Clinical trial NCT04957212: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: HER2-positive Breast Cancer
Keywords: Pertuzumab
HER2-positive Breast Cancer
Neoadjuvant treatment
Equivalency clinical trial
Lead sponsor: Cinnagen
Sponsor class: INDUSTRY
First posted: 2021-07-12
Enrollment: 214
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

  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)

Primary outcomes:
measure: Breast Pathological Complete Response (bpCR)
timeFrame: 18-20 weeks after first intervention
Secondary outcomes:
measure: Total Pathological Complete Response (tpCR)
timeFrame: 18-20 weeks after first intervention
measure: Objective Response Rate (ORR)
timeFrame: 18-20 weeks after first intervention
measure: Rate of Breast-conserving Surgery (BCS)
timeFrame: 18-20 weeks after first intervention
measure: Safety Assessment Including Treatment Related Adverse Events
timeFrame: Throughout the study duration (from first visit to week 18-20)
measure: Abnormal Laboratory Data
timeFrame: Throughout the study duration (from first visit to week 18-20)
measure: Decrease in Left Ventricular Ejection Fraction (LVEF)
timeFrame: every 6 week (from first visit to week 18-20)
measure: Incidence of Symptomatic Left Ventricular Systolic Dysfunction (LVSD)
timeFrame: Throughout the study duration (from first visit to week 18-20)
measure: Immunogenicity
timeFrame: Every 3 weeks (from first intervention to week 18)
Other outcomes:
Locations:
city: Rasht
country: Iran, Islamic Republic of
facility: Besat Clinic
state: Guilan
city: Rasht
country: Iran, Islamic Republic of
facility: Dr. Behrouz Najafi's office
state: Guilan
city: Rasht
country: Iran, Islamic Republic of
facility: Dr. Mehdi Mirblouk's office
state: Guilan
city: Rasht
country: Iran, Islamic Republic of
facility: Razi Hospital
state: Guilan
city: Mashhad
country: Iran, Islamic Republic of
facility: Dr. Aboulqasem Allahyari's office
state: Khorasan Razavi
city: Mashhad
country: Iran, Islamic Republic of
facility: Imam Reza Hospital
state: Khorasan Razavi
city: Mashhad
country: Iran, Islamic Republic of
facility: Qaem Hospital
state: Khorasan Razavi
city: Mashhad
country: Iran, Islamic Republic of
facility: Sanabad Hospital
state: Khorasan Razavi
city: Ahvaz
country: Iran, Islamic Republic of
facility: Arvand Hospital
state: Khozestan
city: Ahvaz
country: Iran, Islamic Republic of
facility: Baqaei Hospital
state: Khozestan
city: Ahvaz
country: Iran, Islamic Republic of
facility: Shafa Hospital
state: Khozestan
city: Isfahan
country: Iran, Islamic Republic of
facility: Milad Hospital
city: Isfahan
country: Iran, Islamic Republic of
facility: Saba Clinic
city: Isfahan
country: Iran, Islamic Republic of
facility: Seyed-Al-Shohada Hospital
city: Isfahan
country: Iran, Islamic Republic of
facility: Sheikh Mofid Clinic
city: Kermanshah
country: Iran, Islamic Republic of
facility: Dr. Mehrdad Payende's office
city: Kerman
country: Iran, Islamic Republic of
facility: Dr. Behjat Kalantari's office
city: Kerman
country: Iran, Islamic Republic of
facility: Javad-Al-Aemeh Clinic
city: Kerman
country: Iran, Islamic Republic of
facility: Shahid Bahonar Hospital
city: Shiraz
country: Iran, Islamic Republic of
facility: Amir Hospital
city: Shiraz
country: Iran, Islamic Republic of
facility: Namazi Hospital
city: Shiraz
country: Iran, Islamic Republic of
facility: Shahid Faghihi Hospital
city: Tabriz
country: Iran, Islamic Republic of
facility: Shams Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Baqiatallah Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: BuoAli Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Dr. Safa Najjar Najafi's office
city: Tehran
country: Iran, Islamic Republic of
facility: Ebn-Sina Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Firoozgar Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Imam Khomeini Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Iran-Mehr Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Jam Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Jihad University Clinic
city: Tehran
country: Iran, Islamic Republic of
facility: Masih Daneshvari Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Massoud Clinic
city: Tehran
country: Iran, Islamic Republic of
facility: Mehrad Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Naft Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Rasool Akram Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Resalat Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Sajjad Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Sina Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Taleghani Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Tehran Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Toos Hospital
city: Yazd
country: Iran, Islamic Republic of
facility: Dr.Mortazavizadeh's office
Study officials:
affiliation: Assistant Professor of Hematology and Oncology Research Center
name: Behrouz Najafi, MD
role: PRINCIPAL_INVESTIGATOR
References: