CTRI/2020/02/023101 [Registered on: 04/02/2020] Trial Registered Prospectively
Last Modified On:
13/02/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A study of Goserelin 3.6 mg Injection in patients with Breast cancer.
Scientific Title of Study
A phase III, two arm, multicentric, randomized, open label, parallel, multiple dose pharmacodynamics study of Goserelin 3.6 mg Injection (Eurofarma Laboratorios S. A.) administered subcutaneously in comparison with the reference drug ZOLADEX® 3.6 mg Injection (AstraZeneca) administered subcutaneously in premenopausal patients with advanced Breast cancer.
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Prashant Modi
Designation
Senior General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of Project Management & Regulatory Affairs, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G.
Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202375
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr Naman Shah
Designation
General Manager
Affiliation
Lambda Therapeutic Research Ltd.
Address
Lambda House, Department of CTM Medical Services, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G. Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202389
Fax
07940202021
Email
namanshah@lambda-cro.com
Details of Contact Person Public Query
Name
Mr Prashant Modi
Designation
Senior General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of Project Management & Regulatory Affairs, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G.
Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202375
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Source of Monetary or Material Support
Eurofarma Laboratorios S.A
3465 Vereador Jose Diniz Ave
São Paulo – Brazil - 04603-000, Tel. No. 0551150908412,
Fax No. 0551150908742
Primary Sponsor
Name
Eurofarma Laboratorios SA
Address
3465 Vereador Jose Diniz Ave São Paulo – Brazil - 04603-000, Tel. No. 0551150908412, Fax No. 0551150908742
Department of clinical research, Room No.-32/2A, Erandwane-411004 Pune MAHARASHTRA
09823092932
sherwar@gmail.com
Dr Saroj Kumar Das Majmudar
All India Institute of Medical Sciences
Department of Radiotherapy,Room No .NA,AIIMS, Sijua, Patrapada, Po-Dumduma, Bhubhneshwar-751019 Khordha ORISSA
09438884096
sarojmajumdar@gmail.com
Dr K G Srinivas
Bharath Hospital & Institute of Oncology
Department of clinical research, Room No.-#438, Outer Ring Road-570017 Mysore KARNATAKA
09663121728
drsrinivas.kg@gmail.cm
Dr K Velavan
Erode Cancer Centre Private Ltd.
Department of clinical research, Room No : 1/393, Velavan Nagar, Perundurai Road, Thindal - 638 012.
Erode TAMIL NADU
09842334222
kvels@rediffmail.com
Dr Tushar patil
Global Hospital & Research Institute
Department of clinical research, Room No.577/2,Near Dattawadi Police Chowky, Off. Sinhgad Road, Dattawadi-411030 Pune MAHARASHTRA
09552522556
drtusharvpatil@gmail.com
Dr Pinaki Mahato
HCG Cancer Centre
Department of clinical research, Room No, NA,Sun Pharma Road, Opp. Satsang Party Plot-390012 Vadodara GUJARAT
09998974704
pinaki.mahato@hcghospitals.in
Dr Rajnish Vasant Nagarkar
HCG Manavata Cancer Centre
Department of clinical research, Room No.NA,Behind Shivr
Mumbai Naka- 422002 Nashik MAHARASHTRA
09823061929
drraj@manvatacancercentre.com
Dr Niraj Bhatt
Isha Hospital
Department of clinical research, Room No. NA, Sarabhai Campus, Sarabhai Main Road Behind, Atlantis Ln, Vadodara" Gujarat 390007 Vadodara GUJARAT
9925581480
research.wecare@gmail.com
Dr Niraj Bhatt
Kailash Cancer Hospital and Research Centre
Department of clinical research, Room No.NA,Muni Seva Ashram, Goraj, Waghodia-391760 Vadodara GUJARAT
09925581480
niraj.bhatt@greenashram.org
Dr Rohan Bhise
KLES Dr. Prabhakar Kore Hospital & Medical Research Centre
Department of clinical research, Room No: NA,Nehrunagar, Belagavi-590010, India
Belgaum KARNATAKA
07975558921
rohanbhise30@gmail.com
Dr Praveena Voonna
Mahatma Gandhi Cancer Hospital & Research Institute
Department of clinical research, Room No. NA, Plot No. 1, Sector:7, MVP Colony-530017 Visakhapatnam ANDHRA PRADESH
9502885780
praveena.voonna@gmail.com
Dr Sandhya Rani Nippani
MNJ Institute of Oncology & Regional Cancer Centre
Department of Clinical Research, Room no. NA, Red Hills, Hyderabad-500004, Telangana, India Hyderabad TELANGANA
9849352598
sandhyanippani@gmail.com
Dr Kshitij Joshi
Mumbai Oncocare Centre
Department of clinical research, Room No. NA,2nd Floor, Majithia
Apartments, Gods Gift Premises co-op Soc Ltd, S V Road, Vile Parle ( W)- 400 056. Mumbai MAHARASHTRA
Department of clinical research, Room No, NA,"Plot No.8, Motkari Nagar, Behind Tupsakhare Lawns, Tidke Colony, Mumbai Naka-422002; India
Nashik MAHARASHTRA
09766126162
drbtnemade@yahoo.co.in
Dr Rakesh Neve
P.D.E.As, Ayurved Rugnalaya and Sterling Multispeciality Hospital
Department of clinical research, Room No.NA,Sector 27, Near Bhel Chawk, Pradhikaran,Nigdi-411044
Pune MAHARASHTRA
09881143140
rakesh.neve23@gmail.com
Dr Minish Jain
Ruby Hall Clinic
Department of clinical research, Room No-40, Sassoon Road-411001 Pune MAHARASHTRA
09823133390
minishjain009@gmail.com
Dr Rajendra Singh Arora
Sujan Surgical Cancer Hospital & Amravati Cancer Foundation
Department of clinical research, Room No.52/B Shankar Nagar, Main Road, -444606, Amravati MAHARASHTRA
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Goserelin acetate 3.6 mg Injection of Eurofarma Laboratorios S.A
Dose: 3.6 mg; Frequency: every 28 days; Mode of Administration: Subcutaneously ;Duration of treatment: day 1, 29 and 57.
