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
Red color represents old content. It may be empty showing addition in the new version.
Green color represents new content. It may be empty showing deletion in the new version.
Inline
Side by side
Added new contents,
deleted old contents,contents that are not changed.
New table contents
New table contents
Old table contents
Old table contents
Unchanged contents
Unchanged contents
Added new contents, contents that are not changed.
Deleted old contents, contents that are not changed.
Old table contents
Old table contents
Unchanged contents
Unchanged contents
New table contents
New table contents
Unchanged contents
Unchanged contents
Ethics committees
#1
IR.TUMS.VCR.REC.1397.4973
IR.TUMS.VCR.REC.1397.127
IR.TUMS.VCR.REC.1397.4973IR.TUMS.VCR.REC.1397.127
Protocol summary
Study aim
efficacy and safety of Pertuzumab® (CinnaGen) compared with Perjeta® (Genentech) in neoadjuvant treatment of HER2+ breast cancer patients
Design
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.
Settings and conduct
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.
Participants/Inclusion and exclusion criteria
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
Intervention groups
A: Pertuzumab(CinnaGen) with Trastuzumab, Docetaxel and Carboplatin
B: Perjeta(Genentech) with Trastuzumab, Docetaxel and Carboplatin
Main outcome variables
pathologic complete response
General information
Reason for update
Protocol Amendment
Acronym
IRCT registration information
IRCT registration number:IRCT20150303021315N11
Registration date:2018-06-11, 1397/03/21
Registration timing:registered_while_recruiting
Last update:2020-04-18, 1399/01/30
Update count:4
Registration date
2018-06-11, 1397/03/21
Registrant information
Name
Nassim Anjidani
Name of organization / entity
Orchid Pharmed
Country
Iran (Islamic Republic of)
Phone
+98 21 4347 3000
Email address
amini@orchidpharmed.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2018-05-22, 1397/03/01
Expected recruitment end date
2019-11-22, 1398/09/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
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
Public title
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)
Purpose
Treatment
Inclusion/Exclusion criteria
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
Age
From 18 years old to 70 years old
Gender
Female
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
214
Randomization (investigator's opinion)
Randomized
Randomization description
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.
Blinding (investigator's opinion)
Triple blinded
Blinding description
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.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Guilan University of Medical Sciences
Street address
opposite 17 Shahrivar Hospital, Shahid siadati St. , Namjou St. , Rasht
City
Rasht
Province
Guilan
Postal code
41446-66949
Approval date
2018-01-27, 1396/11/07
Ethics committee reference number
IR.GUMS.REC1395.444
2
Ethics committee
Name of ethics committee
Research Ethics Committee of Tehran University of Medical Sciences
Street address
Sixth floor, Research Deputy of Tehran University of Medical Sciences, Ghods Street, Keshavarz Boulvard
City
Tehran
Province
Tehran
Postal code
1417653761
Approval date
2018-04-18, 1397/01/29
Ethics committee reference number
IR.TUMS.VCR.REC.1397.127
Health conditions studied
1
Description of health condition studied
Breast cancer
ICD-10 code
C50.9
ICD-10 code description
Malignant neoplasm of breast of unspecified site
Primary outcomes
1
Description
Pathologic Complete Response
Timepoint
before intervention and 3-5 weeks After last intervention
Method of measurement
Pathology laboratory
Secondary outcomes
1
Description
Clinical response rate
Timepoint
before intervention and 3 weeks after last intervention
Method of measurement
Physical examination and imaging (MRI)
2
Description
Rate of breast-conserving surgery
Timepoint
3-5 weeks after last intervention
Method of measurement
Physician report
3
Description
Safety
Timepoint
Every 3 weeks
Method of measurement
Patient’s history and laboratory data
4
Description
Immunogenicity
Timepoint
Every 3 weeks
Method of measurement
Blood test and antidrug antibody presence evaluating
5
Description
total pathological complete response in breast and axillary lymph nodes
Timepoint
3-5 weeks After last intervention
Method of measurement
Pathology laboratory
Intervention groups
1
Description
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.
Category
Treatment - Drugs
2
Description
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.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Mehrad Hospital
Full name of responsible person
Dr. Jahangir Raafat
Street address
Mir Emad St.,Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1587963110
Phone
+98 21 8874 7401
Email
jahangirraafat@yahoo.com
2
Recruitment center
Name of recruitment center
Jahad daneshgahi center
Full name of responsible person
Dr. Safa Najjar Najafi
Street address
No. 45, West nazari St., Aboureyhan St.,Tehran, iran