hercules Plus Taxane Versus Herceptin® Plus Taxane as First Line Therapy in Patients With HER2-Positive Metastatic Breast Cancer

A multicenter, double-blind, randomized, parallel-group, Phase III study of the efficacy and safety of Hercules( Myl 1401O, Mylan Trastuzumab) plus taxane versus Herceptin® plus taxane as first line therapy in patients with HER2-positive metastatic breast cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Part 1: A multicenter, double-blind, randomized, parallel-group, Phase III study to compare the efficacy and safety of MYL-1401O (Mylan Trastuzumab biosimiliar) plus taxane versus Herceptin® plus taxane in patients with HER2+ MBC. Either docetaxel or paclitaxel (Investigator site level choice) is planned for at least 24 weeks until documented response to therapy, disease progression, or discontinuation. Disease response and progression will be assessed locally by the Investigator on the basis of clinical and radiographic evidence using RECIST 1.1 criteria. The primary and secondary efficacy analyses will be performed using independently assessed radiographic evidence for the Intent-to-Treat (ITT) population. The primary analysis population for best ORR will be those patients who had measureable disease at baseline and for the secondary endpoint, DR, only those who are responders will be included in the analysis.

Part 2: A multicenter, double-blind, parallel-group study to continue to compare the safety and immunogenicity and efficacy of MYL-1401O versus Herceptin® in patients with HER2+ MBC who have clinical benefit to first-line combination therapy with a taxane. All patients who have at least stable disease (SD), will continue with either single agent MYL-1401O or Herceptin® alone until death, unacceptable toxicity or disease progression.

Population pharmacokinetics: During Part 1 of the study, for both MYL-1401O, and Herceptin® treatment arms, PK sampling for Cmin and Cmax (end of infusion) will be collected for all patients. A PopPK subset, with sufficient samples available to perform the necessary analysis of PopPK modeling will be used to assess AUC, Cmax, Cmin, clearance, Vd, and T1/2 at various time points in the PopPK. Patients randomized into the main study will sign an additional consent form for the PopPK subset. We anticipate that approximately 80 patients will need to be enrolled in this subset collection in order to obtain sufficient samples for analysis.

Long term survival follow-up: OS for this treated population will be determined with every 3 month follow-up until either 240 deaths or 36 months, whichever occurs first, as observed from the time of randomization. The results for OS are expected to be reported March 2019. Exploratory evaluations: In addition, during Part 1 of the study, blood samples will be collected in all patients to assess the impact of soluble shed HER2/ECD on PK and efficacy at pre-dose on Cycles 1, 3, 5, 7, and end of treatment (EOT). Additional samples (ECD) will be obtained on Cycles 9, 13 and every 4 cycles thereafter, EOT and end of study (EOS) for continued evaluation of immunogenicity in patients continuing to receive therapy. A blood sample will be obtained on Cycle 1, Day 1, to be used for assay development and validation

Study Type

Interventional

Enrollment (Actual)

