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Comparing Efficacy and Safety Between Pertuzumab® and Perjeta® in Neoadjuvant Treatment of HER2+ Breast Cancer

Primary Purpose

HER2-positive Breast Cancer

Status
Completed
Phase
Phase 3
Locations
Iran, Islamic Republic of
Study Type
Interventional
Intervention
Trastuzumab
Pertuzumab
Carboplatin
Docetaxel
Sponsored by
Cinnagen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HER2-positive Breast Cancer focused on measuring Pertuzumab, HER2-positive Breast Cancer, Neoadjuvant treatment, Equivalency clinical trial

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Female patients aged 18-70 years.
  • Diagnosed with locally advanced (T2-3, N2-3, M0 or T4a-c, any N, M0), inflammatory (T4d, any N, M0) or operable (T2-3, N0-1, M0), invasive breast cancer.
  • Primary tumor > 2 cm in diameter.
  • HER2 positive breast cancer confirmed (Tumors must be IHC 3+ or FISH/CISH + for IHC 2+ tumors).
  • Baseline LVEF ≥ 55% measured by echocardiography.
  • Performance status ECOG ≤ 1
  • Signed informed consent.

Exclusion Criteria:

  • Metastatic disease (Stage IV) or bilateral breast cancer.
  • Previous anticancer therapy or radiotherapy for any malignancy.
  • Other malignancy, except for carcinoma in situ of the cervix or basal cell carcinoma.
  • Received any investigational treatment within 4 weeks of study start.
  • At least 4 weeks since major surgery.
  • Uncontrolled hypertension (systolic > 150 and/or diastolic > 100), unstable angina, CHF of any NYHA classification, serious cardiac arrhythmia requiring treatment, history of myocardial infarction within 6 months of enrollment.

  • Hematological, biochemical and organ dysfunction:

    1. Inadequate bone marrow function: Absolute Neutrophil Count (ANC) < 1500 cells/ µL, Platelet count < 100,000 cells/ µL and Hb < 9 g/dL).
    2. Impaired liver function: serum [total] bilirubin > 1.25 x ULN, AST/ALT > 1. 5 x ULN with ALP > 2.5 x ULN
    3. Inadequate renal function: serum creatinine > 1.5 x ULN.
  • Dyspnea at rest or other diseases which require continuous oxygen therapy.
  • Severe uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, metabolic, etc).
  • Current chronic daily treatment with corticosteroids (dose of ≥10 mg Oral prednisolone, or equivalent [excluding inhaled steroids])
  • Subjects with known infection with HIV, HBV, and HCV.
  • Known hypersensitivity to any of the study drugs or excipients.
  • Pregnant and/or lactating women or subjects with reproductive potential not willing to use effective methods of contraception.
  • Subjects assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol (e.g.: physical, psychological and mental problems)

Sites / Locations

  • Besat Clinic
  • Dr. Behrouz Najafi's office
  • Dr. Mehdi Mirblouk's office
  • Razi Hospital
  • Dr. Aboulqasem Allahyari's office
  • Imam Reza Hospital
  • Qaem Hospital
  • Sanabad Hospital
  • Arvand Hospital
  • Baqaei Hospital
  • Shafa Hospital
  • Milad Hospital
  • Saba Clinic
  • Seyed-Al-Shohada Hospital
  • Sheikh Mofid Clinic
  • Dr. Mehrdad Payende's office
  • Dr. Behjat Kalantari's office
  • Javad-Al-Aemeh Clinic
  • Shahid Bahonar Hospital
  • Amir Hospital
  • Namazi Hospital
  • Shahid Faghihi Hospital
  • Shams Hospital
  • Baqiatallah Hospital
  • BuoAli Hospital
  • Dr. Safa Najjar Najafi's office
  • Ebn-Sina Hospital
  • Firoozgar Hospital
  • Imam Khomeini Hospital
  • Iran-Mehr Hospital
  • Jam Hospital
  • Jihad University Clinic
  • Masih Daneshvari Hospital
  • Massoud Clinic
  • Mehrad Hospital
  • Naft Hospital
  • Rasool Akram Hospital
  • Resalat Hospital
  • Sajjad Hospital
  • Sina Hospital
  • Taleghani Hospital
  • Tehran Hospital
  • Toos Hospital
  • Dr.Mortazavizadeh's office

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

TCHP regimen (trastuzumab, pertuzumab® (CinnaGen Co.), carboplatin, and docetaxel)

TCHP regimen (trastuzumab, Perjeta®, carboplatin, and docetaxel)

Arm Description

Study drugs are administered intravenously on a 3-weekly schedule and given consecutively on the same day in the following sequence: trastuzumab, followed by pertuzumab, carboplatin, and docetaxel. Trastuzumab is given at an initial dose of 8 mg/kg, followed by 6 mg/kg; pertuzumab® (CinnaGen Co.) is given at an initial dose of 840 mg, followed by 420 mg. Carboplatin is administered at a dose of AUC6 (area under the plasma concentration-time curve) and docetaxel is given at 75 mg/m2.

