Protocol summary
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Study aim
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efficacy and safety of Pertuzumab® (CinnaGen) compared with Perjeta® (Genentech) in neoadjuvant treatment of HER2+ breast cancer patients
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Design
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after referral to the researchers, in the case of having informed consent will receive a randomization code, and randomly enter in to one of the two groups of pertuzumab and will receive their regimen and they will be evaluated.
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Settings and conduct
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All drugs are in the same boxes and vials,there is no apparent difference between the Iranian drug and the brand, and the researchers, patients and the data analyzing team will be completely unaware of the type of the drug.
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Participants/Inclusion and exclusion criteria
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Inclusion: Female aged 18 -70 ; Operable, locally advanced,inflammatory breast cancer; primary tumor size >2 cm; HER2+; ECOG 0-1, LVEF ≥55%
Exclusion: Metastatic (stage IV) or bilateral breast cancer;Previous systemic or local anticancer therapy;other malignancy except for carcinoma in situ of cervix, basal cell carcinoma, or squamous cell carcinoma of skin; Use of another research drug in the four weeks before study;Major surgery four weeks before study; Uncontrolled hypertension; unstable angina, congestive heart failure, serious cardiac arrhythmia needs treatment,myocardial infarction within 6 months of enrollment, Inadequate bone marrow, liver, or renal function; Shortness of breath during rest or any other disease that requires continuous oxygen therapy, any severe uncontrolled systemic disease; Chronic treatment with corticosteroids; HIV,HBV,HCV infections, Hypersensitivity to studied drugs or excipients; Pregnant, lactating; Unwillingness or inability to fulfill the protocol
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Intervention groups
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A: Pertuzumab(CinnaGen) with Trastuzumab, Docetaxel and Carboplatin
B: Perjeta(Genentech) with Trastuzumab, Docetaxel and Carboplatin
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Main outcome variables
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pathologic complete response
General information
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Reason for update
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Protocol Amendment
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20150303021315N11
Registration date:
2018-06-11, 1397/03/21
Registration timing:
prospective
Last update:
2022-02-14, 1400/11/25
Update count:
4
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Registration date
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2018-06-11, 1397/03/21
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2018-05-22, 1397/03/01
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Expected recruitment end date
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2019-11-22, 1398/09/01
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Actual recruitment start date
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2018-08-05, 1397/05/14
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Actual recruitment end date
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2019-12-12, 1398/09/21
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Trial completion date
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2020-05-20, 1399/02/31
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Scientific title
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A Phase III, randomized, two armed, parallel, triple-blind, active controlled, equivalency clinical trial to determine the therapeutic efficacy and safety between Pertuzumab® (produced by CinnaGen Co.) plus Trastuzumab, Carboplatin and Docetaxel compared with Perjeta® (Pertuzumab, the reference drug, produced by Roche Company) plus Trastuzumab, Carboplatin and Docetaxel in neoadjuvant treatment of HER 2 positive Breast Cancer patients
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Public title
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Equivalency clinical trial to determine the therapeutic efficacy and safety between Pertuzumab® (produced by CinnaGen Co.) compared with Perjeta® (Pertuzumab, the reference drug, produced by Roche Company)
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Female patients aged 18 - 70
Operable (T2-3, N0-1, M0), locally advanced (T2-3, N2 or N3, M0; T4a-c, any N, M0), or inflammatory (T4d, any N, M0) breast cancer
Primary tumor diameter should be more than 2 centimeters
Positive HER2 status approved by immunohistochemistry (IHC 3+ or IHC 2+ verified by fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH))
Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
LVEF ≥55% at baseline assessed by echocardiography
Able and willing to sign an informed consent
Exclusion criteria:
Metastatic (stage IV) or bilateral breast cancer
Previous systemic or local anticancer therapy for any cancer
Any other malignancy except for carcinoma in situ of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin
Use of another research drug in the four weeks before the start of the study
Major surgery four weeks before the start of the study
Uncontrolled hypertension (systolic blood pressure more than 150 mmHg or/and diastolic blood pressure more than 100 mmHg)
Inadequate bone marrow, liver, or renal function:ANC < 1500/µLPlt < 100,000/µLHb< 9 g/dLALT/AST > 1.5 ULN (upper limit of normal)ALP > 2.5 ULNTotal serum bilirubin > 1.25 ULNSerum creatinine > 1.5 ULN
Shortness of breath during rest or any other disease that requires continuous oxygen therapy
Any severe uncontrolled systemic disease (cardiovascular, pulmonary, metabolic, etc.)