Comparator Agent
ZOLADEX® 3.6mg Injection of AstraZeneca UK Limited
Dose: 3.6 mg; Frequency: every 28 days; Mode of Administration: Subcutaneously ;Duration of treatment: day 1, 29 and 57.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
50.00 Year(s)
Gender
Female
Details
1. Pre-menopausal female patients of 18 to 50 years of age (both inclusive).
2. BMI 18.5 to 30 kg/m2 (both inclusive).
3. Patient with a confirmed diagnosis of advanced breast cancer (TNM stage III or
stage IV or recurrent metastatic disease) who are scheduled to start goserelin
therapy as per Investigator discretion.
4. Hormone sensitivity (ER positive) of primary or secondary tumour tissue
5. Patients with baseline estradiol levels >30 pg/mL
6. Patients must be able to understand the investigational nature of this study and to give written informed consent prior to the participation in the trial.
7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
8. Patients with life expectancy of at least 3 months as judged by the Investigator.
9. Patient should have recovered from any toxic effects of previous
chemotherapy as judged by the Investigator.
10. Patient should be able to comply with study requirement in the opinion of Investigator.
11. Non-smoker defined as non-smoker for at least 6 months (i.e. subject has not smoked or used any tobacco products for the 6 months prior to the screening visit).
12. Patients must not have taken any anti-androgens, estrogen, antiestrogen, selective estrogen receptor modulators, aromatase inhibitors or hormonal forms of contraception within past one month of screening. Patient may have had recent use of oral contraceptive pills but these must be discontinued 30 days prior to dosing.
13. Adequate hematologic status, renal and liver function.
14. Women of childbearing potential must not be pregnant or breastfeeding (as documented by a negative serum pregnancy test at screening
and negative urine pregnancy test at baseline).
15. Women of childbearing potential or her partner must use an acceptable and effective non-hormonal method of avoiding pregnancy,
starting at least four weeks before the study drug administration and up to 12 weeks after the after the last dose of study drug administration. Cessation of birth control after this point should be discussed with the responsible physician. For this study, acceptable and effective methods of contraception include:
a) Tubal sterilization (tubal ligation performed more than one month before Study Day 1; transcervical tubal occlusion procedure performed more than six months before Study Day 1)
b) Barrier method (cervical cap, diaphragm, contraceptive sponge, vaginal spermicide, female condom, or male condom)
c) Two barrier methods used together (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide plus a male or female condom)
d) Absolute sexual abstinence (no sexual intercourse or genital contact with a
male partner). If the patient becomes sexually active during the study, then she is required to use a double barrier method of contraception.
ExclusionCriteria
Details
1. Patients who are not able to provide written informed consent.
2. Patients who are menopausal.
3. Patients who are scheduled to receive any chemotherapy/radiotherapy in addition to goserelin.
4. Patients who are already on GnRH receptor agonist or antagonist therapy.
5. Patients who have previously failed on GnRH receptor agonist or antagonist therapy.
6. Presence of life-threatening metastatic visceral disease, defined as extensive hepatic involvement, or any degree (proven or suspected) of brain or leptomeningeal involvement (past or present) or symptomatic pulmonary lymphangitic spread. Patients with discrete pulmonary parenchymal metastases
are eligible, provided their respiratory function is not compromised as a result of the disease.
7. Patients who are intended to be started on any medication apart from study drug that can have impact on any of the study endpoints.
