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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02472964
Recruitment Status : Completed
First Posted : June 16, 2015
Results First Posted : October 30, 2018
Last Update Posted : February 14, 2022
Sponsor:
Collaborator:
Mylan GmbH
Information provided by (Responsible Party):
Viatris Inc. ( Mylan Inc. )

Tracking Information
First Submitted Date  ICMJE June 3, 2015
First Posted Date  ICMJE June 16, 2015
Results First Submitted Date  ICMJE October 12, 2017
Results First Posted Date  ICMJE October 30, 2018
Last Update Posted Date February 14, 2022
Study Start Date  ICMJE July 2012
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 29, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 11, 2015)
compare best overall response rate (ORR) (according to Response Evaluation Criteria in Solid Tumor [RECIST] 1.1 criteria) at Week 24 with Hercules( Myl 1401O, Mylan Trastuzumab) in combination with taxane versus Herceptin® plus taxane [ Time Frame: from time of First treatment to week 24 ]
RECIST 1.1 evaluation for overall response rate at 6 week intervals
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2015)
  • time to tumor progression (TTP); [ Time Frame: from time of first treatment to week 24 at every 6 week intervals ]
  • •overall survival (OS) [ Time Frame: from time of first treatment to week 24 at every 6 week intervals ]
  • duration of response (DR). [ Time Frame: from time of first treatment to week 24 at every 6 week intervals ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy and Safety of Myl1401O + Taxane vs Herceptin©+ Taxane for 1st Line, Met. Br. Ca.
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Biological: Trastuzumab
    Trastuzumab 8mg/kg Iv over 90 minutes x 1 then Trastuzumab 6 mg/kg IV over 30 minutes every 3 weeks
    Other Name: Herceptin©;
  • 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 Name: Hercules
  • 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
Study Arms  ICMJE
  • 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 .

    Interventions:
    • Biological: Trastuzumab
    • Drug: Paclitaxel
    • Drug: Docetaxel
  • 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.

    Interventions:
    • Biological: MYL- 1401O
    • Drug: Paclitaxel
    • Drug: Docetaxel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 29, 2018)
500
Original Estimated Enrollment  ICMJE
 (submitted: June 11, 2015)
600
Actual Study Completion Date  ICMJE August 2018
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Chile,   Georgia,   Hungary,   India,   Latvia,   Peru,   Romania,   Russian Federation,   Serbia,   Slovakia,   South Africa,   Thailand,   Turkey,   Ukraine
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02472964
Other Study ID Numbers  ICMJE MYL-Her 3001
2011-001965-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Viatris Inc. ( Mylan Inc. )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Mylan Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Mylan GmbH
Investigators  ICMJE
Study Director: Eduardo Pennella, MD Mylan Inc.
PRS Account Viatris Inc.
Verification Date February 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP