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

HER2-positive Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04957212
• Other study ID #: PER.CIN.BN.95.III
• Status: Completed
• Phase: Phase 3
• Start date: August 11, 2018
• Est. completion date: May 27, 2020

Study information

• Verified date: June 2021
• Source: Cinnagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: May 27, 2020
• Est. primary completion date: May 27, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-positive Breast Cancer

Intervention

Drug:
• Trastuzumab
An initial dose of 8 mg/kg, followed by 6 mg/kg every 3-weeks
• Pertuzumab
An initial dose of 840 mg, followed by 420 mg every 3-weeks
• Carboplatin
A dose of AUC6 (area under the plasma concentration-time curve) every 3-weeks
• Docetaxel
75 mg/m2 every 3-weeks

Locations

Country	Name	City	State
Iran, Islamic Republic of	Arvand Hospital	Ahvaz	Khozestan
Iran, Islamic Republic of	Baqaei Hospital	Ahvaz	Khozestan
Iran, Islamic Republic of	Shafa Hospital	Ahvaz	Khozestan
Iran, Islamic Republic of	Milad Hospital	Isfahan
Iran, Islamic Republic of	Saba Clinic	Isfahan
Iran, Islamic Republic of	Seyed-Al-Shohada Hospital	Isfahan
Iran, Islamic Republic of	Sheikh Mofid Clinic	Isfahan
Iran, Islamic Republic of	Dr. Behjat Kalantari's office	Kerman
Iran, Islamic Republic of	Javad-Al-Aemeh Clinic	Kerman
Iran, Islamic Republic of	Shahid Bahonar Hospital	Kerman
Iran, Islamic Republic of	Dr. Mehrdad Payende's office	Kermanshah
Iran, Islamic Republic of	Dr. Aboulqasem Allahyari's office	Mashhad	Khorasan Razavi
Iran, Islamic Republic of	Imam Reza Hospital	Mashhad	Khorasan Razavi
Iran, Islamic Republic of	Qaem Hospital	Mashhad	Khorasan Razavi
Iran, Islamic Republic of	Sanabad Hospital	Mashhad	Khorasan Razavi
Iran, Islamic Republic of	Besat Clinic	Rasht	Guilan
Iran, Islamic Republic of	Dr. Behrouz Najafi's office	Rasht	Guilan
Iran, Islamic Republic of	Dr. Mehdi Mirblouk's office	Rasht	Guilan
Iran, Islamic Republic of	Razi Hospital	Rasht	Guilan
Iran, Islamic Republic of	Amir Hospital	Shiraz
Iran, Islamic Republic of	Namazi Hospital	Shiraz
Iran, Islamic Republic of	Shahid Faghihi Hospital	Shiraz
Iran, Islamic Republic of	Shams Hospital	Tabriz
Iran, Islamic Republic of	Baqiatallah Hospital	Tehran
Iran, Islamic Republic of	BuoAli Hospital	Tehran
Iran, Islamic Republic of	Dr. Safa Najjar Najafi's office	Tehran
Iran, Islamic Republic of	Ebn-Sina Hospital	Tehran
Iran, Islamic Republic of	Firoozgar Hospital	Tehran
Iran, Islamic Republic of	Imam Khomeini Hospital	Tehran
Iran, Islamic Republic of	Iran-Mehr Hospital	Tehran
Iran, Islamic Republic of	Jam Hospital	Tehran
Iran, Islamic Republic of	Jihad University Clinic	Tehran
Iran, Islamic Republic of	Masih Daneshvari Hospital	Tehran
Iran, Islamic Republic of	Massoud Clinic	Tehran
Iran, Islamic Republic of	Mehrad Hospital	Tehran
Iran, Islamic Republic of	Naft Hospital	Tehran
Iran, Islamic Republic of	Rasool Akram Hospital	Tehran
Iran, Islamic Republic of	Resalat Hospital	Tehran
Iran, Islamic Republic of	Sajjad Hospital	Tehran
Iran, Islamic Republic of	Sina Hospital	Tehran
Iran, Islamic Republic of	Taleghani Hospital	Tehran
Iran, Islamic Republic of	Tehran Hospital	Tehran
Iran, Islamic Republic of	Toos Hospital	Tehran
Iran, Islamic Republic of	Dr.Mortazavizadeh's office	Yazd

Sponsors (1)

Lead Sponsor	Collaborator
Cinnagen

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	18-20 weeks after first intervention
Secondary	Total Pathological Complete Response (tpCR)	tpCR defined as no invasive tumor residues in the breast and lymph nodes (ypT0/is ypN0)	18-20 weeks after first intervention
Secondary	Objective response rate (ORR)	ORR defined as the proportion of patients who achieved a complete or partial response	18-20 weeks after first intervention
Secondary	Rate of breast-conserving surgery (BCS)	Rate of BCS for patients for whom mastectomy was planned before treatment (T2-3)	18-20 weeks after first intervention
Secondary	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.	Throughout the study duration (from first visit to week 18-20)
Secondary	Abnormal laboratory data	The abnormality in selected laboratory data was considered as adverse event and was reported.	Throughout the study duration (from first visit to week 18-20)
Secondary	Decline in LVEF of =10% points from baseline to <50%	LVEF decrease was measured by echocardiography.	every 6 week (from first visit to week 18-20)
Secondary	Incidence of symptomatic left ventricular systolic dysfunction (LVSD)	symptoms of LVSD were monitored by physician and reported as AEs.	Throughout the study duration (from first visit to week 18-20)
Secondary	Immunogenicity	antidrug antibody [ADA] assessment	Every 3 weeks (from first intervention to week 18)