8. Patients who are pregnant or breastfeeding.
9. Concurrent malignancy or history of malignancy (apart from disease condition
under study) within last 5 years before screening except curatively treated carcinoma in situ of the uterine cervix or basal cell carcinoma of the skin
10. Patients with a clinically significant medical condition other than advanced breast cancer including but not limited to renal, hepatic, gastrointestinal, endocrine, cardiovascular, neurological or psychiatric disease, alcohol or substance abuse, or any other condition that may affect the patient health or the outcome of the trial as judged by the investigator.
11. Presence of clinically significant physical exam, laboratory, medical history, ECG/echocardiogram findings that in the opinion of the Investigator may interfere with trial conduct, patient safety, or interpretation of results.
12. Patients with a known hypersensitivity to GnRH, GnRH-agonist analogues or any of the components in IMP.
13. Patients receiving anticoagulation medications.
14. Patients with uncontrolled diabetes mellitus (HbA1c > 8 % as per ADA) at randomization (those who have controlled blood sugar (fasting) will be eligible for randomization)
15. Patients with confirmed signs or symptoms related to cerebral metastasis or radiographically confirmed brain metastasis.
16. Uncontrolled hypertension (systolic blood pressure [BP] >140 or diastolic BP >90mm Hg) or uncontrolled cardiac arrhythmias. (Patients with hypertension controlled by antihypertensive therapies are eligible).
17. Patients with a QTc>450ms on the ECG at screening.
18. History of clinically significant cardiovascular disorder
19. Use of any recreational drugs (cocaine, amphetamines, barbiturates, benzodiazepines, cannabinoids and morphine) or history of drug or alcohol abuse within the past 1 year, as judged by the Investigator, or a positive result on the urine drug/alcohol screen which is not consistent with current medical treatment.
20. Concomitant use of medicinal products known to prolong the QT interval or
medicinal products able to induce Torsade de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin,
antipsychotics.
21. A positive hepatitis screen including hepatitis B surface antigen or HCV antibodies.
22. Patients who test positive for HIV and/or syphilis.
23. The receipt of an investigational product, or participation in a drug research study within a period of 30 days prior screening or 5 half-lives within the last dose of investigational product, whichever is longer. Current use of any drugs that are known to interfere with goserelin metabolism or to cause a drug-drug interaction.
24. Donation / loss of blood/plasma or blood product (without replenishment) (1 unit or 350 mL) within 180 days prior to receiving the first dose of study medicine.
25. Patients with a mental incapacity, unwillingness, or language barrier that
precludes the ability to understand or cooperate with study procedures.
26. Presence of clinically significant findings on the physical exam, laboratory testing, medical history, ECG that in the opinion of the Investigator may interfere with trial conduct, patient safety, or interpretation of results.
27. Any contraindications for goserelin administration.
28. Females of reproductive potential unwilling to use acceptable contraception (as defined in the protocol) starting at least four weeks before the study drug administration and up to 12 weeks after the after the last dose of study drug administration.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Evaluation and comparision of the pharmacodynamics of test product against
reference product and establish non-inferiority.
For pharmacodynamics
Serum Estradiol:
Day 1, Day 2, Day 8, Day15, Day 22, Day 29, Day-36,
Day 43, Day 50, Day 57,
Day 64, Day 7), Day 78 and Day 85
Serum LH:
Day 1, Day 2, Day15, Day 29, Day 43, Day 57, Day 71 and Day 85
Serum FSH:
Day 1, Day 29, Day 57 and Day 85
Secondary Outcome
Outcome
TimePoints
Evaluation of the pharmacokinetic and safety of the test product as compared to reference product.
For pharmacokinetic
Pre-dose, Day 1, Day 2, Day 3, Day 6, Day 9, Day 13, Day 14, Day 15, Day 16, Day 17, Day 19, Day 21, Day 23, Day 25, Day 27 and Day 29
Target Sample Size
Total Sample Size="68" Sample Size from India="58" 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)
16/03/2020
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
01/04/2020
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="5" Days="0"
Recruitment Status of Trial (Global)
Not Yet Recruiting
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
None Yet
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
The current study is being conducted to evaluate the pharmacodynamics effect of test product (injection goserelin 3.6mg implant) against that of reference product and establish non-inferiority of test product as compared to reference product. Goserelin acetate is a synthetic analogue of gonadotropin-releasing hormone (GnRH). When given acutely, it transiently increases the plasma levels of luteinising hormone (LH) and follicle-stimulating hormone (FSH). This is a phase III, two arm, multi centric, randomized, open label, parallel, multiple dose pharmacodynamic study in premenopausal patients with advanced breast cancer This study is designed to establish pharmacodynamic comparability between the two products that can be maintained for the rest of the active treatment phase (once it has been achieved) rather than establishing pharmacokinetic comparability. 68 patients patients will be enrolled into the study. Attempt will be made to enrol equal number of patients in each treatment arm. Total duration of the study will be around 99 days (including 14 days of screening). The study will commence only after a written approval is obtained from the Institutional Ethics Committee and applicable regulatory authorities.