Chronic treatment with corticosteroids with a daily dose of ≥ 10 mg oral prednisolone or equivalent of other types (other than inhaled corticosteroid drugs)
Patients with HIV, HBV, and HCV infections
Hypersensitivity to any of the studied drugs or excipients
Pregnant, lactating or fertile women who do not want to use contraceptive methods (contraceptives should be taken in to consideration up to six months after the last dose of the drug)
Unwillingness or inability to fulfill the requirements of the protocol, including any kind of condition (physical, mental or social) that affects one's ability to fulfill the requirements of the protocol
unstable angina
congestive heart failure of any class of NYHA (New York Heart Association)
serious cardiac arrhythmia needs treatment
history of myocardial infarction within 6 months prior to enrollment
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Age
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From 18 years old to 70 years old
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Gender
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Female
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Phase
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3
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Groups that have been masked
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No information
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Sample size
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Target sample size:
214
Actual sample size reached:
214
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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Eligible patients will be assigned to groups using dynamic randomization, according to these variables:
1- ER/PR: ER/PR+, ER/PR-
2- Type of breast cancer: operable, locally advanced, inflammatory
After randomization procedure, a code will be allocated to each patient that will be used as patient identifier throughout the study. The assigned code will be denoted by 4 initials (corresponding to the first two letters of first name, first two letters of surname) and 4 numbers (center code). Moreover, the described code is followed by study unique identification code consisting of first two letters of the generic name of the investigational product and study phase number, respectively (PE3), and four numbers (corresponding to the randomization number), e.g. ABCD0001PE3-0001. The randomization number will be assigned in a consecutive way, e.g. 0001, 0002, 0003 and so on until the last.
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Blinding (investigator's opinion)
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Triple blinded
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Blinding description
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To prevent the influence of knowing intervention group on study conclusion, the subjects and those who assess the study outcomes will be blinded. For this purpose, subjects and administrator of drug will be blinded by using a similar masked vials.
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2018-01-27, 1396/11/07
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Ethics committee reference number
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IR.GUMS.REC1395.444
2
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Ethics committee
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Approval date
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2018-04-18, 1397/01/29
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Ethics committee reference number
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IR.TUMS.VCR.REC.1397.127
Health conditions studied
1
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Description of health condition studied
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Breast cancer
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ICD-10 code
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C50.9
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ICD-10 code description
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Malignant neoplasm of breast of unspecified site
Primary outcomes
1
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Description
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Pathologic Complete Response
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Timepoint
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before intervention and 3-5 weeks After last intervention
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Method of measurement
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Pathology laboratory
Secondary outcomes
1
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Description
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Clinical response rate
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Timepoint
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before intervention and 3 weeks after last intervention
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Method of measurement
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Physical examination and imaging (MRI)
2
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Description
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Rate of breast-conserving surgery
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Timepoint
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3-5 weeks after last intervention
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Method of measurement
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Physician report
3
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Description
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Safety
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Timepoint
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Every 3 weeks
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Method of measurement
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Patient’s history and laboratory data
4
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Description
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Immunogenicity
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Timepoint
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Every 3 weeks
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Method of measurement
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Blood test and antidrug antibody presence evaluating
5
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Description
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total pathological complete response in breast and axillary lymph nodes
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Timepoint
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3-5 weeks After last intervention
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Method of measurement
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Pathology laboratory
Intervention groups
1
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Description
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Intervention group: Study drugs are administered intravenously on a 3-weekly schedule for 6 cycles, and given consecutively on the same day in the following sequence: trastuzumab, followed by pertuzumab (cinnagen), carboplatin, and docetaxel. Trastuzumab is given at an initial dose of 8 mg/kg, followed by 6 mg/kg; pertuzumab is given at an initial dose of 840 mg, followed by 420 mg.
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Category
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Treatment - Drugs
2
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Description
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Control group: Control group: Study drugs are administered intravenously on a 3-weekly schedule for 6 cycles, and given consecutively on the same day in the following sequence: trastuzumab, followed by pertuzumab (Perjeta) , carboplatin, and docetaxel. Trastuzumab is given at an initial dose of 8 mg/kg, followed by 6 mg/kg; Perjeta® in group B is given at an initial dose of 840 mg, followed by 420 mg.
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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CinnaGen company
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Proportion provided by this source
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100
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Industry
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Undecided - It is not yet known if there will be a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available