CTRI/2020/02/023211 [Registered on: 10/02/2020] Trial Registered Prospectively
Last Modified On:
26/03/2025
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 10.8 mg Injection in comparison with the drug ZOLADEX® 10.8 mg Injection in patients with prostate cancer.
Scientific Title of Study
A phase III, two arm, multi centric, randomised, open label, parallel study to compare pharmacodynamics of
Goserelin 10.8 mg Injection (Eurofarma Laboratórios S.A) administered subcutaneously with the reference
drug ZOLADEX® 10.8 mg Injection (AstraZeneca) in patients with advanced prostate 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 Laboratrios SA
Address
3465 Vereador Jose Diniz Ave São Paulo – Brazil - 04603-000, Tel.
No. 0551150908412, Fax No. 0551150908742
Nirmal Hospital Ethics committee, Dr. Kapil Thakkar
Approved
Sterling Hospital Institutional Ethics Committee, Dr. Rakesh Neve
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C61||Malignant neoplasm of prostate,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Goserelin acetate 10.8 mg Injection of Eurofarma Laboratorios S.A
Dose: 10.8 mg, Subcutaneously at every 3 months
Comparator Agent
ZOLADEX® 10.8mg Injection of AstraZeneca UK Limited
Dose: 10.8 mg, Subcutaneously at every 3 months
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Male
Details
1. Male patient with age of 18 to 75 years (Both inclusive)
2. Body mass index (BMI) between 18.5 and 30 kg/m². (Both inclusive)
3. Patient with a confirmed advanced prostatic adenocarcinoma. (TNM stage III or
IV or recurrent metastatic disease) who are scheduled to start Goserelin therapy as
per Investigator discretion.
Note: Stage III (T1–T2, N0, M0, PSA level is 20 or more, Grade Group 1–4 or
T3–
T4, N0, M0, any PSA, Grade Group 1–4 or any T, N0, M0, any PSA, Grade
Group 5). Stage IV (any T, N1, M0, any PSA, any Grade Group or any T, N0, M1,
any PSA, any Grade Group)
4. Serum testosterone level >2.5 ng/mL for age of 20 to 49 (both inclusive) and >1.9
ng/mL for age ≥ 50 at screening. (Screening sample for Serum testosterone level
should be taken before 10:00 am in the morning).
5. Patient must be able to give informed consent for participation in the trial.
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
7. Adequate bone marrow function, renal function, liver function.
8. Patient should have recovered from any toxic effects of previous chemotherapy as
judged by the Investigator.
9. Patients with life expectancy of at least 1 year as judged by the Investigator.
10. Patient or his partner willing to use an effective method as mentioned below of
contraception during the study:
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)
Absolute sexual abstinence (no sexual intercourse or genital contact with a female
partner). If the patient becomes sexually active during the study, then he is
required to use a double barrier method of contraception.
ExclusionCriteria
Details
1. Evidence of severe urinary tract obstruction with anticipated urinary retention, in
the opinion of the Investigator, taking into account medical history, clinical
observations and symptoms.
2. Patients who are scheduled to receive any chemotherapy/radiotherapy in addition
to goserelin.
3. Patients who are already on GnRH receptor agonist or antagonist therapy directed
for prostate cancer.
4. Patients who have previously failed on GnRH receptor agonist or antagonist
therapy for prostate cancer.
5. 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
lymhangitic spread. Patients with discrete pulmonary parenchymal metastases are
eligible, provided their respiratory function is not compromised as a result of
disease.
6. Patients who are intended to be started on any medication apart from study drug
that can have impact on any of the study endpoints.
7. Patients with spinal cord compression (in the opinion of the Investigator), taking
into account medical history, clinical observations and symptoms.
8. Excruciating, severe bone pain which is due to extensive metastatic osseous
deposits.
9. Patient has "currently active" second malignancy, other than non-melanoma skin
cancer. Patients are not considered to have a "currently active" malignancy if they
have completed therapy >5 years previously and have no known evidence of
residual or recurrent disease.
10. Patients with confirmed signs or symptoms related to cerebral metastasis or
radiographically confirmed brain metastasis.
11. Patients with a clinically significant medical condition other than advanced
prostate 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’s health or the
outcome of the trial as judged by the investigator.
12. Patients with a known hypersensitivity to GnRH, GnRH-agonist analogues or any
of the components in IMP.
13. History of orchiectomy, adrenalectomy or hypophysectomy.
14. Patients receiving anticoagulation medications.
15. Patients with uncontrolled diabetes mellitus (HbA1c > 8 % as per ADA) at
randomization (those who have controlled blood sugar (fasting) will be eligible
for randomization)
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.
Note: Any clinically significant findings should be discussed with the Medical
Monitor
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.
Pre-dose and Day 1, Day 2, Day 8, Day 15, Day 22, Day 29, Day 43, day 57, day 71, day 85 day 86, day 89, day 99, day 113, day 127, day 141, day 155 and day 169 hours post dose
Secondary Outcome
Outcome
TimePoints
Evaluation of the pharmacokinetic and safety of
the test product as compared to reference
product.
For pharmacokinetic
Pre-dose and at
Day 1, Day 2, Day 3,
Day 6, Day 9, Day 13, Day 17, Day 22, Day 29, Day 36, Day 43, Day 50, Day 60, Day 71 and Day 85 hours post-dose
Target Sample Size
Total Sample Size="94" Sample Size from India="84" 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)
01/05/2020
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="2" 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 10.8mg 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). Peak levels of LH and FSH usually occur 2 to 3 days after administration of a subcutaneous slow release depot formulation [1]. During continued administration of goserelin, the pituitary gland becomes refractory to further stimulation and serum levels of LH and FSH decline, leading to receptor desensitisation and/or down-regulation of the hypothalamic-pituitary gonadal axis. After about 2 weeks the LH and FSH serum levels reach pretreatment
values or lower. After this transient increase, the LH and follicle-stimulating hormone (FSH) production is down-regulated and testosterone production is inhibited. The decline in testosterone levels is similar to those observed after castration. Goserelin 10.8 mg Implant is a hybrid medicinal product. Bioavailability would be clinically not relevant as efficacy of GnRH analogues is independent of the pharmacokinetic profile as long as blood levels exceed a threshold level necessary to desensitise/downregulate pituitary receptors. There is no correlation between GnRH blood levels and the clinically meaningful suppression of testosterone below castration level. Therefore, the 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.