CTRI/2023/03/050946 [Registered on: 21/03/2023] Trial Registered Prospectively
Last Modified On:
05/10/2023
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
This is a Bioequivalence Study between formulations of Doxorubicin Hydrochloride Liposome Injection 20 mg/10 mL (50 mg/m2 dose) for treating Patients with Advanced Ovarian Cancer.
Scientific Title of Study
A Multicenter, Open Label, Balanced, Randomized, Two-Treatment, Two-Period, Two-Sequence, Single Dose, Crossover, Bioequivalence Study between two formulations of Doxorubicin Hydrochloride Liposome Injection 20 mg/10 mL (50 mg/m2 dose) (Doxorubicin-Test compared with Doxorubicin-Reference) in Patients with Advanced Ovarian Cancer.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
0270-22,Version: 2.1,Date: 29-Nov-2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Department of clinical research, Room no. NA, Tosham Road, Near South Bypass Crossing Hisar - 125005, India. Hisar HARYANA
9896539142
drlovenish@gmail.com
Dr Sourav Mishra
AIIMS, Bhubaneswar
AIIMS, Sijua Patnapada, Bhubaneswar, 751019, Odisha, India. Khordha ORISSA
7008651823
drskmishra1984@gmail.com
Dr Mukesh Chandre
Ashirwad Hospital & Research Centre
Department of clinical research, Room no. NA, Maratha Section, Near Jijamata Udhyan, Ulhasnagar - 421004 Thane MAHARASHTRA
9595160424
mukeshchandre@gmail.com
Dr K Velavan
Erode Cancer Centre
Department of clinical research, Room no. 1/393, Velavan Nagar, Peru Erode TAMIL NADU
9842334222
kvels@redifmail.com
Dr Vijay Mohobia
Government Medical College & Hospital
Department of clinical research, Room no. NA, Department of Radiation Oncology, Government Medical College & Hospital, Medical Square Nagpur - 440003 Nagpur MAHARASHTRA
9881287465
drvijay-mahobia@yahoo.com
Dr L K Priyadarshini
HCG City cancer Center
Department of clinical research, Room no. NA, 33-25-33, CH Venkata, Gopala Krishnaiah Street, Suryaraopeta Krishna ANDHRA PRADESH
9642611888
Priyadarshini006@gmail.com
Dr Asma Pathan
Indrayani Hospital & Cancer Institute
Department of clinical research, Room no. NA, Alandi - Chakan Road, Alandi, Devachi, Tal. Khed, Dist. Pune, Maharashtra - 412105 Pune MAHARASHTRA
8007167716
Asmapathan124@gmail.com
Dr Om Prakash Sharma
JNU Institute of Medical Science & Research Centre
Department of clinical research, Room no. NA, Near new RTO office, Jagatpura, Jaipur, Rajasthan Jaipur RAJASTHAN
7615931030
clinicalresearch@jnujaipur.ac.in
Dr Prakash S S
K. R. Hospital, Mysore Medical Collage and Research Institute & Hospital
Department of clinical research, Room no. NA, Irwin Road, Mysore, Karnataka- 570001, India Mysore KARNATAKA
9901000559
prakashyesyes@yahoo.com
Dr Murli Subramanium
Medstar Speciality Hospital
Department of clinical research, Room no. 641/1/17 31, Kodigehalli Main Road, Sahakar Nagar, Sanjeevani Nagar, Bangalore - 560092, India. Bangalore KARNATAKA
9945813327
medstarclinicalresearch@gmail.com
Dr Kadarla Krishna
MNJ Institute of oncology & Regional Cancer Center
Department of clinical research, Room no. 11-5, 399 Red Hills, Lakdikapul, Hyderabad, Telangana 500004 Hyderabad TELANGANA
9441775222
mnjiorckrishnakadarla@gmail.com
Dr Rachan Shetty
Omega Hospital
Department of clinical research, Room no. NA, Omega Hospital, Mahauger Circle, Kankanady Dakshina Kannada KARNATAKA
9008753317
drrachanshetty.medoncology@gmail.com
Dr R K kajla
S P Medical College & AG Hospitals
Department of clinical research, Room no. NA, Bikaner- 334003 Rajasthan Bikaner RAJASTHAN
9782300231
drrkkajla@gmail.com
Dr Ghanashyam Biswas
Sparsh Hospital & Critical Care
Department of clinical research, Room no. A/407, Saheed Nagar, Bhubaneswar, Odisha, 751007 Khordha ORISSA
9937500878
drgbiswas@gmail.com
Dr Ankit Patel
Sunshine Global Hospital
Department of clinical research, Room no. NA, Sunshine Global Hospital, Beside Big Bazar, Gaurav Path, Dumas Road, Surat Surat GUJARAT
Aadhar Institutional Ethics Committee, Dr. Lovinesh Goyal
Approved
Ashirwad Hospital & Research Centre,Dr. Mukesh Chandre
Approved
Ethics Committee, S.P. Medical College, Bikaner, Dr. R K Kajla
Approved
IEC - Erode Cancer Centre, Dr. K. Velavan
Approved
IEC - GMC, Dr. Vijay Mahobia
Submittted/Under Review
IEC-MMC and RI and Associated Hospital, Mysore Medical College and Research Institute, Dr. Prakash S. S.
Approved
Institutional Ethics Committee AIIMS Bhubaneswar, Dr. Sourav Mishra
Approved
Institutional Ethics Committee JNU Institute for Medical Sciences and Research Centre, Dr. Om Prakash Sharma
Approved
Institutional Ethics Committee Sunshine Global Hospital, Dr. Ankit Patel
Approved
Institutional Ethics Committee, Sparsh Hospital, Dr. Ghanashyam Biswas
Approved
Institutional Ethics Committee- HCG Curie CCC, Dr. L K Priyadarshini
Approved
Medstar Speciality Hospital Ethics Committee, Dr. Murli Subramanium
Approved
MNJ Institute of Oncology & Regional Cancer Center Ethics Committee, Dr. Kadarla Krishna
Approved
Narsimha Saraswati Medical Foundation Ethics Committee, Dr. Asma Pathan
Approved
Omega Ethical Committee, Dr. Rachan Shetty
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C569||Malignant neoplasm of unspecifiedovary,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Doxorubicin Hydrochloride Liposome Injection
Dose Formulation-Liposomal formulation,Dosage Level(s) 50 mg/m2,Route of Administration -Intravenous
Comparator Agent
Doxorubicin Hydrochloride Liposome Injection
Dose Formulation-Liposomal formulation,Dosage Level(s) 50 mg/m2,Route of Administration -Intravenous
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Female
Details
1 Participant must sign an ICF indicating that the participant understands the purpose of, and procedures required for the study as described in Appendix 10.1.3 and in this protocol and is willing to participate in the study.2 Female participant must be 18 to 75 years of age (both inclusive), at the time of signing the informed consent.3 Participant with documented advanced ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy AND who are already receiving or scheduled to start the monotherapy.4 Life expectancy of more than or equal to 12 weeks at screening visit.5 An Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 at screening visit.6 Participant should have recovered from any toxic effects of previous chemotherapy as judged by the Investigator. Participants who are already receiving doxorubicin hydrochloride liposome injection at a dose of 50 mg/m2 should not require dose reduction(s) in next planned cycle in the study due to toxicity as per the Prescribing Information (PI).7 A participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:a Is not a woman of childbearing potential (WOCBP)b Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of less than 1 per cent per year), with low user dependency when used consistently and correctly, as described in Appendix 4 during the intervention period and for at least six months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during the study and for at least six months after the last dose of study intervention. The investigator should evaluate the effectiveness and the potential for contraceptive method failure (eg, noncompliance, recently initiated) of the contraceptive method in relationship to the first dose of study intervention.• A WOCBP must have a negative highly sensitive serum pregnancy test at screening and
urine pregnancy test within 24 hours before the first dose of study intervention.• If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum
pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.• Additional requirements for pregnancy testing during and after study intervention are located in Section 8.3.6.• The investigator is responsible for review of medical history, menstrual history, and
recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.8 Participant with adequate hematologic,renal and liver function at screening visit.a Absolute Neutrophil Count (ANC) more than or equal to 1500/mm b Platelet count more than or equal to 75000/mm c Hemoglobin more than or equal to 9.0 g/dL d Estimated Glomerular Filtration Rate (eGFR) of more than or equal to 50 mL/min/1.73 m2 by the CKD-EPI formula e Total Bilirubin less than or equal to 1.2 mg/dL (≤4 × ULN for liver metastasis)f AST and ALT less than or equal to 2.5 × ULN (less than or equal to 4 × ULN for liver metastasis)
ExclusionCriteria
Details
Any potential participant who meets any of the following criteria will be excluded from participating
