CTRI/2023/01/048827 [Registered on: 09/01/2023] Trial Registered Prospectively
Last Modified On:
21/08/2023
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
The Study will be conducted in Patients with Advanced Ovarian Cancer or Metastatic Breast 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 (2 mg/mL) [Doxopeg® manufactured
by FAPASA - Farmaceutica Paraguay S.A. and registered by Zodiac Produtos Farmacêuticos S.A.
(test formulation) and Caelyx® manufactured by Janssen Pharmaceutica NV (reference
formulation)] in Patients with Advanced Ovarian Cancer or Metastatic Breast Cancer.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
0063-22 ,Version - 01, Date :20-July-2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Department of Radiotherapy,Room No. NA,AIIMS, Plot No. 2, Sector 20, Mihan, Nagpur-441108 Nagpur MAHARASHTRA
9405744685
drvandana.radonco@gmail.com
Dr Mangesh Korde
Chopda Medicare & Research Centre Pvt. Ltd
Department of Clinical Research,Room No.N/A,Chopda Medicare & Research Centre Pvt. Ltd; Magnum Heart Institute, 3/5, Patil Lane No. 1, Laxmi Nagar, Near K.B.H. Vidyalaya, Canada Corner, Nashik-422005, Maharashtra, India Nashik MAHARASHTRA
9028532380
drmangeshkorde@yahoo.in
Dr K Velavan
Erode Cancer Center
Department of Clinical Research,Room No.N/A,Erode Cancer Centre 1/393 Velavan Nagar, Perundurai road, Thindal, Erode-638012 Erode TAMIL NADU
9842334222
kvels@rediffmail.com
Dr KL Priyadarshini
HCG City cancer Center
Department of Clinical Research,Room No.N/A,HCG City cancer centre, 33-25-33, Ch. Venkata kriahnayya street, Suryarao pet, Vijayawada- 520002, Andhra Pradesh, India Krishna ANDHRA PRADESH
9885256059
priyadarshini006@gmail.com
Dr Rajnish Nagarkar
HCG curie City cancer Center
Department of Clinical Research,Room No.N/A,HCG Manavata Cancer Centre, Behind Shivang Auto, Mumbai Naka,Nashik Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Asma Pathan
Indrayani Hospital and Cancer Centre
Department of Clinical Research,Room No.N/A,Indrayani Hospital and Cancer Institute,
Alandi-Chakan road, Alandi, Devachi, Tal-Khed,
Dist- Pune, Maharashtra-412105 Pune MAHARASHTRA
8007167716
Asmapathan124@gmail.com
Dr Prakash S S
K. R. Hospital
Department of Clinical Research,Room No.N/A,Dept. of Surgical Oncology, K R Hospital, Mysore Medical College & Research Institute, Irwin Road, Mysore, Karnataka-570001, India Mysore KARNATAKA
9901000559
prakashyesyes@yahoo.com
Dr Mahesh Kalloli
KLES Dr Prabhakar Kore Hospital & MRC
Department of Clinical Research,Room No.N/A,KLERS Dr Prabhakar Kore Hospital & Medical Research Centre, Nehrunagar Belagavi-590010 Karnataka India Belgaum KARNATAKA
9591358733
mahesh.kalloli@gmail.com
Dr Suraj Pawar
Kolhapur Cancer Centre
Department of Clinical Research,Room No.N/A,Kolhapur Cancer Centre Pvt. Ltd., R.S. 238, Opp. Mayur Petrol Pump, Gokul Shirgaon, Kolhapur-416234 Kolhapur MAHARASHTRA
9822014908
surajpawar2001@yahoo.co.in
Dr Viraj Vijay Borgaonkar
Krupamayi Hospital
Department of Clinical Research,Room No.N/A,Krupamayi Hospitals, "Akshay", Opp. Youth Hostel, Near Baba Petrol Pump, Railway Station road, Aurangabad-431001, Maharahtra. Aurangabad MAHARASHTRA
9736073555
viraj.oncosurge@gmail.com
Dr Rakesh Neve
Lifepoint Hospital