Study drugs are administered intravenously on a 3-weekly schedule and given consecutively on the same day in the following sequence: trastuzumab, followed by pertuzumab, carboplatin, and docetaxel. Trastuzumab is given at an initial dose of 8 mg/kg, followed by 6 mg/kg; Perjeta® is given at an initial dose of 840 mg, followed by 420 mg. Carboplatin is administered at a dose of AUC6 (area under the plasma concentration-time curve) and docetaxel is given at 75 mg/m2.

Outcomes

Primary Outcome Measures

Breast Pathological Complete Response (bpCR)
bpCR defined as the absence of invasive neoplastic cells in the breast at microscopic examination of the primary tumor at surgery following primary systemic therapy (ypT0/is)

Secondary Outcome Measures

Total Pathological Complete Response (tpCR)
tpCR defined as no invasive tumor residues in the breast and lymph nodes (ypT0/is ypN0)
Objective response rate (ORR)
ORR defined as the proportion of patients who achieved a complete or partial response
Rate of breast-conserving surgery (BCS)
Rate of BCS for patients for whom mastectomy was planned before treatment (T2-3)
Adverse Events (AEs)
AEs were monitored continuously and all the reported events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 . The causality relation was assessed based on World Health Organization (WHO) criteria.
Abnormal laboratory data
The abnormality in selected laboratory data was considered as adverse event and was reported.
Decline in LVEF of ≥10% points from baseline to <50%
LVEF decrease was measured by echocardiography.
Incidence of symptomatic left ventricular systolic dysfunction (LVSD)
symptoms of LVSD were monitored by physician and reported as AEs.
Immunogenicity
antidrug antibody [ADA] assessment

Full Information

First Posted
June 22, 2021
Last Updated
August 31, 2021
Sponsor
Cinnagen
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1. Study Identification

