CTRI/2021/12/038914 [Registered on: 24/12/2021] Trial Registered Prospectively
Last Modified On:
28/07/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Crossover Trial
Public Title of Study
A Randomized, Open-Label, Multi center, Two Treatment, Two Period, Two Sequence, Single Dose, Crossover Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection 2mg/mL (50 mg/m dose)
Scientific Title of Study
A Randomized, Open-Label, Multicenter, Two Treatment, Two Period, Two Sequence, Single Dose, Crossover Bioequivalence Study Of Doxorubicin Hydrochloride Liposome Injection 2mg/mL (50 mg/m2 dose) Of Alembic Pharmaceuticals Limited, India And PrTaro-DOXOrubicin Liposomal 2mg/mL (Pegylated Liposomal Doxorubicin Hydrochloride for Injection) (50 mg/m2 dose) Of Taro Pharmaceuticals Inc, 130 East Drive, Brampton, Ontario, Canada, L6T 1C1, Administered in Patient With Advanced Ovarian Cancer Under Standard diet (non-high-fat) Conditions.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
G7SYN/P-002/2021, VERSION NO-01,Dated 04-06-2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Ajay Alexander
Designation
Medical Monitor
Affiliation
G7 Synergon Private Limited
Address
No 537 9th Cross 5th main Tata Nagar Sahakaranagar Post Bangalore Karnataka India
Bangalore KARNATAKA 560092 India
Phone
9916252529
Fax
Email
ajay.alexander@g7synergon.in
Details of Contact Person Scientific Query
Name
Dr D Sathish Kumar
Designation
Managing Director
Affiliation
G7 Synergon Private Limited
Address
No 537 9th Cross 5th main Tata Nagar Sahakaranagar Post Bangalore Karnataka India
Bangalore KARNATAKA 560092 India
Phone
9677014651
Fax
Email
sathishkumar@g7synergon.in
Details of Contact Person Public Query
Name
Dr D Sathish Kumar
Designation
Managing Director
Affiliation
G7 Synergon Private Limited
Address
No 537 9th Cross 5th main Tata Nagar Sahakaranagar Post Bangalore Karnataka India
KARNATAKA 560092 India
Phone
9677014651
Fax
Email
sathishkumar@g7synergon.in
Source of Monetary or Material Support
Alembic Pharmaceuticals
Primary Sponsor
Name
Alembic Pharmaceuticals Limited
Address
Alembic Pharmaceuticals Limited, Alembic Road, Vadodara - 390 003,Gujarat, India.
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 6
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Rajnish Nagarkar
HCG Manavata Cancer Centre
Behind Shivang Auto, Mumbai naka, Nashik, 422002, Maharashtra, India Nashik Nashik – 422002, Maharashtra, India Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Dhamne Nilesh Ashok
Kolhapur Cancer Centre Private Limited
R S 238, opposite Mayur petrol Pump, Gokul Shirgaon, Kolhapur-416234, Maharashtra, India Kolhapur MAHARASHTRA
7738245698
dr.nilesh.gmc@gmail.com
Dr Sharad Desai
Mahatma Gandhi Cancer Hospital
Near Gulabrao Patil Homeopathic Medical College, Shaskiya Dudh Diary Road, Shivajinagar, Miraj-416410, Maharashtra, India Sangli MAHARASHTRA
9850537099
drsharaddesai@gmail.com
Dr Balaji Shewalkar
Marathwada Regional Cancer Centre and Research Centre
Near Jama Masjid, Kil-e-Ark, Aurangabad-431001, Maharashtra, India Aurangabad MAHARASHTRA
9850632639
bshewalkar.pi@gmail.com
Dr Minish Jain
Nobel Hospital Private Limited
153, Magarpatta city road, Hadapsar
Pune- 411013, Maharashtra, India.
Pune MAHARASHTRA
9823133390
minishjain009@gmail.com
Dr Kane Shriram Bhagwan
Rashtra Sant Tukdoji Cancer Hospital and Research Centre
Rashtra Sant Tukdoji Cancer Hospital and Research Centre, Tukdoji Putla Square, Nagpur-440024, Maharashtra, India. Nagpur MAHARASHTRA
The prepared investigational product will be administered to the patient on day 1 (Period I) and day 29 (Period II) at least 2 hours after completion of breakfast i.e., the first day of the chemotherapy cycles.
Intervention
Test Product: Doxorubicin Hydrochloride Liposome Injection 2mg/mL Dose: 50 mg/m2
Manufactured by: Alembic Pharmaceuticals Limited, India.
The prepared investigational product will be administered to the patient on day 1 (Period I) and day 29 (Period II) at least 2 hours after completion of breakfast i.e., the first day of the chemotherapy cycles.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Female
Details
1. Willing and able to provide written informed consent.
2. Female patient between 18 and 65 years of age, both inclusive and having Body Mass Index (BMI) ≥ 17.00 kg/m2.
3. Documented diagnosis (histological confirmation) of ovarian cancer.
4. Patient with documented progressive or recurrent disease after treatment with platinum-based chemotherapy.
5. The patient is eligible and clinically indicated to receive the recommended minimum 2 cycles of Liposomal Doxorubicin HCl, without exceeding a lifetime cumulative dosage of 450 mg/m2. (Prior use of conventional or liposomal doxorubicin formulations, in addition to the use of other anthracyclines or anthracenediones should be included in calculations of total lifetime cumulative dose)
6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
7. The life expectancy of > 180 days.
8. No toxic effects of previous chemotherapy as judged by the Investigator.
9. Patient whose organ and immune system functions are adequate as indicated by the following laboratory values or considered by the Investigator/sub-Investigator to be of no clinical significance.
Hematologic
Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
Platelets ≥ 100 X 109/L
Hemoglobin ≥ 9.0 g/dL
Hepatic
Total bilirubin ≤ 1.3 mg/dL
(≤2 mg/dL for liver metastasis)
Alanine aminotransferase (ALT) ≤ 2.5 X ULN
(≤ 4 × ULN for liver metastasis)
Aspartate aminotransferase (AST) ≤ 2.5 X ULN
(≤ 4 × ULN for liver metastasis)
Alkaline phosphatase ≤ 2.5 X ULN
(≤ 5 × ULN for bone metastasis and ≤4×ULN for liver metastasis)
Renal
Serum creatinine < 1.5 x upper limit of normal (ULN)
Creatinine clearance ≥ 30 mL/min
10. Patient with cardiac ejection fraction ≥ 50% as measured by an echocardiogram (ECHO).
11. Patient must have clinically acceptable results for all the screening parameters and investigations.
12. Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of minor surgery; at least 4 weeks must have elapsed from the time of major surgery.
13. Willing to abstain from consuming grapefruit, citrus fruits, and its products 72 hours before randomization and throughout the study period
14. Willing to abstain from consuming any xanthine containing items (i.e., tea, coffee, cola drinks, or chocolate/coca, etc.) for 48 hours before randomization and throughout the study period
15. Availability of patient for the entire study duration and willingness to adhere to protocol requirements as evidenced by written informed consent.
16. No history of addiction to any recreational drug or drug dependence or alcohol addiction.
17. Female patient
a) of childbearing potential practicing an acceptable method of birth control such as sexual abstinence, (including oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of a condom with spermicide by a sexual partner or sterile [at least 6 months before Investigational Product administration] sexual partner) for at least 4 weeks before study drug administration, for the duration of the study and at least six months following discontinuation of doxorubicin therapy with a negative serum pregnancy test at screening and negative urine pregnancy test at Day 0. OR
b) Postmenopausal for at least the past 12 months. OR
c) Surgically sterile at least 6 months before Investigational Product administration (bilateral tubal ligation/hysterectomy has been performed on the patient).
ExclusionCriteria
Details
1. Pregnant and lactating female.
2. Patient with a history of known hypersensitivity or contraindication to conventional or liposomal formulations of doxorubicin, anthracycline therapy, or to any of their components.
3. Received liposomal doxorubicin HCl in the past and had a required dose reduction to below 50mg/m2, or whose disease has progressed or recurred after treatment with liposomal doxorubicin.
4. Patient whose total cumulative dose of doxorubicin HCl approaches 450 mg/m2.
5. Patient with brain metastases.
6. Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI criteria.
7. Patient with significantly impaired hepatic function.
8. Patient with clinically significant cardiac, liver or kidney disease.
9. Patient with history or presence of uncontrolled diabetes mellitus.
10. Patient having active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii, or other microorganism if under treatment with myelotoxic drugs.
11. Patient with impaired cardiac function including any of the following condition within past 6 months (To be judged based on the discretion of Investigator):
• Unstable angina or Myocardial infarction
• Significant ECG abnormalities
• Coronary artery bypass graft surgery
• Symptomatic peripheral vascular disease
• NYHA class II-IV heart failure
• Severe uncontrolled ventricular arrhythmias
12. Received any prior mediastinal irradiation (as cardiac toxicity may occur at cumulative doses lower than 400 mg/m2).
13. Patients who have taken any potent CYP3A4 inhibitors/inducers during the study and within ≤ 30 days before the day of first dosing including but not limited to: inhibitors - Ketoconazole, Itraconazole, Troleandomycin, Clarithromycin, Erythromycin, Ritonavir, Indinavir, Nelfinavir, Saquinavir, Amprenavir, Nefazodone, Fluvoxamine, Diltiazem, Verapamil, Mibefradil, Cimetidine, Cyclosporine; inducers - such as phenytoin, carbamazepine, phenobarbital, etc.
14. Patient with the use of Paclitaxel, Progesterone, Verapamil, Cyclosporine, Dexrazoxane, Cytarabine, Streptozocin as concurrent therapy.
15. Abnormal baseline findings are considered by the investigator to indicate conditions that might affect study endpoints.
16. Patients who have taken vaccination for COVID within 14 days before the day of first dosing.
17. Smoking (≥ 10 cigarettes/day) or consumption of tobacco products (≥ 4 chews/day)
18. Alcohol dependence, alcohol abuse, or drug abuse or addiction to any recreational drug within the past year.
19. Any other significant medical comorbidities or intercurrent illnesses or infections may have an impact on patient safety and do not permit the dosing of Doxorubicin HCl as determined by the Investigator.
20. Clinically assessed as having inadequate venous access for PK sampling.
21. Patient deemed uncooperative or non-compliant.
22. Patient who has shown positive results in urine alcohol test and/or urine drug screening test.
23. Significant abnormal 12 lead ECG, X-ray, and 2D-Echocardiography finding.
24. A positive result of HIV, HCV, RPR, and HBsAg.
25. Participation in another clinical trial within the preceding 90 days of study starts.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Cmax, AUC
Measured at 0.00 (prior to infusion), 0.250, 0.500, 0.750, 1.000, 1.250, 1.500, 2.000, 3.000, 4.000, 6.000, 8.000, 12.000, 16.000, 24.000, 36.000, 48.000, 72.000, 120.00, 168.00, 216.00, 264.00, 312.00 and 360.00 hours in two consecutive cycles (28 days washout period)
Secondary Outcome
Outcome
TimePoints
The secondary objective of this study is to evaluate the safety and tolerability of the patients exposed to the Doxorubicin Hydrochloride Liposome Injection administered in ovarian cancer patients whose disease has progressed or recurred after platinum-based chemotherapy and who are already receiving or scheduled to start therapy on doxorubicin hydrochloride (liposomal) under standard diet (non-high-fat) conditions.
At the end of the study when all 18 patients have completed the study
Target Sample Size
Total Sample Size="18" Sample Size from India="18" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a randomized, multi-centre, open-label, two treatment, two-period, single-dose, crossover, bioequivalence study of Doxorubicin Hydrochloride Liposome Injection 2mg/mL (50 mg/m2 dose) of Alembic Pharmaceuticals Limited, India and PrTaro-DOXOrubicin Liposomal 2mg/mL (Pegylated Liposomal Doxorubicin Hydrochloride) (50 mg/m2 dose for Injection) of Taro Pharmaceuticals Inc, 130 East Drive, Brampton, Ontario, Canada, L6T 1C1 in a patient with advanced ovarian cancer under standard diet (non-high-fat) conditions. Enough number of eligible consenting ovarian cancer patients whose disease has progressed or recurred after platinum-based chemotherapy and who are already receiving or scheduled to start therapy on doxorubicin hydrochloride (liposomal) shall be recruited to complete the study with at least eighteen (18) evaluable patients. All the subjects will be on overnight fasting of at least 10 hours before breakfast. All patients will be provided with a standard (non-high-fat) breakfast during the study and the treatment will be initiated at least 2 hours after completion of breakfast.
A gap of 28 days will be maintained between 2 periods of the study as per the dosing recommendation of the product.