Department of Clinical Research,Room No.N/A,Lifepoint Multispeciality Hospital, 3rd Floor, Clinical Research Department, 145/1, Mumbai-Bangalore Highway, Near Hotel Sayaji, Wakad, Pune-411057, Maharashtra, India Pune MAHARASHTRA
9881143140
rakesh.neve23@gmail.com
Dr Murali Subramaniyan
Medstar Hospital
Department of Clinical Research,Room No.N/A,Medstar Speciality Hospital,#641/17/1/3, Kodigehalli Main Road, Sahakarnagar, Bangalore-560092, Karnataka, India. Bangalore KARNATAKA
9945813327
medstarclinicalresearch@gmail.com
Dr P Radhika
MNJ
Department of Clinical Research,Room No.N/A,MNJ Institute of Oncology & Regional Cancer Center, 3rd Floor, Clinical Trial Room No.11, Red Hills, Hyderabad - 500004 Telangana, India. Hyderabad TELANGANA
9849792682
radhika.parimkayala@gmail.com
Dr Anil Kumar
Oncoville Cancer Institute
Department of clinical Research,Room nO. NA,Oncoville Cancer Hospital & Research Centre, No.4, 80Ft.Road, 7th Block, Nagarbhavi 2nd Stage, Bangalore-560072- Karnataka Bangalore KARNATAKA
9739808502
dranil.onco@gmail.com
Dr RK Kajla
S P Medical College & AG Hospitals
Department of clinical Research,Department of Surgery, S.P. Medical College & AG of Hospitals, Bikaner 334003, Rajasthan Bikaner RAJASTHAN
9782300231
drrkkajla@gmail.com
Dr Aniket Thoke
Sanjivani CBCC Hospital
Department of Clinical Research,Room No.N/A,Sanjeevani CBCC USA Cancer Hospital, Infront of Jain Mandir, dawada, colony pachpedi naka raipur C.G 492001 Raipur CHHATTISGARH
9752929741
drthoke@gmail.com
Dr Bhushan Nemade
Sankal Speciality Hospital
Department of Clinical Research,Room No.N/A,Sankalp Speciality Hospital, Dhanvantari Marg, Vallabh Nagar, Behind Chhan Hotel, Mumbai-Agra Highway, Mumbai Naka, Nashik-422009, Maharashtra, India Nashik MAHARASHTRA
9766126162
drbtnemade@yahoo.co.in
Dr Nirali Trivedi
Shankush Hospital
Department of Clinical Research,Room No.N/A,hankus Hospital, 214, B/h. Divine Child School, Near Shankus Water Park, Baliyasan,Ta & Dist: Mehsan, Gujarat, 382732, India Mahesana GUJARAT
8980008109
nirali_baxi81@yahoo.com
Dr Rajendrasingh Arora
Sujan Surgical Cancer Hospital
Department of Clinical Research,Room No.N/A,Sujan Surgical Cancer Hospital and ACF, 52/B, Main Road Shankar Nagar, Amravati-444605 Amravati MAHARASHTRA
9823097573
dr_rsarora@rediffmail.com
Dr Ankit Patel
Sunshine Global Hospital
Department of Clinical Research,Room No.N/A,Sunshine Global Hospital, Beside big bazar, Gaurav path, Dumas road, Surat, Gujarat, India-395007 Surat GUJARAT
Dose Formulation-Concentrate for solution for infusion,Dosage Level(s)-50 mg/m2,Route of Administration -IV infusion
Intervention
Doxopeg® - Doxorubicin
Hydrochloride Liposome Injection 20 mg/10 mL (2mg/mL)
Dose Formulation -Concentrate for solution for infusion,Dosage Level(s) 50 mg/m2,Route of Administration IV infusion
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Female
Details
Participants are eligible to be included in the study only if all of the following criteria apply:
1 Participant must sign an ICF indicating that the participant understands the purpose of, and
procedures required for the study 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 meeting one of the following criteria-a 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 with liposomal doxorubicin (pegylated) at a dose of 50 mg/m2.
