CTRI/2025/09/094678 [Registered on: 12/09/2025] Trial Registered Prospectively
Last Modified On:
29/12/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A phase 3 clinical study conducted across multiple sites, an unpremeditated, unmasked trial, standard of care, side-by-side comparison study of Pyrotinib plus Capecitabine compared with Lapatinib plus Capecitabine in patients with HER2-positive advanced breast cancer.
Scientific Title of Study
A phase III, multicentre, randomized, open label, active controlled, parallel group, non-inferiority study of Pyrotinib plus Capecitabine compared with Lapatinib plus Capecitabine in patients with HER2-positive metastatic breast cancer
Trial Acronym
Nil
Secondary IDs if Any
Secondary ID
Identifier
DRL-IND-NDA14-PYR-CAP/2023, Version 2.0 dated 06 Mar 2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr M Rajalakshmi
Designation
Manager
Affiliation
Syngene International Limited
Address
Tower-1, Semicon Park, Electronic City (Phase II), Hosur Road, Bangalore, India
Bangalore KARNATAKA 560100 India
Phone
9980187480
Fax
Email
m.rajalakshmi@syngeneintl.com
Details of Contact Person Scientific Query
Name
Dr A C Gangaram
Designation
Clinical Development Expert
Affiliation
Dr Reddy’s Laboratories
Address
Integrated Product Development Organization, Innovation Plaza, Survey no.’s.: 42, 45, and 46, Bachupally village, Bachupally Mandal, Medchal-Malkajgiri district,
Telangana, Hyderabad,
Medchal TELANGANA 500 090 India
Phone
9740694650
Fax
Email
acgangaram@drreddys.com
Details of Contact Person Public Query
Name
Dr A C Gangaram
Designation
Clinical Development Expert
Affiliation
Dr Reddy’s Laboratories
Address
Integrated Product Development Organization, Innovation Plaza, Survey no.’s.: 42, 45, and 46, Bachupally village, Bachupally Mandal, Medchal-Malkajgiri district,
Telangana, Hyderabad,
Medchal TELANGANA 500 090 India
Phone
9740694650
Fax
Email
acgangaram@drreddys.com
Source of Monetary or Material Support
Dr. Reddy’s Laboratories Ltd.
Integrated Product Development Organization, Innovation plaza, Survey No: 42, 45 and 46, Bachupally village, Bachupally Mandal Medchal Malkajgiri District 500 090,
Telangana, India.
Primary Sponsor
Name
Syngene International Limited
Address
Translational and Clinical Research, Tower-I, Semicon Park,
Electronic City, Phase – II, Hosur Road, Bangalore – 560 100, India
Kiran Hospital Multi Super Speciality Hospital & Research Center
Kiran Hospital Multi Super Speciality Hospital and Research Center, Nr. Sumul Dairy, Surat-395004, Gujarat Surat GUJARAT
9428638448
drpriyalrsavaliya@gmail.com
Dr Praveena Voonna
Mahathma Gandhi Cancer Hospital & Research Institute
Mahathma Gandhi Cancer Hospital & Research Institute, 1/7, MVP Colony, Visakhapatnam-530017, Andra Pradesh Visakhapatnam ANDHRA PRADESH
9502885780
voonna@gmail.com
Dr Krishna Kumar Rathnam
Meenakshi Mission Hospital & Research Centre
Meenakshi Mission Hospital & Research Centre, Lake Area, Melur Road, Madurai-625107 Madurai TAMIL NADU
9380417299
kkrathnam@gmail.com
Dr P Krishna Chaitanya
MNJ Institute of Oncology and Regional Cancer Center
MNJ Institute of Oncology and Regional Cancer Center, Red Hills, Hyderabad, Telangana-500004 Hyderabad TELANGANA
8897199994
mnjiorccchaithanya@gmail.com
Dr Agarwala Vivek
Rabindranath Tagore International Institute of Cardiac Sciences
Rabindranath Tagore International Institute of Cardiac Sciences, Prmises No. 1489, (124), Mukundapur, E M Bypass, Kolkata- 700099 Kolkata WEST BENGAL
8879222875
drvivekagarwala@gmail.com
Dr Shriniwas Kulkarni
Sahayadri Super Speciality Hospital
Sahayadri Super Speciality Hospital, Sr. No. 163, Bhosale Nagar, Hadapsar,
411028 Pune MAHARASHTRA
9970279428
drshriniwaskulkarni@gmail.com
Dr Prabhat Bhargava Ghanshyam
Tata Memorial Hospital
Ernest Borges Road Parel Mumbai Maharashtra Mumbai MAHARASHTRA
7276174221
bhargava611@gmail.com
Dr Poladia Bhavesh Pradip
Thangam Hospital
Thangam Cancer Center and Research Institute, Associate Concern of Thangam Hospital, No. 54, Dr. Sankaran Road, Tamil nadu, India- 637001 Namakkal TAMIL NADU
9819151554
bhaveshpoladia@gmail.com
Dr Toka Vishal
TX Hospitals
TX Hospitals, Block I 8-2-679, Block II 8-2-680/A, Road No. 12, Banjara Hills, Hyderabad, Telangana- 500034 Hyderabad TELANGANA
1. Males and females aged equal to or more than 18 years.
2. Patients with histological or cytological confirmed HER2 positive advanced breast cancer who have been previously treated with more than or equal to 1 prior HER2 directed therapy for advanced disease and for whom the investigator has planned Lapatinib plus Capecitabine as the intended regimen.
Note, HER2 positive status will be assessed with 3 plus staining intensity by immune histochemistry or HER2 gene amplification by fluorescence in situ hybridisation indicating HER2 positivity. A HER2 positive breast cancer confirmed by the pathology department of the participating study centre.
3. At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1.
4. ECOG physical performance 0 to 1
5. Subjects willing to comply with protocol requirements
6. Willing to provide written informed consent
7. Lab parameters should meet the following requirements:
ANC, more than or equal to 1.5 x 109 per Liter, Platelet more than or equal to 90 x 109 per Liter, Hb more than or equal to 9.0 gm per dl, Total bilirubin more than or equal to 1.0 x upper limit of normal, ALT and AST more than or equal to 2 x ULN, patients with liver metastases, less than or equal to 5 x ULN, Creatinine less than or equal to 1 x ULN, creatinine clearance less than or equal to 50 mL per min, LVEF less than or equal to 50 percent.
8. Fridericia-corrected QT interval less than 450 msec for males and less than 470 msec for females
9. Female subjects of child-bearing potential should have negative serum pregnancy test at screening and agree to use adequate birth control during the entire study period.
a. For women who are not postmenopausal, postmenopausal defined as more than or equal to 12 months of Non therapy induced amenorrhea, or surgically sterile, absence of ovaries and or uterus agreement to remain abstinent or use single or combined non hormonal contraceptive methods that result in a failure rate of less than 1 percent per year during the treatment period and for at least 8 weeks after the last dose of study treatment
b. Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence e.g., calendar, ovulation, or post ovulation methods and withdrawal are not acceptable methods of contraception.
c. Examples of non hormonal contraceptive methods with a failure rate of less than 1 percent per year include tubal ligation, male sterilization, and certain non hormonal intrauterine devices. Alternatively, two methods, e.g., two barrier methods such as a condom and a cervical cap, may be combined to achieve a failure rate of less than 1percent per year. Barrier methods must always be supplemented with the use of a spermicide
d. For men, agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of less than 1 percent per year during the treatment period and for at least 1 week after the last dose of study treatment
e. Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence e.g., calendar, ovulation, or post ovulation methods and withdrawal are not acceptable methods of contraception
ExclusionCriteria
Details
1. History of hypersensitivity or allergy to any of the study drugs or its components
2. Received radiotherapy, chemotherapy, surgery, major surgery for breast cancer, or molecular targeted therapy within 4 weeks prior to randomization, received endocrine therapy within 7 days prior to randomization.
3. History of other malignant tumors in the past 5 years, other than cured cervical carcinoma in situ, basal or squamous cell carcinoma of skin
4. Presence of central nervous system metastases, definitive diagnosis of brain tumor by cranial CT or MRI scan
5. Presence of Dihydropyrimidine Dehydrogenase deficiency
6. Any antitumor treatment after informed consent and before randomization
7. Previous or current treatment with any tyrosine kinase inhibitor, including lapatinib, neratinib, and pyrotinib, targeting HER2
8. Previous capecitabine treatment for metastatic disease or in the neoadjuvant or adjuvant setting within 6 months before randomisation
9. History of exposure to the following cumulative doses of anthracyclines.
Doxorubicin or doxorubicin liposome more than 360 mg per meter square
Epirubicin more than 720 mg per meter square,
Mitoxantrone more than 120 mg per meter square
idarubicin more than 90 mg per meter square
10. Factors influencing the oral administration in affected patients e.g. dysphagia, chronic diarrhea, intestinal obstruction, etc.
11. Uncontrolled third space effusion, such as pleural fluid and ascites, by drainage or other clinical intervention
12. Known history of any immunodeficiency disease, acquired or congenital immunodeficiency disease, or history of organ transplantation
13. History or presence of interstitial lung disease and or pneumonitis
14. No radiologically confirmed disease progression during or after the most recent anti tumor treatment before enrollment, as assessed by the investigator
15. Subjects with significant cardiovascular history such as Congestive heart failure, myocardial infarction, angina pectoris, stroke or transient ischemic attack, arrhythmia, or any other within 6 months prior to randomisation
16. Subjects who used the concomitant drugs, enlisted in section 7.3 that interfere with liver P450 enzymes or Pgp within 5 half lives of the concomitant drugs prior to the pyrotinib administration
17. Subject having any medical condition or any significant laboratory finding, which in the opinion of the investigator, will interfere with the study results or increase the risk of adverse events.
18. Female subjects who are Pregnant or lactating
19. Subjects with history of drug or alcohol abuse
20. Receipt of any drug as part of a research study within 30 days prior to screening
21. Subjects with donation or transfusion of blood, plasma, or platelets within the past 3 months prior to randomisation
22. Known case of HIV, HBV or HCV
Method of Generating Random Sequence
Permuted block randomization, fixed
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To evaluate the efficacy of Pyrotinib plus Capecita-bine compared with Lapatinib plus Capecitabine in patients with HER2-positive metastatic breast cancer.
To evaluate the efficacy of Pyrotinib plus Capecita-bine compared with Lapatinib plus Capecitabine in patients with HER2-positive metastatic breast cancer.
Secondary Outcome
Outcome
TimePoints
To evaluate the safety and tolerability of Pyrotinib plus Capecitabine compared with Lapatinib plus Capecitabine in patients with HER2-positive meta-static breast cancer.
1. Objective Response Rate (defined as the proportion of patients with the best response of complete response [CR] or partial response [PR] per RE-CIST 1.1 at 12 months
2. Duration of Response, the time from the first complete or partial response to death or progression, whichever occurs first, at 12 months
3. Clinical Benefit Rate i.e., the proportion of patients with a best overall response of complete response, partial response, or stable disease for more or equal to 24 weeks, at 12 months
Exploratory Endpoint:
Proportion of patients with overall survival at 18 months.
Target Sample Size
Total Sample Size="136" Sample Size from India="136" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
25/09/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="9" Days="0"
Recruitment Status of Trial (Global)
Not Yet Recruiting
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
An
open label, multicenter, randomized, phase 3 study (PHOEBE trial) revealed that
Pyrotinib plus capecitabine significantly improved PFS (12.5 months vs 6.8
months, p<0.0001) when compared with lapatinib plus capecitabine in patients
with metastatic breast cancer. Furthermore, in phase 3 PHENIX study, Pyrotinib
plus capecitabine significantly prolonged PFS (11.1 months’ vs 4.1 months,
p<0.001) compared with capecitabine monotherapy in patients with HER2+
local-relapsed or metastatic breast cancer, who had received trastuzumab and
taxanes.
Thus,
in order to compare the efficacy and safety of Pyrotinib plus capecitabine
versus lapatinib plus capecitabine as treatment in subjects with HER2-positive
metastatic breast cancer, a phase III, randomized, open label, active
controlled, parallel-group, non-inferiority, multicenter study has been
proposed in Indian subjects.