Bioequivalence study of Doxorubicin HCL Liposome Inj 20mg/10mL(Dose:50mg/m2) of Emcure PharmaLtd.,India, compared to that of Doxorubicin HCL Liposome Inj for IV Infusion20mg/10mL(Dose:50mg/m2) OFJANSSEN-CILAG INTERNATIONAL NV BELGIUM, in female patients with ovarian cancer in fasting condition

Phase 1

Completed

• Conditions: ADVANCED OVARIAN CANCER WHO HAVE FAILED A FIRST-LINEPLATINUM-BASED CHEMOTHERAPY REGIMEN AND WHO ARE ALREADYRECEIVING OR SCHEDULED TO START DOXORUBICINHYDROCHLORIDE LIPOSOME INJECTION

• Registration Number: CTRI/2018/06/014575
• Lead Sponsor: Emcure Pharmaceuticals Ltd

Brief Summary

A Multicenter, Open label, Randomized, Balanced, Two-treatment, Two-period,Two-sequence, Single dose, Two-way crossover, Bioequivalence study in female

patients with advanced ovarian cancer who have failed a first-line platinum-based

chemotherapy regimen and who are already receiving or scheduled to start

therapy with the Doxorubicin Hydrochloride Liposome Injection under fasting

condition.



Primary Objective:

To assess the bioequivalence of Doxorubicin Hydrochloride Liposome

concentrate for solution for infusion 2 mg/mL at a dose of 50mg/m2 of Emcure

Pharmaceuticals Ltd., India, compared to that of Caelyx 2 mg/mL concentrate for

solution for infusion (each mL containing 2 mg doxorubicin hydrochloride in a

pegylated liposomal formulation) at a dose of 50mg/m2 of Janssen-Cilag

International NV, Belgium., in female patients with advanced ovarian cancer who

have failed a first-line platinum-based chemotherapy regimen and who are already

receiving or scheduled to start therapy with the doxorubicin hydrochloride liposome

injection under fasting condition.

Secondary objective:

To monitor the safety and tolerability of a single dose administered in female

patients with advanced ovarian cancer who have failed a first-line platinum-based

chemotherapy regimen and who are already receiving or scheduled to start therapy

with the doxorubicin hydrochloride liposome injection under fasting conditions.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-06-28
• Last Update Posted: 2019-06-05
• Study Completion: 2019-07-01

Recruitment & Eligibility

• Status: Completed
• Sex: Female
• Target Recruitment: 56

Inclusion Criteria

• Female patients, 18 to 75 years of age (both inclusive) and having a Body Mass Index (BMI) at least 17 kg/m2.
• Have histologically or cytologically confirmed advanced ovarian cancer 3.
• Patients with advanced ovarian cancer who have failed a first-line platinum-based chemotherapy regime and who are already receiving or scheduled to start Doxorubicin Hydrochloride liposomal injection 50 mg/m2 dose as monotherapy as per Investigator judgment.
• Patients with life expectancy for at least 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (The woman should be ambulatory, capable of all self-care, up for more than 50% of waking hours.
• She may or may not be able to carry out any work activities).
• Patients should preferably be on monotherapy.
• However, cancer patients receiving concomitant medications are allowed to participate provided: The concomitant medication and their dosing regimen are expected to be same for both the study periods.
• The concomitant medications do not interfere with the study drug (If concomitant medication is required during the study period, the patients will be treated accordingly, and a decision to continue or discontinue the patients will be made by the investigator).
• Availability of patient for the entire study period and willingness to adhere to Protocol requirements as evidenced by the written ICF duly signed by the patient.
• Either the female is of non-child bearing potential (females having documented history of surgical sterilization or are postmenopausal (12 months of amenorrhea after the last menstrual period) or if the female is of child bearing potential, then she is eligible if: Patient has used an effective method of contraception or abstinence from at least 4 weeks prior to study drug administration.
• Effective method includes: 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) Intrauterine Device (IUD) Progestin Implant (i.e. Implanon or its equivalent) Progestin injection or progestin oral contraceptive pill + one barrier method (cervical cap, diaphragm, contraceptive sponge or vaginal spermicide + a male or female condom) Two barrier methods used together (cervical cap, diaphragm, contraceptive sponge or vaginal spermicide + a male or female condom) Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner) Patient is willing to avoid pregnancies during the study and up to 06 months after the last dose of study drug by use of an effective method of permitted contraception or abstinence.
• Patients having negative pregnancy test.

Exclusion Criteria

• Patients will be excluded from the study, if they meet any of the following criteria: 1. Patients who have a history of hypersensitivity or idiosyncratic reactions to a conventional or novel liposomal formulation of Doxorubicin HCl and its excipients. 2. Prior Doxorubicin (or other anthracyclines) exposure that would result in a total lifetime exposure of 550 mg/m2 or more after four cycles of treatment. 3. Patients who require any dose modifications (Dose other than 50 mg/m2) 4. Have received treatment with radiation therapy, chemotherapy, immunotherapy in less than 4 weeks prior to study entry (6 weeks for nitrosoureas or Mitomycin C) 5. If any patient whose weight changes during the study requiring a ± 5% dose adjustment will be discontinued from the study and excluded from the analysis. 6. If any signs or symptoms of extravasation have occurred, the infusion should be immediately terminated and the patient will be discontinued from the study and excluded from the analysis. 7. Known active brain metastasis including leptomeningeal involvement (patients with brain metastases can only be enrolled if they are treated and stable for >8 weeks and who currently do not require steroid or radiation therapy) 8. Clinically significant Pre-existing toxicity by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria. Mild to moderate Pre-existing toxicity can be allowed only if in the opinion of investigator, it will not require dose modification, will not interfere with the study assessment and will not pose undue safety concerns to the patient. (“Palmar– plantar erythrodysesthesia†and “Stomatitis†of grade 2 and above requires dose modification, hence not allowed). 9. Patients with significantly impaired hepatic or renal function. 10. Significant history or current evidence of chronic.
• infectious, cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic (endocrine), hematological, gastrointestinal, immunological or psychiatric diseases, or organ dysfunction. 11. Laboratory parameters: Patients with ANC < 1500/mm3 Platelet count < 100,000/mm3 Hemoglobin < 9.0 g/dl Bilirubin >2.5 x ULN or if any dose modification required due to abnormal bilirubin levels Alkaline phosphatase, ALT, AST> 2.5 x ULN For other laboratory parameters, the patient can be included if the values are clinically non-significant in the opinion of investigator. 12. Patients with any of the following cardiac conditions: Left ventricular ejection fraction (LVEF) <50 % as determined by ECHO Clinically significant QTc prolongation, Uncontrolled arrhythmias, Acute Ischemia, or other significant abnormalities as determined by ECG. Prior history of Unstable angina in past 06 months. Prior history of Myocardial infarction within the past 06 months. New York State Heart Association (NYHA) class II-IV heart failure. Any other cardiac illness that could lead to a safety risk to the patient in case of enrolment in the study. 13. Pregnant or lactating woman. 14. Females of childbearing potential unwilling to use acceptable contraception (as identified in the protocol) throughout the trial and for 6 months after the last dose of study drug. 15. Use of strong hepatic enzyme modifying drugs (like Phenytoin, Carbamazepine, Barbiturates, Ketoconazole, Itraconazole, Clarithromycin, Erythromycin, Ritonavir, Indinavir, Nelfinavir, Saquinavir, Nefazodone, Diltiazem, Verapamil, Rifampicin and Cyclosporine) in the previous 30 days before the study. 16. Have major surgery, other than diagnostic surgery, within 4 weeks prior to study entry. 17. Patients who have participated in another clinical trial within 90 days of study start. 18. Donation of more than 350 ml of blood within 90 days prior to receiving the first dose of IMP for the current study. 19. Have seizure disorders requiring anticonvulsant therapy. 20. Have known infection with human immunodeficiency virus (HIV I and II antibodies), Hepatitis B or Hepatitis C. 21. Have an active, uncontrolled bacterial, viral, fungal, or other opportunistic infections requiring systemic therapy. 22. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, P. carinii or other microorganism if under treatment with myelotoxic drugs. 23. Poorly controlled hypertension or diabetes. 24. Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments. 25. History of alcohol dependence, alcohol abuse, drug abuse or addiction with any recreational drug within the past one year. 26. Patients who have consumed caffeine and /or xanthine containing products (i.e. coffee, tea, chocolate, and caffeine-containing sodas, colas, etc.), tobacco containing products for at least 48.00 hours prior to check-in. 27. Patients who have consumed alcohol, grape fruit juice or its products 48 hours before dosing. 28. Clinically significant cardiac, liver or kidney disease.

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the bioequivalence of Doxorubicin Hydrochloride Liposome	Pharmacokinetic sampling shall occur within 02 hours pre-dose, 0.00 and post dose | at 00.17, 00.33, 00.50, 00.67, 00.83, | 01.00, 01.08, 01.25, 01.50, 01.75, 02.00, 03.00, 04.00, 06.00, 08.00, 12.00, 24.00, 48.00, 96.00, 144.00, 192.00,240.00, 288.00 and 336.00 hours.
concentrate for solution for infusion 2 mg/mL at a dose of 50mg/m2 of Emcure	Pharmacokinetic sampling shall occur within 02 hours pre-dose, 0.00 and post dose | at 00.17, 00.33, 00.50, 00.67, 00.83, | 01.00, 01.08, 01.25, 01.50, 01.75, 02.00, 03.00, 04.00, 06.00, 08.00, 12.00, 24.00, 48.00, 96.00, 144.00, 192.00,240.00, 288.00 and 336.00 hours.
Pharmaceuticals Ltd., India, compared to that of Caelyx 2 mg/mL concentrate for	Pharmacokinetic sampling shall occur within 02 hours pre-dose, 0.00 and post dose | at 00.17, 00.33, 00.50, 00.67, 00.83, | 01.00, 01.08, 01.25, 01.50, 01.75, 02.00, 03.00, 04.00, 06.00, 08.00, 12.00, 24.00, 48.00, 96.00, 144.00, 192.00,240.00, 288.00 and 336.00 hours.
solution for infusion of Janssen-Cilag	Pharmacokinetic sampling shall occur within 02 hours pre-dose, 0.00 and post dose | at 00.17, 00.33, 00.50, 00.67, 00.83, | 01.00, 01.08, 01.25, 01.50, 01.75, 02.00, 03.00, 04.00, 06.00, 08.00, 12.00, 24.00, 48.00, 96.00, 144.00, 192.00,240.00, 288.00 and 336.00 hours.
International NV, Belgium., in female patients with advanced ovarian cancer	Pharmacokinetic sampling shall occur within 02 hours pre-dose, 0.00 and post dose | at 00.17, 00.33, 00.50, 00.67, 00.83, | 01.00, 01.08, 01.25, 01.50, 01.75, 02.00, 03.00, 04.00, 06.00, 08.00, 12.00, 24.00, 48.00, 96.00, 144.00, 192.00,240.00, 288.00 and 336.00 hours.
injection under fasting condition.	Pharmacokinetic sampling shall occur within 02 hours pre-dose, 0.00 and post dose | at 00.17, 00.33, 00.50, 00.67, 00.83, | 01.00, 01.08, 01.25, 01.50, 01.75, 02.00, 03.00, 04.00, 06.00, 08.00, 12.00, 24.00, 48.00, 96.00, 144.00, 192.00,240.00, 288.00 and 336.00 hours.

Secondary Outcome Measures

Name	Time	Method
To monitor the safety and tolerability of a single dose administered in female	patients with advanced ovarian cancer who have failed a first-line platinum-based

Trial Locations

Locations (26)

Aman Hospital; 🇮🇳 Vadodara, GUJARAT, India

Dr. B Borooah Cancer Institute; 🇮🇳 Kamrup, ASSAM, India

HCG Cancer Centre; 🇮🇳 Ahmadabad, GUJARAT, India

HCG Cancer Centre (Sun Pharma Road); 🇮🇳 Vadodara, GUJARAT, India

HCG Manavata Cancer Centre; 🇮🇳 Nashik, MAHARASHTRA, India

Health Point Hospital; 🇮🇳 Kolkata, WEST BENGAL, India

Hindu Mission Hospital; 🇮🇳 Chennai, TAMIL NADU, India

IPGME & R Oncology Department; 🇮🇳 Kolkata, WEST BENGAL, India

K.R. Hospital, MMC &RI; 🇮🇳 Mysore, KARNATAKA, India

Kailash Cancer Hospital & Research Centre; 🇮🇳 Vadodara, GUJARAT, India

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Aman Hospital

🇮🇳Vadodara, GUJARAT, India

Dr Vibha Naik

Principal investigator

9825029085

vibhanaik64@yahoo.com