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Breast CancerPhase 3HERiTAgeNCT02472964

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

A Phase 3 study testing Trastuzumab, MYL- 1401O and Paclitaxel in people with Breast Cancer, run by Mylan Inc. at 92 sites in 15 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Trastuzumab, MYL- 1401O and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
500 participants
Where
92 sitesin 15 countries
Study dates
Jul 2012to Aug 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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.

Who cannot join

  • 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].
Show all 9Show fewer
  • 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

Trial locations and contacts

92 sites in 15 countries.

92 sites in 15 countries

India13 sites

  • Mylan Investigational Site

    Ahmedabad

  • Mylan Investigational Site

    Bangalore

  • Mylan Investigational Site

    Chennai

  • Mylan Investigational Site

    Gūrgaon

  • Mylan Investigational Site

    Hyderabad

  • Mylan Investigational Site

    Jaipur

  • Mylan Investigational Site

    Karamsad

  • Mylan Investigational Site

    Madurai

  • Mylan Investigational Site

    Mumbai

  • Mylan Investigational Site

    Nashik

  • Mylan Investigational Site

    Pune

  • Mylan Investigational Site

    Surat

  • Mylan Investigational Site

    Vijaywada

Other trials in India

Brazil12 sites

  • Mylan Investigational Site

    Barretos

  • Mylan Investigational Site

    Brasília

  • Mylan Investigational Site

    Goiânia

  • Mylan Investigational Site

    Ijuí

  • Mylan Investigational Site

    Jaú

  • Mylan Investigational Site

    Joinville

  • Mylan Investigational Site

    Morumbi

  • Mylan Investigational Site

    Porto Alegre

  • Mylan Investigational Site

    Salvador

  • Mylan Investigational Site

    Santo André

  • Mylan Investigational Site

    São Paulo

  • Mylan Investigational Site

    Sorocaba

Other trials in Brazil

Romania9 sites

  • Mylan Investigational Site

    Brasov

  • Mylan Investigational Site

    Bucharest

  • Mylan Investigational Site

    Cluj-Napoca

  • Mylan Investigational Site

    Constanța

  • Mylan Investigational Site

    Craiva

  • Mylan Investigational Site

    Făurei

  • Mylan Investigational Site

    Iași

  • Mylan Investigational Site

    Oradea

  • Mylan Investigational Site

    Timișoara

Other trials in Romania

Russia9 sites

  • Mylan Investigational Site

    Arkhangelsk

  • Mylan Investigational Site

    Ivanovo

  • Mylan Investigational Site

    Kazan'

  • Mylan Investigational Site

    Kursk

  • Mylan Investigational Site

    Moscow

  • Mylan Investigational Site

    Rostov-on-Don

  • Mylan Investigational Site

    Ryazan

  • Mylan Investigational Site

    Saint Petersburg

  • Mylan Investigational Site

    Samara

Other trials in Russia

Hungary8 sites

  • Mylan Investigational Site

    Budapest

  • Mylan Investigational Site

    Debrecen

  • Mylan Investigational Site

    Gyód

  • Mylan Investigational Site

    Gyula

  • Mylan Investigational Site

    Miskolc

  • Mylan Investigational Site

    Nyíregyháza

  • Mylan Investigational Site

    Szekszárd

  • Mylan Investigational Site

    Szolnok

Other trials in Hungary

South Africa8 sites

  • Mylan Investigator Site

    Bloemfontein

  • Mylan Investigator Site

    Durban

  • Mylan Investigational Site

    George

  • Mylan Investigational Site

    Johannesburg

  • Mylan Investigator Site

    Kraaifontein

  • Mylan Investigational Site

    Port Elizabeth

  • Mylan Investigational Site

    Pretoria

  • Mylan Investigational Site

    Vereeniging

Other trials in South Africa

Ukraine7 sites

  • Mylan Investigator Site

    Cherkassy

  • Mylan Investigator Site

    Chernivtsi

  • Mylan Investigator Site

    Dnipropetrovsk

  • Mylan Investigator Site

    Lutsk

  • Mylan Investigator Site

    Lviv

  • Mylan Investigator Site

    Sumy

  • Mylan Investigator Site

    Uzhhorod

Other trials in Ukraine

Thailand5 sites

  • Mylan Investigator Site

    Bangkok

  • Mylan Investigator Site

    Chiang Mai

  • Mylan Investigator Site

    Phitsanulok

  • Mylan Investigator Site

    Rajthavee

  • Mylan Investigator Site

    Songkhla

Other trials in Thailand

Slovakia4 sites

  • Mylan Investigational Site

    Bardejov

  • Mylan Investigational Site

    Košice

  • Mylan Investigational Site

    Nové Zámky

  • Mylan Investigational Site

    Trnava

Other trials in Slovakia

Turkey (Türkiye)4 sites

  • Mylan Investigator Site

    Ankara

  • Mylan Investigator Site

    Istanbul

  • Mylan Investigator Site

    Izmir

  • Mylan Investigator Site

    Kocaeli

Other trials in Turkey (Türkiye)

Latvia3 sites

  • Mylan Investigational Site

    Daugavpils

  • Mylan Investigational Site

    Leipaja

  • Mylan Investigational Site

    Riga

Other trials in Latvia

Peru3 sites

  • Mylan Investigational Site

    Arequipa

  • Mylan Investigational Site

    Lima

  • Mylan Investigational Site

    Surquillo

Other trials in Peru

Serbia3 sites

  • Mylan Investigational Site

    Belgrade

  • Mylan Investigational Site

    Kamenica

  • Mylan Investigational Site

    Sremska

Other trials in Serbia

Chile2 sites

  • Mylan Investigational Site

    Santiago

  • Mylan Investigational Site

    Temuco

Other trials in Chile

Georgia2 sites

  • Mylan Investigational Site

    Batumi

  • Mylan Investigational Site

    Tbilisi

Other trials in Georgia

About this study

Official title: 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.

Read the 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

Conditions
Breast Cancer
Being tested
Trastuzumab, MYL- 1401O, Paclitaxel, Docetaxel
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrastuzumabBiological

    Also called Herceptin©;

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

  • MYL- 1401OBiological

    Also called Hercules

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

  • PaclitaxelDrug

    Paclitaxel 80mg/m2 IV over 60 minutes weekly.

  • DocetaxelDrug

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

Study groups in NCT02472964
Study groupRoleWhat they receive
Herceptin© + TaxaneActive comparatorPart 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 .
Receives: Biological: Trastuzumab; Drug: Paclitaxel; Drug: Docetaxel
MYL- 1401O + TaxaneExperimentalPart 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.
Receives: Biological: MYL- 1401O; Drug: Paclitaxel; Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: from time of First treatment to week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2015 (estimated)
  2. Study startJul 2012
  3. Primary completionMar 2016
  4. Study completionAug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
500 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02472964
Sponsor's protocol ID
MYL-Her 3001
Other IDs
2011-001965-42
Acronym
HERiTAge
Status last verified
Feb 2022
First submitted
3 Jun 2015
Last updated
14 Feb 2022
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 34125340

  • 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.

    PubMed 27918780

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Trastuzumab, MYL- 1401O and Paclitaxel in people with Breast Cancer, run by Mylan Inc. at 92 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 92 sites in India, Brazil, Romania, Russia, Hungary and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02472964, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2022.

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