Phase III multicenter, double-blind, randomized, parallel-group study to evaluate safety and efficacy of Hercules plus Taxane Herceptin® plus Taxane as First Line therapy in Her2-Positive Metastatic Breast cancer.

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2014/12/005334
• Date of registration: 30-12-2014
• Prospective Registration: No
• Primary sponsor: Mylan GmbH
• Public title: Phase III multicenter, double-blind, randomized, parallel-group study to evaluate safety and efficacy of Hercules plus Taxane Herceptin® plus Taxane as First Line therapy in Her2-Positive Metastatic Breast cancer.
• Scientific title: MYL-Her3001: 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
• Date of first enrolment: 12-12-2014
• Target sample size: 600
• Recruitment status: Open to Recruitment
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=10578
• Study type: Interventional
• Study design: Randomized, Parallel Group, Multiple Arm Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
• Phase: Phase 3

Countries of recruitment

Argentina, Austria, Brazil, Bulgaria, Canada, Chile, Czech Republic, Egypt, France, Georgia, Germany, Greece, Hungary, India, Latvia, Lebanon, Mexico, Peru, Philippines, Poland, Romania, Russian Federation, Serbia , Slovakia, South Africa, Spain, Taiwan, Thailand, Turkey, Ukraine, United States of America

Contacts

• Name: Mamta Singh
• Affiliation: INC Research CDS Services Pvt. Ltd.,

• Name: Bhawana Awasthy
• Affiliation: INC Research CDS Services Pvt. Ltd.,

Key inclusion & exclusion criteria

Inclusion criteria: Subjects must meet the following criteria to be included in the study:

1.Female/male grater and equal to 18 years of age

2. Histologically confirmed diagnosis of breast cancer

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

4. 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. 5. Documentation of estrogen receptor/progesterone receptor (ER/PgR) status (positive or negative) based on either a local or central laboratory report must be available before randomization

6. Pathologically confirmed breast cancer with at least one measurable metastatic target lesion (based on RECIST criteria, version 1.1. Bone central nervous system 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. Baseline imaging studies of target lesions must have been performed and submitted for central confirmation in the 4 weeks preceding randomization.

7. Patients with a history of CNS metastases or cord compression are eligible if they have been successfully treated and are off steroids for at least 4 weeks before first dose of investigational product. Patients with newly detected CNS metastases must be successfully treated eg radiotherapy, stereotactic radiosurgery) before being considered for the trial. Patients with known or suspected brain metastases must undergo a baseline brain computed tomography or magnetic resonance imaging.



8. 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.

9. 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 . Hormonal agents must be discontinued prior to beginning study therapy





10. Eastern Cooperative Oncology Group performance status of 0 - 2.

11. Screening laboratory values within the following parameters:

ANC greater than equal to1.5 x 109/L (1500/mm3), Platelet count greater than equal to100 x 109/L (100,000/mm3), Hemoglobin greater than equal to 9.0 g/dL (90 g/L) without a prior transfusion in the last 2 weeks, Serum creatinine less than equal to 1.5 x ULN (upper limit of normal), Total bilirubin less than equal to 1.0 x ULN (grater than 1.0 x ULN if documented Gilbertâ??s disease), AST and/or ALT less than equal to 2.5 x ULN, AST and/or ALT less than 1.5 x ULN if alkaline phosphatase greater than 2.5 x ULN, Alkaline phosphatase greater than 2.5 x ULN;if bone metastases
Exclusion criteria: 1. 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.

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

3. Participation in the active treatment phase of an investigational drug study less than equal to 8 days prior to randomization

4. 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.

5. Surgery or radiotherapy less than equal to 2 weeks preceding Day 1. Target lesions have to be outside the irradiated fields and the patient has fully recovered from surgery or radiotherapy

6. Presence of unstable angina or a history of congestive heart failure according to the New York Heart Association criteria, history of myocardial infarction less than 1 year from randomization, clinically significant valvular disease, serious cardiac arrhythmia requiring treatment, uncontrolled hypertension or known pulmonary hypertension

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



8.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

9. 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)

10. Patients with documented severe hypersensitivity reaction to trastuzumab, paclitaxel, docetaxel or excipients used in their formulations, including murine protein remnants

11. Evidence of significant medical illness (including dyspnea at rest or serious pulmonary illness, etc.) or abnormal laboratory finding that, in the Investigatorâ??s judgment, will substantially increase the risk associated with the patientâ??s participation in, and completion of, the study, or could preclude the evaluation of the patientâ??s response





Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Drug will be tested in HER and MBC patients

Intervention(s)

Intervention1: Hercules (trastuzumab): 8mg per kg loading dose at the start of treatment. therefater 6 mg per kg contineous dose by I.V
Control Intervention1: Herceptin: 8 mg per kg loading dose at the start of treatment by continuous i.v. infusion over 90 minutes.