in the study:1 Documented medical history of clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances or any other medical condition(s) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being)or that could prevent, limit, or confound the protocol-specified assessments.2 Known allergies, hypersensitivity, or intolerance to any of the investigational interventions, or components/ excipients thereof (refer to the PI), or drug or other allergy which is clinically significant in the opinion of the investigator that contraindicates participation in the study.3 Prior doxorubicin exposure that would result in a total lifetime exposure of 550 mg/m2 or more after four cycles of treatment.4 Current active systemic opportunistic infection based on clinical assessment.5 Had major surgical procedure and will not have fully recovered from surgical procedure, or has surgical procedure planned during the time the participant is expected to participate in the study.NOTE: Participants with any planned surgical procedure under local anaesthesia only may participate if they agree to seek prior approval from the investigator and such planned procedure is not expected to prevent, limit, or confound the protocol-specified assessments as assessed by the investigator.6 Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of investigational intervention.7 Positive hepatitis C antibody test result at screening or within 3 months prior to starting investigational intervention.NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA test is obtained 8 Has known human immunodeficiency virus (HIV) seropositive status, or positive HIV antibody test at screening.9 History of malignancy except disease under study within the past 3 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years; carcinoma in situ of the cervix; or malignancy, which is considered cured with minimal risk of recurrence.10 Leptomeningeal disease and known CNS disease (baseline brain imaging is not required for the eligibility assessment), except for treated asymptomatic CNS metastases, provided all of the following criteria are met: a Only supratentorial metastases allowed (ie, no metastases to midbrain, pons, medulla, or spinal cord).b Completed treatment (eg, whole brain radiation treatment [WBRT], stereotactic radiosurgery,or equivalent) at least 14 days prior to the first dose of the study intervention.c No evidence of new or enlarging brain metastases or hemorrhage confirmed by post-treatment repeat brain imaging (using the same modality) performed at least 3 weeks after pre-treatment brain imaging.d Are neurologically stable without the need for steroids for at least 14 days before first dose of the study intervention per local site assessment (anticonvulsants at a stable dose are allowed).11 Participant with known history or current symptoms of any of the following clinically significant cardiac conditions:a Unstable angina or myocardial infarction within the past 6 months.b New York Heart Association (NYHA) cardiac disease (Class III or greater) within past 6 months c High-risk uncontrolled arrythmias within past 6 months d Clinically significant pericardial disease within past 6 months
e Electrocardiographic evidence of acute ischemic or active conduction system abnormalities within past 6 months f Any other cardiac illness that could lead to a safety risk to the study participant within past 6 months g Participant with a known left ventricular ejection fraction (LVEF) less than 50percent by echocardiogram
or multigated acquisition scan (MUGA) within last 28 days before randomization h Study participants with known coronary artery disease, congestive heart failure not meeting the above criteria, must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.12 Received an investigational intervention or used an invasive investigational medical device
within 30 days or 5 half-lives prior to baseline, whichever is longer, prior to baseline.13 Intended use of prohibited medications as mentioned in Section 6.9. Specific medications listed may be allowed.14 Documentation of confirmed novel coronavirus infection (COVID-19) at Visit 2 before randomization.15 Positive test result(s)for urine alcohol or drugs of abuse (including barbiturates, opiates,cocaine, cannabinoids, amphetamines and benzodiazepines) at the time of check-in of Period-I, which is not due to current medical therapy
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To characterize the pharmacokinetic profile and to assess the bioequivalence of Doxorubicin-Test relative to Doxorubicin-Reference in participants with advanced ovarian cancer.
Total Sample Size="48" Sample Size from India="48" 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
N/A
Date of First Enrollment (India)
22/03/2023
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="0" Months="6" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
NIL
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is Multicentric, Open Label, Balanced, Randomized, Two-Treatment, Two-Period, Two-Sequence, Single Dose, Crossover, Bioequivalence Study between two formulations of Doxorubicin Hydrochloride Liposome Injection 20 mg/10 mL (50 mg/m2 dose) (Doxorubicin-Test compared with Doxorubicin-Reference) in Patients with Advanced Ovarian Cancer