b.Participants with documented metastatic breast cancer AND who are already receiving or
scheduled to start the monotherapy with liposomal doxorubicin (pegylated) at a dose of 50
mg/m2.4 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 liposomal doxorubicin (pegylated)
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 Summary of Product Characteristics (SmPC).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) as defined in Appendix 4
b Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of
more than 1% 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/mm3 b Platelet count more than or equal to 75000/mm3,c Hemoglobin more than or equal to 9.0 g/dL.d Estimated Glomerular Filtration Rate (eGFR) of more than or equal to 30 mL/min/1.73 m2 by the CKD-EPI formula e Total Bilirubin less than 1.2 mg/dLf AST and ALT less than or equal to 2.5 × ULN (less than or equal to 4 × ULN for liver metastasis)9 Participant willing and able to adhere to the lifestyle restrictions specified in this protocol.c Hemoglobin less than or equal to 9.0 g/dL d Estimated Glomerular Filtration Rate (eGFR) of less than or equal to 30 mL/min/1.73 m2
by the CKD-EPI formulae Total Bilirubin less than 1.2 mg/dLf 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 wellbeing) or that could prevent, limit, or confound the protocol-specified assessments.2 Known allergies, hypersensitivity, or intolerance to any of the study interventions, or components/ excipients thereof (refer to the SmPC), or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.3 Prior doxorubicin exposure that would result in a total lifetime exposure of 450 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 havefully recovered from surgical procedure, or has surgical procedure planned during the time the participant is expected to participate in the study.NOTE: Participants with planned surgical procedures to be conducted under local anesthesia may participate.6 Presence of hepatitis B surface antigen (HBsAg) or IgM anti-HBC 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 drug or alcohol abuse according to medical history assessment by investigator
within 1 year before screening.10 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.11 Known CNS disease, except for treated asymptomatic CNS metastases. Baseline brain imaging is not required for the eligibility assessment. Leptomeningeal disease is always an exclusion.12 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 II or greater) within past 6 monthsc 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 monthsf 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 50% 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.13 Received an investigational intervention or used an invasive investigational medical device within 6 months prior to baseline.14 Intended use of prohibited medications within 14 days prior to dosing and during the study.Specific medications listed in Section 6.8 may be allowed.15 Positive Covid-19 RT-PCR test at the time of baseline within 72 hours before hospitalization
Method of Generating Random Sequence
Stratified 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 TEST(Doxopeg® - liposomal doxorubicin)relative to RLD (Caelyx® - liposomal
doxorubicin) in participants with advanced ovarian cancer or metastatic breast cancer
Following pharmacokinetic parameters will be
evaluated for encapsulated doxorubicin and
unencapsulated doxorubicin:
• Cmax and AUC0-t
Secondary Outcome
Outcome
TimePoints
To further characterize the pharmacokinetic profile of TEST (Doxopeg® - liposomal
doxorubicin) relative to RLD (Caelyx® -liposomal doxorubicin) in participants with advanced ovarian cancer or metastatic breast cancer
Following pharmacokinetic parameters will be
evaluated for encapsulated doxorubicin and
unencapsulated doxorubicin:
• AUC0-∞, Tmax, AUC_%Extrap_obs, λz, t1/2, Vd
and Cl
Target Sample Size
Total Sample Size="58" Sample Size from India="58" Final Enrollment numbers achieved (Total)= "74" Final Enrollment numbers achieved (India)="74"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
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 (2 mg/mL) [Doxopeg® manufactured
by FAPASA - Farmaceutica Paraguay S.A. and registered by Zodiac Produtos Farmacêuticos S.A.
(test formulation) and Caelyx® manufactured by Janssen Pharmaceutica NV (reference
formulation)] in Patients with Advanced Ovarian Cancer or Metastatic Breast Cancer.