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

NCT02472964 | Completed Phase 3 Results DMC

• 2 other identifiers: MYL-Her 30012011-001965-42
• Study Type: interventional
• Target: 500
• Locations: 15 countries
• Sites: 92

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  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

Study Arms (2)

Herceptin© + Taxane

ACTIVE COMPARATOR

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; Drug: Paclitaxel; Drug: Docetaxel

MYL- 1401O + Taxane

EXPERIMENTAL

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.

Biological: MYL- 1401O; Drug: Paclitaxel; Drug: Docetaxel

Interventions

Trastuzumab BIOLOGICAL

Trastuzumab 8mg/kg Iv over 90 minutes x 1 then Trastuzumab 6 mg/kg IV over 30 minutes every 3 weeks

Also known as: Herceptin©;

Herceptin© + Taxane

MYL- 1401O BIOLOGICAL

MYL-1401O 8mg/kg Iv over 90 minutes x 1 then HERMyl 1401O Trastuzumab 6 mg/kg IV over 30 minutes every 3 weeks

Also known as: Hercules

MYL- 1401O + Taxane

Paclitaxel DRUG

Paclitaxel 80mg/m2 IV over 60 minutes weekly.

Herceptin© + Taxane; MYL- 1401O + Taxane

Docetaxel DRUG

Docetaxel 75mg/m2 IV over 60 minutes on day 1 of a 3 week cycle

Herceptin© + Taxane; MYL- 1401O + Taxane

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Mylan Inc.: lead
• Mylan GmbH: collaborator

Study Sites (92)

