Bioequivalence Study Comparing Generic to Reference Liposome-Encapsulated Doxorubicin Hydrochloride
- Conditions
- Health Condition 1: C509- Malignant neoplasm of breast of unspecified siteHealth Condition 2: C569- Malignant neoplasm of unspecifiedovary
- Registration Number
- CTRI/2019/05/019051
- Lead Sponsor
- Aine Cunningham
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Suspended
- Sex
- Not specified
- Target Recruitment
- 0
1. Female between 18 and 75 years of age, inclusive.
2. Patients with documented advanced ovarian cancer who have failed a first-line platinum-based chemotherapy regimen OR
3. Patients with documented metastatic breast cancer
4. Having a Body Mass Index (BMI) of at least 17.00 kg/m2
5. Able to understand the investigational nature of this study and give written informed consent prior to the participation in the trial.
6. Recovery from any toxic effects of previous chemotherapy as judged by the Investigator.
7. Able and clinically indicated to receive liposomal formulation of doxorubicin HCl, as specified in the Caelyx Summary of Product Characteristics (SmPC), without exceeding a lifetime cumulative anthracycline dosage of 450 mg/m2 (See for rationale). Prior use of conventional or liposomal doxorubicin formulations, in addition to the use of other anthracyclines/anthracenediones or 5-fluorouracil, should be included in calculations of total lifetime cumulative dose.
8. Able and clinically indicated to receive the recommended minimum 4 courses of a liposomal formulation of doxorubicin HCl either during participation in this study, including infusions prior to enrolling in this study or after completing study participation
9. Eastern Cooperative Oncology Group (ECOG) performance status of <= 2. Any subject who experiences deterioration in ECOG status to 4 during the study should discontinue participation in the study.
10. Life expectancy of > 180 days.
11. Acceptable hematology status:
a. Hemoglobin >= 9 g/dL
b. Absolute neutrophil count (ANC) >= 1500 cells/μL
c. Platelet count >= 75,000 cells/μL
12. Acceptable liver function:
a. Alanine aminotransferase (ALT) <= 2X upper limit of normal (ULN)
b. Aspartate aminotransferase (AST) <= 2X ULN
c. Bilirubin < 1.2 mg/dL
d. Alkaline phosphatase <= 2X ULN
13. Acceptable kidney function
a. Creatinine <= 2X ULN
OR
b. Creatinine clearance >= 60 mL/minute
14. Cardiac ejection fraction >= 50% by echocardiogram (ECHO) within 14 days prior to first dose of Investigational Product.
15. For subjects of childbearing potential, negative serum pregnancy test at screening and negative urine pregnancy test at Cycle 1 Day 0 and Cycle 2 Day 0
16. No history of addiction to any recreational drug or drug dependence or alcohol addiction.
17. All female subjects who are sexually active with a male partner must be willing to use 1 of the following acceptable contraceptive methods throughout the study and for 6 months immediately following the last dose of IP (TEST or RMP):
a. Intrauterine device
b. Double barrier methods (e.g., condom or diaphragm with intra-vaginally applied spermicide)
c. Prescription hormonal contraceptives
d. Sterile male partner (vasectomized >= 6 months prior to IP dosing)
1. Received a liposomal formulation of doxorubicin HCl in the past and had a required dose reduction to below 50 mg/m2, or whose disease has progressed or recurred after treatment with a liposomal formulation of doxorubicin HCl.
2. Prior dose limiting toxicity on pegylated liposomal doxorubicin HCl at 50 mg/m2
3. Prior radiation therapy within the 14 days prior to first dosing of IP.
4. Use of steroids and/or anti-convulsive agents within three months prior to screening (for patients with previously diagnosed brain metastases).
5. Recent (6 month) history of impaired cardiac function and any of
the following conditions (See Caelyx SmPC â?? based on Investigator discretion):
• Unstable angina
• Significant ECG abnormalities
• Coronary artery bypass graft surgery
• Symptomatic peripheral vascular disease
• Myocardial infarction
• New York Heart Association (NYHA) class III-IV heart failure
• Liver disease
• Kidney disease
• Clinically significant pericardial disease
• Electrocardiographic evidence of acute ischemic or active conduction system 1. Received a liposomal formulation of doxorubicin HCl in the past and had a required dose reduction to below 50 mg/m2, or whose disease has progressed or recurred after treatment with a liposomal formulation of doxorubicin HCl.
2. Prior dose limiting toxicity on pegylated liposomal doxorubicin HCl at 50 mg/m2
3. Prior radiation therapy within the 14 days prior to first dosing of IP.
4. Use of steroids and/or anti-convulsive agents within three months prior to screening (for patients with previously diagnosed brain metastases).
5. Recent (6 month) history of impaired cardiac function and any of
the following conditions (See Caelyx SmPC â?? based on Investigator discretion):
• Unstable angina
• Significant ECG abnormalities
• Coronary artery bypass graft surgery
• Symptomatic peripheral vascular disease
• Myocardial infarction
• New York Heart Association (NYHA) class III-IV heart failure
• Liver disease
• Kidney disease
• Clinically significant pericardial disease
• Electrocardiographic evidence of acute ischemic or active conduction system 1. Received a liposomal formulation of doxorubicin HCl in the past and had a required dose reduction to below 50 mg/m2, or whose disease has progressed or recurred after treatment with a liposomal formulation of doxorubicin HCl.
2. Prior dose limiting toxicity on pegylated liposomal doxorubicin HCl at 50 mg/m2
3. Prior radiation therapy within the 14 days prior to first dosing of IP.
4. Use of steroids and/or anti-convulsive agents within three months prior to screening (for patients with previously diagnosed brain metastases).
5. Recent (6 month) history of impaired cardiac function and any of
the following conditions (See Caelyx SmPC â?? based on Investigator discretion):
• Unstable angina
• Significant ECG abnormalities
• Coronary artery bypass graft surgery
• Symptomatic peripheral vascular disease
• Myocardial infarction
• New York Heart Association (NYHA) class III-IV heart failure
• Liver disease
• Kidney disease
• Clinically significant pericardial disea
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the bioequivalence of Tolmarâ??s TEST product (Doxorubicin Hydrochloride Liposomal Injection [2 mg/mL]) concentrate for solution for infusion relative to that of reference medicinal product (RMP), Caelyx (pegylated liposomal doxorubicin hydrochloride (HCl) for injection [2 mg/mL]), concentrate for solution for infusion in subjects with advanced ovarian carcinoma who have failed a first-line platinum-based chemotherapy regimen and/or subjects with metastatic breast cancer.Timepoint: Day 0 Predose 30 ± 5 minutes <br/ ><br>60 to 65 minutes 120 ± 10 minutes 180 ± 10 minutes 240 ± 15 minutes 480 ± 15 minutes 24 ± 1 hr 48 ± 1 hr 96 ± 1 hr 168 ± 2 hrs 240 ± 2 hrs 336 ± 4 hrs 504 ± 4 hrs
- Secondary Outcome Measures
Name Time Method To assess safety and tolerability of Caelyx (RMP) and Tolmar formulation (TEST) in subjects who are exposed to the investigational medicinal productsTimepoint: Day 0 Predose 30 ± 5 minutes <br/ ><br>60 to 65 minutes 120 ± 10 minutes 180 ± 10 minutes 240 ± 15 minutes 480 ± 15 minutes 24 ± 1 hr 48 ± 1 hr 96 ± 1 hr 168 ± 2 hrs 240 ± 2 hrs 336 ± 4 hrs 504 ± 4 hrs