Unique Protocol Identification Number
NCT04957212
Brief Title
Comparing Efficacy and Safety Between Pertuzumab® and Perjeta® in Neoadjuvant Treatment of HER2+ Breast Cancer
Official Title
A Phase III, Randomized, Two-armed, Parallel, Triple-blind, Active-controlled, Equivalency Clinical Trial of Efficacy and Safety Pertuzumab® (CinnaGen Co.) Compared With Perjeta® (Originator Pertuzumab) in Neoadjuvant Treatment of HER2+ Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
August 11, 2018 (Actual)
Primary Completion Date
May 27, 2020 (Actual)
Study Completion Date
May 27, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cinnagen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
This study was a phase III, multicenter, triple-blind, equivalency clinical trial to determine the therapeutic efficacy and safety between Pertuzumab® (CinnaGen Co.) compared to originator pertuzumab in HER2-positive early breast cancer patients. Patients were stratified dynamically for random assignment to treatment with either Pertuzumab® (CinnaGen Co.) or originator pertuzumab, and received neoadjuvant TCHP regimen every 3- weeks.
Detailed Description
This study was a phase III, multicenter, triple-blind , equivalency clinical trial to determine the therapeutic efficacy and safety between Pertuzumab® (CinnaGen Co.) compared to originator pertuzumab in HER2-positive early breast cancer patients. Patients stratified dynamically according to two factors: type of breast cancer (inflammatory, locally and operable) and estrogen/ progesterone receptor (ER/PR) (positive or negative) with 1:1 allocation ratio. Study drugs were administered intravenously on a 3-weekly schedule and were given consecutively on the same day in the following sequence: trastuzumab, followed by pertuzumab, carboplatin, and docetaxel (TCHP regimen). The primary endpoint was breast pCR (bpCR). Secondary efficacy endpoints included total pCR (tpCR); objective response rate (ORR) and rate of breast-conserving surgery (BCS) for patients for whom mastectomy was planned before treatment (T2-3). During this study, adverse events (AEs) were monitored continuously. As an adverse event of special interest (AESI), left ventricular ejection fraction (LVEF) decreased was monitored and assessed by echocardiography throughout the study. Immunogenicity was also assessed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2-positive Breast Cancer
Keywords
Pertuzumab, HER2-positive Breast Cancer, Neoadjuvant treatment, Equivalency clinical trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Patients were randomly assigned to treatment by a central randomization procedure via telephone call for each consecutive eligible patient. Randomization codes were allocated after all eligibility criteria were approved, stratification factors were identified and the informed consent form was signed. After randomization procedure, a code was allocated to each patient that was used as patient identifier throughout the study. The assigned code was denoted by 4 initials (corresponding to the 2 first letter of the first name, the 2 first letter of the first surname) and 3 numbers (center code).
Allocation
Randomized
Enrollment
214 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TCHP regimen (trastuzumab, pertuzumab® (CinnaGen Co.), carboplatin, and docetaxel)
Arm Type
Experimental
Arm Description
Study drugs are administered intravenously on a 3-weekly schedule and given consecutively on the same day in the following sequence: trastuzumab, followed by pertuzumab, carboplatin, and docetaxel. Trastuzumab is given at an initial dose of 8 mg/kg, followed by 6 mg/kg; pertuzumab® (CinnaGen Co.) is given at an initial dose of 840 mg, followed by 420 mg. Carboplatin is administered at a dose of AUC6 (area under the plasma concentration-time curve) and docetaxel is given at 75 mg/m2.
Arm Title
TCHP regimen (trastuzumab, Perjeta®, carboplatin, and docetaxel)
Arm Type
Active Comparator
Arm Description
Study drugs are administered intravenously on a 3-weekly schedule and given consecutively on the same day in the following sequence: trastuzumab, followed by pertuzumab, carboplatin, and docetaxel. Trastuzumab is given at an initial dose of 8 mg/kg, followed by 6 mg/kg; Perjeta® is given at an initial dose of 840 mg, followed by 420 mg. Carboplatin is administered at a dose of AUC6 (area under the plasma concentration-time curve) and docetaxel is given at 75 mg/m2.
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Intervention Description
An initial dose of 8 mg/kg, followed by 6 mg/kg every 3-weeks
Intervention Type
Drug
Intervention Name(s)
Pertuzumab
Intervention Description
An initial dose of 840 mg, followed by 420 mg every 3-weeks
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
A dose of AUC6 (area under the plasma concentration-time curve) every 3-weeks
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
75 mg/m2 every 3-weeks
Primary Outcome Measure Information:
Title
Breast Pathological Complete Response (bpCR)
Description
bpCR defined as the absence of invasive neoplastic cells in the breast at microscopic examination of the primary tumor at surgery following primary systemic therapy (ypT0/is)
Time Frame
18-20 weeks after first intervention
Secondary Outcome Measure Information:
Title
Total Pathological Complete Response (tpCR)
Description
tpCR defined as no invasive tumor residues in the breast and lymph nodes (ypT0/is ypN0)
Time Frame
18-20 weeks after first intervention
Title
Objective response rate (ORR)
Description
ORR defined as the proportion of patients who achieved a complete or partial response
Time Frame
18-20 weeks after first intervention
Title
Rate of breast-conserving surgery (BCS)
Description
Rate of BCS for patients for whom mastectomy was planned before treatment (T2-3)
Time Frame
18-20 weeks after first intervention
Title
Adverse Events (AEs)
Description
AEs were monitored continuously and all the reported events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 . The causality relation was assessed based on World Health Organization (WHO) criteria.
Time Frame
Throughout the study duration (from first visit to week 18-20)
Title
Abnormal laboratory data
Description
The abnormality in selected laboratory data was considered as adverse event and was reported.
Time Frame
Throughout the study duration (from first visit to week 18-20)
Title
Decline in LVEF of ≥10% points from baseline to <50%
Description
LVEF decrease was measured by echocardiography.
Time Frame
every 6 week (from first visit to week 18-20)
Title
Incidence of symptomatic left ventricular systolic dysfunction (LVSD)
Description
symptoms of LVSD were monitored by physician and reported as AEs.
Time Frame
Throughout the study duration (from first visit to week 18-20)
Title
Immunogenicity
Description
antidrug antibody [ADA] assessment
Time Frame
Every 3 weeks (from first intervention to week 18)

10. Eligibility

Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female patients aged 18-70 years. Diagnosed with locally advanced (T2-3, N2-3, M0 or T4a-c, any N, M0), inflammatory (T4d, any N, M0) or operable (T2-3, N0-1, M0), invasive breast cancer. Primary tumor > 2 cm in diameter. HER2 positive breast cancer confirmed (Tumors must be IHC 3+ or FISH/CISH + for IHC 2+ tumors). Baseline LVEF ≥ 55% measured by echocardiography. Performance status ECOG ≤ 1 Signed informed consent. Exclusion Criteria: Metastatic disease (Stage IV) or bilateral breast cancer. Previous anticancer therapy or radiotherapy for any malignancy. Other malignancy, except for carcinoma in situ of the cervix or basal cell carcinoma. Received any investigational treatment within 4 weeks of study start. At least 4 weeks since major surgery. Uncontrolled hypertension (systolic > 150 and/or diastolic > 100), unstable angina, CHF of any NYHA classification, serious cardiac arrhythmia requiring treatment, history of myocardial infarction within 6 months of enrollment. Hematological, biochemical and organ dysfunction: Inadequate bone marrow function: Absolute Neutrophil Count (ANC) < 1500 cells/ µL, Platelet count < 100,000 cells/ µL and Hb < 9 g/dL). Impaired liver function: serum [total] bilirubin > 1.25 x ULN, AST/ALT > 1. 5 x ULN with ALP > 2.5 x ULN Inadequate renal function: serum creatinine > 1.5 x ULN. Dyspnea at rest or other diseases which require continuous oxygen therapy. Severe uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, metabolic, etc). Current chronic daily treatment with corticosteroids (dose of ≥10 mg Oral prednisolone, or equivalent [excluding inhaled steroids]) Subjects with known infection with HIV, HBV, and HCV. Known hypersensitivity to any of the study drugs or excipients. Pregnant and/or lactating women or subjects with reproductive potential not willing to use effective methods of contraception. Subjects assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol (e.g.: physical, psychological and mental problems)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Behrouz Najafi, AssistantProfessor
Organizational Affiliation
Assistant Professor of Hematology and Oncology Research Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Besat Clinic
City
Rasht
State/Province
Guilan
Country
Iran, Islamic Republic of
Facility Name
Dr. Behrouz Najafi's office
City
Rasht
State/Province
Guilan
Country
Iran, Islamic Republic of
Facility Name
Dr. Mehdi Mirblouk's office
City
Rasht
State/Province
Guilan
Country
Iran, Islamic Republic of
Facility Name
Razi Hospital
City
Rasht
State/Province
Guilan
Country
Iran, Islamic Republic of
Facility Name
Dr. Aboulqasem Allahyari's office
City
Mashhad
State/Province
Khorasan Razavi
Country
Iran, Islamic Republic of
Facility Name
Imam Reza Hospital
City
Mashhad
State/Province
Khorasan Razavi
Country
Iran, Islamic Republic of
Facility Name
Qaem Hospital
City
Mashhad
State/Province
Khorasan Razavi
Country
Iran, Islamic Republic of
Facility Name
Sanabad Hospital
City
Mashhad
State/Province
Khorasan Razavi
Country
Iran, Islamic Republic of
Facility Name
Arvand Hospital
City
Ahvaz
State/Province
Khozestan
Country
Iran, Islamic Republic of
Facility Name
Baqaei Hospital
City
Ahvaz
State/Province
Khozestan
Country
Iran, Islamic Republic of
Facility Name
Shafa Hospital
City
Ahvaz
State/Province
Khozestan
Country
Iran, Islamic Republic of
Facility Name
Milad Hospital
City
Isfahan
Country
Iran, Islamic Republic of
Facility Name
Saba Clinic
City
Isfahan
Country
Iran, Islamic Republic of
Facility Name
Seyed-Al-Shohada Hospital
City
Isfahan
Country
Iran, Islamic Republic of
Facility Name
Sheikh Mofid Clinic
City
Isfahan
Country
Iran, Islamic Republic of
Facility Name
Dr. Mehrdad Payende's office
City
Kermanshah
Country
Iran, Islamic Republic of
Facility Name
Dr. Behjat Kalantari's office
City
Kerman
Country
Iran, Islamic Republic of
Facility Name
Javad-Al-Aemeh Clinic
City
Kerman
Country
Iran, Islamic Republic of
Facility Name
Shahid Bahonar Hospital
City
Kerman
Country
Iran, Islamic Republic of
Facility Name
Amir Hospital
City
Shiraz
Country
Iran, Islamic Republic of
Facility Name
Namazi Hospital
City
Shiraz
Country
Iran, Islamic Republic of
Facility Name
Shahid Faghihi Hospital
City
Shiraz
Country
Iran, Islamic Republic of
Facility Name
Shams Hospital
City
Tabriz
Country
Iran, Islamic Republic of
Facility Name
Baqiatallah Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
BuoAli Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Dr. Safa Najjar Najafi's office
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Ebn-Sina Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Firoozgar Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Imam Khomeini Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Iran-Mehr Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Jam Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Jihad University Clinic
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Masih Daneshvari Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Massoud Clinic
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Mehrad Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Naft Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Rasool Akram Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Resalat Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Sajjad Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Sina Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Taleghani Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Tehran Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Toos Hospital
City
Tehran
Country
Iran, Islamic Republic of
Facility Name
Dr.Mortazavizadeh's office
City
Yazd
Country
Iran, Islamic Republic of

12. IPD Sharing Statement

Learn more about this trial

Comparing Efficacy and Safety Between Pertuzumab® and Perjeta® in Neoadjuvant Treatment of HER2+ Breast Cancer

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