Mylan Investigational Site

Barretos, Brazil

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Mylan Investigational Site

Brasília, Brazil

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Mylan Investigational Site

Goiânia, Brazil

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Mylan Investigational Site

Ijuí, Brazil

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Mylan Investigational Site

Jaú, Brazil

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Mylan Investigational Site

Joinville, Brazil

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Mylan Investigational Site

Morumbi, Brazil

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Porto Alegre, Brazil

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Mylan Investigational Site

Salvador, Brazil

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Mylan Investigational Site

Santo André, Brazil

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São Paulo, Brazil

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Mylan Investigational Site

Sorocaba, Brazil

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Mylan Investigational Site

Santiago, Chile

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Mylan Investigational Site

Temuco, Chile

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Mylan Investigational Site

Batumi, Georgia

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Mylan Investigational Site

Tbilisi, Georgia

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Mylan Investigational Site

Budapest, Hungary

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Debrecen, Hungary

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Mylan Investigational Site

Gyód, Hungary

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Gyula, Hungary

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Miskolc, Hungary

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Nyíregyháza, Hungary

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Szekszárd, Hungary

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Szolnok, Hungary

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Ahmedabad, India

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Bangalore, India

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Chennai, India

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Gūrgaon, India

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Mylan Investigational Site

Hyderabad, India

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Jaipur, India

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Mylan Investigational Site

Karamsad, India

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Mylan Investigational Site

Madurai, India

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Mylan Investigational Site

Mumbai, India

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Nashik, India

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Pune, India

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Surat, India

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Vijaywada, India

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Daugavpils, Latvia

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Leipaja, Latvia

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Riga, Latvia

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Arequipa, Peru

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Lima, Peru

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Mylan Investigational Site

Surquillo, Peru

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Brasov, Romania

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Mylan Investigational Site

Bucharest, Romania

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Mylan Investigational Site

Cluj-Napoca, Romania

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Mylan Investigational Site

Constanța, Romania

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Mylan Investigational Site

Craiva, Romania

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Mylan Investigational Site

Făurei, Romania

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Mylan Investigational Site

Iași, Romania

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Oradea, Romania

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Mylan Investigational Site

Timișoara, Romania

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Arkhangelsk, Russia

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Mylan Investigational Site

Ivanovo, Russia

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Mylan Investigational Site

Kazan', Russia

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Kursk, Russia

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Mylan Investigational Site

Moscow, Russia

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Mylan Investigational Site

Rostov-on-Don, Russia

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Mylan Investigational Site

Ryazan, Russia

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Mylan Investigational Site

Saint Petersburg, Russia

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Mylan Investigational Site

Samara, Russia

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Mylan Investigational Site

Belgrade, Serbia

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Mylan Investigational Site

Kamenica, Serbia

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Mylan Investigational Site

Sremska, Serbia

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Mylan Investigational Site

Bardejov, Slovakia

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Mylan Investigational Site

Košice, Slovakia

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Mylan Investigational Site

Nové Zámky, Slovakia

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Mylan Investigational Site

Trnava, Slovakia

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Mylan Investigator Site

Bloemfontein, South Africa

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Mylan Investigator Site

Durban, South Africa

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Mylan Investigational Site

George, South Africa

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Mylan Investigational Site

Johannesburg, South Africa

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Mylan Investigator Site

Kraaifontein, South Africa

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Mylan Investigational Site

Port Elizabeth, South Africa

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Mylan Investigational Site

Pretoria, South Africa

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Mylan Investigational Site

Vereeniging, South Africa

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Mylan Investigator Site

Bangkok, Thailand

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Mylan Investigator Site

Chiang Mai, Thailand

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Mylan Investigator Site

Phitsanulok, Thailand

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Mylan Investigator Site

Rajthavee, Thailand

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Mylan Investigator Site

Songkhla, Thailand

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Mylan Investigator Site

Ankara, Turkey (Türkiye)

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Mylan Investigator Site

Istanbul, Turkey (Türkiye)

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Mylan Investigator Site

Izmir, Turkey (Türkiye)

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Mylan Investigator Site

Kocaeli, Turkey (Türkiye)

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Mylan Investigator Site

Cherkassy, Ukraine

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Mylan Investigator Site

Chernivtsi, Ukraine

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Mylan Investigator Site

Dnipropetrovsk, Ukraine

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Mylan Investigator Site

Lutsk, Ukraine

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Mylan Investigator Site

Lviv, Ukraine

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Mylan Investigator Site

Sumy, Ukraine

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Mylan Investigator Site

Uzhhorod, Ukraine

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Related Publications (2)

• Rugo HS, Pennella EJ, Gopalakrishnan U, Hernandez-Bronchud M, Herson J, Koch HF, Loganathan S, Deodhar S, Marwah A, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng MLT, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Roy S, Yanez Ruiz EP, Barve A, Fuentes-Alburo A, Waller CF. Final overall survival analysis of the phase 3 HERITAGE study demonstrates equivalence of trastuzumab-dkst to trastuzumab in HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2021 Jul;188(2):369-377. doi: 10.1007/s10549-021-06197-5. Epub 2021 Jun 14.

  PMID: 34125340 DERIVED

• Rugo HS, Barve A, Waller CF, Hernandez-Bronchud M, Herson J, Yuan J, Sharma R, Baczkowski M, Kothekar M, Loganathan S, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng ML, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Ray S, Yanez Ruiz EP, Pennella E; Heritage Study Investigators. Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Randomized Clinical Trial. JAMA. 2017 Jan 3;317(1):37-47. doi: 10.1001/jama.2016.18305.

  PMID: 27918780 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; hercules receptor kinase 2, Arabidopsis; Paclitaxel; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Clinical Program Manager
• Organization: Mylan Inc

gail.tribble@mylan.com

412-651-9530

Study Officials

• Eduardo Pennella, MD

  Mylan Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2015
• First Posted: June 16, 2015
• Study Start: July 1, 2012
• Primary Completion: March 1, 2016
• Study Completion: August 1, 2018
• Last Updated: February 14, 2022
• Results First Posted: October 30, 2018

Record last verified: 2022-02

Locations

LA (3); UA (7); RU (9); SL (4); IN (13); HU (8); GE (2); BR (12); RO (9); TH (5); CL (2); TU (4); PE (3); SE (3); ZA (8)