500

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Barretos, Brazil
        • Mylan Investigational Site
      • Brasilia, Brazil
        • Mylan Investigational Site
      • Goiania, Brazil
        • Mylan Investigational Site
      • Ijui, Brazil
        • Mylan Investigational Site
      • Jau, Brazil
        • Mylan Investigational Site
      • Joinville, Brazil
        • Mylan Investigational Site
      • Morumbi, Brazil
        • Mylan Investigational Site
      • Porto Alegre, Brazil
        • Mylan Investigational Site
      • Salvador,, Brazil
        • Mylan Investigational Site
      • Santo Andre, Brazil
        • Mylan Investigational Site
      • Sao Paulo, Brazil
        • Mylan Investigational Site
      • Sorocaba, Brazil
        • Mylan Investigational Site
  • Chile
      • Santiago, Chile
        • Mylan Investigational Site
      • Temuco, Chile
        • Mylan Investigational Site
  • Georgia
      • Batumi, Georgia
        • Mylan Investigational Site
      • Tblisi, Georgia
        • Mylan Investigational Site
  • Hungary
      • Budapest, Hungary
        • Mylan Investigational Site
      • Debrecen, Hungary
        • Mylan Investigational Site
      • Gyod, Hungary
        • Mylan Investigational Site
      • Gyula, Hungary
        • Mylan Investigational Site
      • Miskolc, Hungary
        • Mylan Investigational Site
      • Nyiregyhaza, Hungary
        • Mylan Investigational Site
      • Szekszard, Hungary
        • Mylan Investigational Site
      • Szolnok, Hungary
        • Mylan Investigational Site
  • India
      • Ahmedabad, India
        • Mylan Investigational Site
      • Bangalore, India
        • Mylan Investigational Site
      • Chennai, India
        • Mylan Investigational Site
      • Gurgaon, India
        • Mylan Investigational Site
      • Hyderabad, India
        • Mylan Investigational Site
      • Jaipur, India
        • Mylan Investigational Site
      • Karamsad, India
        • Mylan Investigational Site
      • Madurai, India
        • Mylan Investigational Site
      • Mumbai, India
        • Mylan Investigational Site
      • Nashik, India
        • Mylan Investigational Site
      • Pune, India
        • Mylan Investigational Site
      • Surat, India
        • Mylan Investigational Site
      • Vijaywada, India
        • Mylan Investigational Site
  • Latvia
      • Daugavpils, Latvia
        • Mylan Investigational Site
      • Leipaja, Latvia
        • Mylan Investigational Site
      • Riga, Latvia
        • Mylan Investigational Site
  • Peru
      • Arequipa, Peru
        • Mylan Investigational Site
      • Lima, Peru
        • Mylan Investigational Site
      • Surquillo, Peru
        • Mylan Investigational Site
  • Romania
      • Brasov, Romania
        • Mylan Investigational Site
      • Bucharest, Romania
        • Mylan Investigational Site
      • Bucuresti, Romania
        • Mylan Investigational Site
      • Cluj- Napoca, Romania
        • Mylan Investigational Site
      • Constanta, Romania
        • Mylan Investigational Site
      • Craiva, Romania
        • Mylan Investigational Site
      • Filimon Sirbu, Romania
        • Mylan Investigational Site
      • Iasi, Romania
        • Mylan Investigational Site
      • Oradea, Romania
        • Mylan Investigational Site
      • Timisoara, Romania
        • Mylan Investigational Site
  • Russian Federation
      • Arkhangelsk, Russian Federation
        • Mylan Investigational Site
      • Ivanovo, Russian Federation
        • Mylan Investigational Site
      • Kazan, Russian Federation
        • Mylan Investigational Site
      • Kursk, Russian Federation
        • Mylan Investigational Site
      • Moscow, Russian Federation
        • Mylan Investigational Site
      • Rostov-On-Don, Russian Federation
        • Mylan Investigational Site
      • Ryazan, Russian Federation
        • Mylan Investigational Site
      • Samara, Russian Federation
        • Mylan Investigational Site
      • St. Petersburg, Russian Federation
        • Mylan Investigational Site
  • Serbia
      • Belgrade, Serbia
        • Mylan Investigational Site
      • Kamenica, Serbia
        • Mylan Investigational Site
      • Sremska, Serbia
        • Mylan Investigational Site
  • Slovakia
      • Bardejov, Slovakia
        • Mylan Investigational Site
      • Kosice, Slovakia
        • Mylan Investigational Site
      • Nove Zamky, Slovakia
        • Mylan Investigational Site
      • Trnava, Slovakia
        • Mylan Investigational Site
  • South Africa
      • Bloemfontein, South Africa
        • Mylan Investigator Site
      • Durban, South Africa
        • Mylan Investigator Site
      • George, South Africa
        • Mylan Investigational Site
      • Johannesburg, South Africa
        • Mylan Investigational Site
      • Kraaifontein, South Africa
        • Mylan Investigator Site
      • Port Elizabeth, South Africa
        • Mylan Investigational Site
      • Pretoria, South Africa
        • Mylan Investigational Site
      • Vereeniging, South Africa
        • Mylan Investigational Site
  • Thailand
      • Bangkok, Thailand
        • Mylan Investigator Site
      • Chiang mai, Thailand
        • Mylan Investigator Site
      • Phitsanulok, Thailand
        • Mylan Investigator Site
      • Rajthavee, Thailand
        • Mylan Investigator Site
      • Songkla, Thailand
        • Mylan Investigator Site
  • Turkey
      • Ankara, Turkey
        • Mylan Investigator Site
      • Istanbul, Turkey
        • Mylan Investigator Site
      • Izmir, Turkey
        • Mylan Investigator Site
      • Kocaeli, Turkey
        • Mylan Investigator Site
  • Ukraine
      • Cherkassy, Ukraine
        • Mylan Investigator Site
      • Chernivtsi, Ukraine
        • Mylan Investigator Site
      • Dnipropetrovsk, Ukraine
        • Mylan Investigator Site
      • Lutsk, Ukraine
        • Mylan Investigator Site
      • Lviv, Ukraine
        • Mylan Investigator Site
      • Sumy, Ukraine
        • Mylan Investigator Site
      • Uzhgorod, Ukraine
        • Mylan Investigator Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Locally recurrent or MBC that is not amenable to curative surgery and/or radiation.

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 the sponsor-identified central laboratory prior to randomization. Archival tumor tissue samples can be used.

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.

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.

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.

Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 2

  • Serum creatinine ≤1.5 x ULN (upper limit of normal),
  • Total bilirubin ≤1.0 x ULN (>1.0 x 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.

Left ventricular ejection fraction (LVEF) within institutional range of normal as measured by multiple gated acquisition scan or echocardiogram.

Exclusion Criteria:

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.

Prior treatment with neoadjuvant or adjuvant anthracyclines with a cumulative dose of doxorubicin of >400 mg/m2, epirubicin dose >800 mg/m2.

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.

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.

Presence of unstable angina or a history of congestive heart failure 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.

Peripheral sensory or motor neuropathy Grade 2 or higher according to the National Cancer Institute-Common Terminology Criteria (NCI-CTC) Version 4.03 [19].

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.

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).

Complete listing of Inc/Excl. within protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Herceptin© + Taxane

Part 1: Herceptin© (trastuzumab) intravenously+ paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.

Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to Herceptin© (trastuzumab) alone once every 3 weeks until DP or subject withdrawal .
Biological: Trastuzumab
Trastuzumab 8mg/kg Iv over 90 minutes x 1 then Trastuzumab 6 mg/kg IV over 30 minutes every 3 weeks
Other Names:
  • Herceptin©;
Drug: Paclitaxel
Paclitaxel 80mg/m2 IV over 60 minutes weekly.
Drug: Docetaxel
Docetaxel 75mg/m2 IV over 60 minutes on day 1 of a 3 week cycle
Experimental: MYL- 1401O + Taxane

Part 1:MYL-1401O Intravenously + paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.

Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to MYL-1401O alone once every 3 weeks until DP or subject withdrawal.
Drug: Paclitaxel
Paclitaxel 80mg/m2 IV over 60 minutes weekly.
Drug: Docetaxel
Docetaxel 75mg/m2 IV over 60 minutes on day 1 of a 3 week cycle
Biological: MYL- 1401O
MYL-1401O 8mg/kg Iv over 90 minutes x 1 then HERMyl 1401O Trastuzumab 6 mg/kg IV over 30 minutes every 3 weeks
Other Names:
  • Hercules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Endpoint : Compare Best Overall Response Rate (ORR) (According to Response Evaluation Criteria in Solid Tumor [RECIST] 1.1 Criteria) at Week 24 of MYL-1401O Plus Taxane Versus Herceptin® Plus Taxane in the ITT1 Population
Time Frame: from time of First treatment to week 24

Tumor measurements were perform by centralized blinded reviewers using RECIST 1.1 criteria. Per RECIST 1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to <10 mm.Partial Response (PR): >/= 30% decrease sum of the diameters of target lesions from baseline sum diameters.

Progressive Disease (PD): </= 20% increase in the sum of the diameters of target lesions, from the smallest sum on study with at least a 5 mm absolute increase in the sum of all lesions. The appearance of one or more new lesions* denotes disease progression.

Stable Disease (SD): Neither sufficient decrease or increase. Evaluation of Non-Target Lesions Complete Response (CR): Disappearance of all non-target lesions. Non-complete Response/Non-Progressive Disease: Persistence of one or more non-target lesions. Progressive Disease (PD): Substantial, unequivocal progression of existing non-target lesions.
from time of First treatment to week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mylan Inc.

Collaborators

Mylan GmbH

Investigators

  • Study Director: Eduardo Pennella, MD, Mylan Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2012

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

August 1, 2018

Study Registration Dates

First Submitted

June 3, 2015

First Submitted That Met QC Criteria

June 11, 2015

First Posted (Estimate)

June 16, 2015

Study Record Updates

Last Update Posted (Actual)

February 14, 2022

Last Update Submitted That Met QC Criteria

February 10, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MYL-Her 3001
  • 2011-001965-42 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on Trastuzumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Norway

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe