- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06038539
Efficacy and Safety of the Proposed Biosimilar Pertuzumab (PERT-IJS) Versus EU-Perjeta® Along With Trastuzumab and Chemotherapy (Carboplatin and Docetaxel) as Neoadjuvant Treatment in Chemotherapy naïve Patients With Early Stage or Locally Advanced HR Negative and HER2 Positive Breast Cancer
A Multicenter, Double-blind, Randomized, Parallel-group, Phase 3 Study to Compare the Efficacy and Safety of the Proposed Biosimilar PERT-IJS and EU-Perjeta® Along With Trastuzumab and Chemotherapy (Carboplatin and Docetaxel) as Neoadjuvant Treatment in Patients With Hormone Receptor Negative (HR-ve) Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Stage or Locally Advanced Breast Cancer
Study Overview
Status
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Anoop Chullikana, MBBS, MD
- Phone Number: 5306 91 80 2808
- Email: anoop.chullikana@biocon.com
Study Contact Backup
- Name: Jayanti Panda, MBA,PM
- Phone Number: 5304 91 80 2808
- Email: jayanti.panda@biocon.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patient willing and able to sign informed consent and to follow the protocol requirements
- Female patients aged ≥ 18 years at the time of Screening
- Patient with Eastern Cooperative Oncology Group (ECOG) Performance Status < 2
Patients with breast cancer that meets the following criteria:
- A known case of histologically confirmed invasive breast carcinoma with a primary tumor size of > 2 cm by standard local assessment technique
- stage at presentation: early stage (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0; T4a-c, any N, M0) or inflammatory (T4d, any N, M0)
- Patients with HER2 overexpression by Immunohistochemistry (IHC) (defined as IHC 3+, or IHC 2+ with Fluorescence In Situ Hybridization (FISH) confirmation) as per the American Society of Clinical Oncology/College of American Pathologist (ASCO-CAP) guidelines prior to Screening and confirmed centrally before randomization
- Patients with known HR-ve status (ER-negative and PR-negative) as per local laboratory prior to Screening and confirmed centrally before randomization
- Patient willing to undergo mastectomy or breast-conserving surgery after neoadjuvant therapy
- Patient who completes all necessary baseline laboratory and radiologic investigations prior to randomization as per Schedule of assessment (SoA)
- Patient with baseline left ventricular ejection fraction (LVEF) ≥ 55% measured by echocardiography (ECHO; preferred) or multiple-gated acquisition (MUGA) scan
- Patient is eligible to participant if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
Exclusion Criteria:
- Patients with metastatic or recurrent bilateral breast cancer, or bilateral breast cancer
- Patients with a history of concurrent or previously treated non-breast malignancies. A patient with previous invasive non-breast cancer is eligible provided she has been disease free for more than 5 years
- Patients who have received any previous systemic therapy (including chemotherapy, immunotherapy, HER2-targeted agents, and antitumor vaccines) for treatment or prevention of breast cancer, or radiation therapy for treatment of cancer
- Concurrent anti-cancer treatment in another investigational study, including hormone therapy or immunotherapy
- Major surgical procedure that is unrelated to breast cancer within 4 weeks prior to randomization or from which the patient has not fully recovered
Serious cardiac illness or medical condition including but not limited to the following as per Investigator's discretion:
- Patients with ≥ Class II stage of heart failure as per New York Heart Association Classification
- High risk uncontrolled arrhythmia, such as atrial tachycardia with a heart rate > 100 bpm at rest, significant ventricular arrhythmia (e.g., ventricular tachycardia) required treatment, or higher-grade atrioventricular (AV) block (i.e., Mobitz II second-degree AV block or third-degree AV block)
- History of myocardial infarction or unstable angina pectoris within 1 year of randomization or angina pectoris requiring anti-anginal medication
- Evidence of transmural infarction on ECG
- Clinically significant valvular heart disease
- Poorly controlled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg) in patients on anti-hypertensive medications
- Other concurrent serious diseases that may interfere with study primary endpoint and other study assessments, including, but not limited to, severe pulmonary conditions/illness, active liver disease (for example, active viral hepatitis infection [i.e., hepatitis B or hepatitis C]), autoimmune disorders, history of or known patient of sclerosing cholangitis, or infection with Human immune deficiency virus (HIV)
- Patients with a history of any contraindication to the study treatment regimens
Any of the following abnormal laboratory test results prior to randomization:
- Total bilirubin > upper limit of normal (ULN) or, for cases of known Gilbert's syndrome, total bilirubin > 2 × ULN
- Aspartate aminotransferase and/or alanine aminotransferase > 1.5 × ULN, if considered clinically significant by Investigator
- Alkaline phosphatase >2.5 × ULN, if considered clinically significant by Investigator
- Serum creatinine > 1.5 × ULN
- Creatinine clearance < 60 mL/min
- Total white blood cells count < 2500 cells/μL
- Absolute neutrophil count < 2000 cells/μL
- Platelet count < 100,000 cells/μL
- Participation in any clinical study with an investigational drug, biologic, or device within 1 month prior or within five half-lives (of the drug/ biologic) prior to the enrolment (whichever is longer)
- Have taken any live vaccines 30 days prior to the 1st dose of study treatment
- Any known hypersensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol
- Patients unwilling to follow the study requirements.
Presence of an uncontrolled, unstable, clinically significant medical condition that, in the opinion of the Investigator, may interfere with the interpretation of efficacy and safety parameters or has a medical condition for which the treatment should take precedence over study participation or will interfere with study participation
-
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Treatment Arm B: EU-Perjeta plus trastuzumab, carboplatin and docetaxel
Part 1 (Cycle 1 to 6): Initial loading dose of EU- Perjeta is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: Initial dose of trastuzumab is 8 mg/kg administered as approximately 90-minute IV infusion followed every 3 weeks by 6 mg/kg IV infusion over 30 to 90 minutes Carboplatin: Area under the curve 6 for Cycles 1 to 6 Docetaxel: 75 mg/m2 by IV infusion every 3 weeks for Cycles 1 to 6 Part 2 (Cycle 7 onwards till end of 01 year from Cycle 1 day 1): The patients will be re-randomized (1:1) to receive EU- Perjeta + trastuzumab or PERT-IJS + trastuzumab. Initial loading dose of PERT-IJS is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: As mentioned in part 1 |
EU Perjeta (Pertuzumab) , an antineoplastic agent, is a recombinant humanized monoclonal antibody that specifically targets sub-domain 2 of the extracellular domain of Human Epidermal Growth Factor Receptor 2 (HER2), blocking heterodimerization of HER2 with other members of the receptor family, including epidermal growth factor, Human Epidermal Growth Factor Receptor 3 (HER3) and Human Epidermal Growth Factor Receptor 4 (HER4).
|
Experimental: Treatment Arm A: PERT-IJS plus trastuzumab, carboplatin and docetaxel
Part 1 (Cycle 1 to 6): Initial loading dose of PERT-IJS is 840 mg administered as an approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: Initial dose of trastuzumab is 8 mg/kg administered as approximately 90-minute IV infusion followed every 3 weeks by 6 mg/kg IV infusion over 30 to 90 minutes Carboplatin: Area Under the Curve (AUC) 6 for Cycles 1 to 6 Docetaxel: 75 mg/m2 by IV infusion every 3 weeks for Cycles 1 to 6 Part 2 (Cycle 7 - till end of 1 year from Cycle 1 day 1): Initial loading dose of PERT-IJS is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: As mentioned in part 1 |
PERT-IJS is a monoclonal antibody, which has been developed by Biocon Biologics (earlier in collaboration with Viatris) as a proposed biosimilar to European Union (EU)-approved and United States (US) licensed Perjeta.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy endpoint - Total pathologic complete response between Treatment arm A and Treatment Arm B
Time Frame: Week 18
|
Total pathologic complete response (tpCR; ypT0/Tis,ypN0) in breast and axillary nodes after neoadjuvant treatment by Independent Review Committee (IRC)
|
Week 18
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy endpoint-Total pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
Time Frame: Week 18
|
Total pathologic complete response (tpCR; ypT0/Tis, ypN0) in breast and axillary nodes after neoadjuvant treatment by local histopathologist
|
Week 18
|
Efficacy endpoint: Pathologic complete response between Treatment Arm A and Treatment Arm B
Time Frame: Week 18
|
Pathologic complete response (pCR; ypT0/ypN0) after neoadjuvant treatment by IRC and local histopathologist
|
Week 18
|
Efficacy endpoint-Objective response rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
Time Frame: Week 18
|
Objective response rate (ORR) after neoadjuvant treatment in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
|
Week 18
|
Efficacy endpoint-Event free survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
Time Frame: Week 18
|
Event free survival (EFS) rate
|
Week 18
|
Efficacy endpoint- Overall survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
Time Frame: Week 18
|
Overall survival (OS) rate
|
Week 18
|
Efficacy endpoint-EFS rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
Time Frame: 1 Year
|
EFS rate
|
1 Year
|
Efficacy endpoint - Overall Survival rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
Time Frame: 1 Year
|
Overall survival rate
|
1 Year
|
Efficacy endpoint - Overall Response Rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
Time Frame: 1 Year
|
Overall Response Rate
|
1 Year
|
Efficacy Endpoint: EFS rate after the single switch from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on Treatment B
Time Frame: 1 year
|
EFS rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab
|
1 year
|
Efficacy Endpoint: Disease free survival rate after the single switch from from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on EU-Perjeta+trastuzumab
Time Frame: 1 year
|
Disease free survival (DFS) rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
|
1 year
|
Efficacy Endpoint: Overall survival rate after the single switch from from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on EU-Perjeta+trastuzumab
Time Frame: 1 year
|
OS rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
|
1 year
|
Safety Endpoint: treatment-emergent adverse events and serious adverse events
Time Frame: week 18
|
Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
|
week 18
|
Safety Endpoint: left ventricular ejection fraction
Time Frame: week 18
|
Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
|
week 18
|
Safety Endpoint: Vital signs
Time Frame: week 18
|
Number of subjects with clinically significant changes in Vital signs
|
week 18
|
Safety Endpoint-ECG PR Interval
Time Frame: week 18
|
Number of subjects with clinically significant changes in ECG PR Interval
|
week 18
|
Safety Endpoint-ECG QRS Interval
Time Frame: week 18
|
Number of subjects with clinically significant changes in ECG QRS Interval
|
week 18
|
Safety Endpoint-ECG QT Interval
Time Frame: week 18
|
Number of subjects with clinically significant changes in ECG QT Interval
|
week 18
|
Safety Endpoint-clinical laboratory assessments
Time Frame: week 18
|
Number of subjects with clinically significant changes in Clinical laboratory assessments
|
week 18
|
Safety Endpoint-pregnancy test
Time Frame: week 18
|
Number of subjects with Pregnancy outcome
|
week 18
|
Safety Endpoint-physical examination
Time Frame: week 18
|
Number of subjects with clinically significant changes in Physical examination
|
week 18
|
Safety Endpoint: treatment-emergent adverse events and serious adverse events of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta
Time Frame: 1 year
|
Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
|
1 year
|
Safety Endpoint: left ventricular ejection fraction of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
Time Frame: 1 year
|
Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
|
1 year
|
Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS -throughout compared to patients randomized to EU-Perjeta throughout- Vital signs
Time Frame: 1 year
|
Number of subjects with clinically significant changes in Vital signs
|
1 year
|
Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG PR Interval
Time Frame: 1 year
|
Number of subjects with clinically significant changes in ECG PR Interval
|
1 year
|
Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QRS Interval
Time Frame: 1 year
|
Number of subjects with clinically significant changes in ECG QRS Interval
|
1 year
|
Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QT Interval
Time Frame: 1 year
|
Number of subjects with clinically significant changes in ECG QT Interval
|
1 year
|
Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG QTc Interval
Time Frame: 1 year
|
Number of subjects with clinically significant changes in ECG QTc Interval
|
1 year
|
Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Clinical laboratory assessments
Time Frame: 1 year
|
Number of subjects with clinically significant changes in Clinical laboratory assessments
|
1 year
|
Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- Pregnancy test
Time Frame: 1 year
|
Number of subjects with Pregnancy outcome
|
1 year
|
Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Physical examination
Time Frame: 1 year
|
Number of subjects with clinically significant changes in Physical examination
|
1 year
|
Safety Endpoint: Incidence of TEAEs and SAEs after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab throughout
Time Frame: 1 Year
|
Incidence of TEAEs and SAEs after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
|
1 Year
|
Immunogenicity End Point: after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab
Time Frame: 1 Year
|
Immunogenicity (ADA titer and nAb titer) after switching of treatment from EU-Perjeta to PERT-IJS plus trastuzumab versus those continuing on EU-Perjeta + trastuzumab
|
1 Year
|
Pharmacokinetic (PK) endpoint-The trough serum concentration
Time Frame: 1 Year
|
The trough serum concentration (Ctrough)
|
1 Year
|
Efficacy endpoint- Breast pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
Time Frame: Week 18
|
Breast pathologic complete response (bpCR; ypT0/Tis) after neoadjuvant treatment by IRC and local histopathologist
|
Week 18
|
Safety Endpoint- ECG corrected QT interval (QTc) Interval
Time Frame: week 18
|
Number of subjects with clinically significant changes in ECG QTc Interval
|
week 18
|
Immunogenicity Endpoint
Time Frame: week 18
|
Immunogenicity (anti-drug antibodies (ADA) and neutralizing antibodies (nAb) titers)
|
week 18
|
Immunogenicity Endpoint of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
Time Frame: 1 year
|
Immunogenicity (anti-drug antibodies (ADA) and neutralizing antibodies (nAb) titers)
|
1 year
|
Safety End Point :left ventricular ejection fraction incidences after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab
Time Frame: 1 year
|
Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
|
1 year
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BIO-PERTUZ-301
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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