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

Breast Cancer Clinical Trial

— HERiTAge  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02472964
• Other study ID #: MYL-Her 3001
• Secondary ID: 2011-001965-42
• Status: Completed
• Phase: Phase 3
• Start date: July 2012
• Est. completion date: August 2018

Study information

• Verified date: February 2022
• Source: Viatris Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: August 2018
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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

Drug:
• Paclitaxel
Paclitaxel 80mg/m2 IV over 60 minutes weekly.
• Docetaxel
Docetaxel 75mg/m2 IV over 60 minutes on day 1 of a 3 week cycle

Locations

Country	Name	City	State
Brazil	Mylan Investigational Site	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
Chile	Mylan Investigational Site	Santiago
Chile	Mylan Investigational Site	Temuco
Georgia	Mylan Investigational Site	Batumi
Georgia	Mylan Investigational Site	Tblisi
Hungary	Mylan Investigational Site	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
India	Mylan Investigational Site	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
Latvia	Mylan Investigational Site	Daugavpils
Latvia	Mylan Investigational Site	Leipaja
Latvia	Mylan Investigational Site	Riga
Peru	Mylan Investigational Site	Arequipa
Peru	Mylan Investigational Site	Lima
Peru	Mylan Investigational Site	Surquillo
Romania	Mylan Investigational Site	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
Russian Federation	Mylan Investigational Site	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
Serbia	Mylan Investigational Site	Belgrade
Serbia	Mylan Investigational Site	Kamenica
Serbia	Mylan Investigational Site	Sremska
Slovakia	Mylan Investigational Site	Bardejov
Slovakia	Mylan Investigational Site	Kosice
Slovakia	Mylan Investigational Site	Nove Zamky
Slovakia	Mylan Investigational Site	Trnava
South Africa	Mylan Investigator Site	Bloemfontein
South Africa	Mylan Investigator Site	Durban
South Africa	Mylan Investigational Site	George
South Africa	Mylan Investigational Site	Johannesburg
South Africa	Mylan Investigator Site	Kraaifontein
South Africa	Mylan Investigational Site	Port Elizabeth
South Africa	Mylan Investigational Site	Pretoria
South Africa	Mylan Investigational Site	Vereeniging
Thailand	Mylan Investigator Site	Bangkok
Thailand	Mylan Investigator Site	Chiang mai
Thailand	Mylan Investigator Site	Phitsanulok
Thailand	Mylan Investigator Site	Rajthavee
Thailand	Mylan Investigator Site	Songkla
Turkey	Mylan Investigator Site	Ankara
Turkey	Mylan Investigator Site	Istanbul
Turkey	Mylan Investigator Site	Izmir
Turkey	Mylan Investigator Site	Kocaeli
Ukraine	Mylan Investigator Site	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

Sponsors (2)

Lead Sponsor	Collaborator
Mylan Inc.	Mylan GmbH

Countries where clinical trial is conducted

Brazil,  Chile,  Georgia,  Hungary,  India,  Latvia,  Peru,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Thailand,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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): 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