Primary Outcome(s)

The primary efficacy endpoint is the is the best ORR where objective response is defined as a CR or PR according to RECIST 1.1 based on centralized review evaluation acheived at 24 weeks after start of treatment. Only patients with measurable disease at baseline will be included in the analysis of objective response.Timepoint: To continue to evaluate the safety and tlerability profile of hercules and herceptin given as a single agent.

To compare the immunogencity of hercules and herceptin by examining the clinical immunogenic response

Secondary Outcome(s)

To compare clinical activity at week 48 between treatment arms by measuring; PFS, OS and DR, and OS at 36 months of after 300 deaths, whichever occurs first, as observed from the time od randomization.Timepoint: Compare independently assessed clinical activity at week 24 between treatment arms. To descriptively compare the safety, immunogenicity and tolerability profile.

To compare the immunogenicity of herculues and Herceptin.

To compare the population PoP PK area

Secondary ID(s)

MYL-Her 3001 Amend 2; version 5.0 dated 11 Oct 2013

Source(s) of Monetary Support

Mylan GmbH

Secondary Sponsor(s)

INC Research CDS Services Private Limited

Ethics review

Status: Approved
Approval date: 22/05/2014
Contact:

Ethics Committee, Jehangir Clinical Development Centre Pvt. Jehangir Hospital Premises

Status: Approved
Approval date: 21/06/2014
Contact:

HCG Multi Specialty Ethics Committee

Status: Approved
Approval date: 05/07/2014
Contact:

Narayana Health Medical Ethics Committee

Status: Approved
Approval date: 07/07/2014
Contact:

Institutional Ethics committee- Meenakshi Mission Hospital

Status: Approved
Approval date: 23/07/2014
Contact:

Ethics Committee - Apex Hospital

Status: Approved
Approval date: 24/07/2014
Contact:

Ethics Committee- MS Ramaiah

Status: Approved
Approval date: 26/07/2014
Contact:

Poona Medical Research Foundation Institutional Ethics Committee

Status: Approved
Approval date: 04/08/2014
Contact:

Shatabdi Hospital Ethics Committee

Status: Approved
Approval date: 09/09/2014
Contact:

Manavata Clinical Research Institute Ethics Committee (MCRI EC),

Status: Approved
Approval date: 20/10/2014
Contact:

Apple Hospital Ethics Committee

Status: Approved
Approval date: 01/12/2014
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Human Research Ethics Committee

Status: Approved
Approval date: 14/02/2015
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Institutional Ethics Committee - FMRI

Status: Approved
Approval date: 27/02/2015
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SCCH - Institutional Ethics Committee

Status: Approved
Approval date: 03/03/2015
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Institutional Ethics Committee City Cancer Centre

Status: Approved
Approval date: 28/03/2015
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HCG-Central Ethics committee

Status: Approved
Approval date: 17/04/2015
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Institutional Ethics Committee- BIACH and RI

Status: Approved
Approval date: 22/04/2015
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Institutional Ethics Committee - TMH

Status: Approved
Approval date: 22/04/2015
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Institutional Ethics Committee-Clinical Studies

Status: Approved
Approval date: 02/05/2015
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Institutional Ethics Committee - PVS Hospital

Status: Approved
Approval date: 08/05/2015
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Institutional Ethics Committee- BGS Global Hospitals

Status: Not Approved
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Bhakti Vedanta Hospital Ethics Committee

Status: Not Approved
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Institutional Ethics Committee - BMCHRC

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Institutional Ethics Committee - GKNMH

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Institutional Ethics Committee - Sri Ramachandra University

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Institutional Ethics Committee - VGM Hospital

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Institutional Ethics Committee- Omega Hospitals

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Research Cell - KGMC