Bioavailability study of DOXIL/CAELYX (2 mg/mL) in patients with advanced or refractory ovarian or breast cancer.
- Conditions
- Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
- Registration Number
- CTRI/2023/08/056252
- Lead Sponsor
- Baxter Healthcare Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
1. Be a man or woman aged from 18 to 75 years, inclusive.
2. Patients with advanced or refractory ovarian or breast cancer, expected to require at least 2 cycles of DOXIL or CAELYX therapy at Screening, are eligible for treatment per this study protocol. This includes:
a. Histologically or cytologically confirmed advanced ovarian cancer recurrence after platinum-based chemotherapy.
b. Histologically or cytologically confirmed metastatic breast cancer recurrence after approved life prolonging therapies.
3. Life expectancy greater than 6 months based on the clinical evaluation by the investigator at the time of Screening.
4. Eastern Cooperative Oncology Group (ECOG) Performance status 0 to 2, inclusive.
5. Recovered from the acute toxicity of any prior treatment (exemptions: alopecia, neuropathy Grade I, Hemoglobin greater than or equal to 9 g per dL Grade 2). All toxicities from prior treatment should return to baseline or Grade I.
6. Prior (or other anthracyclines) at cumulative doxorubicin dose of less than or equal to 240 mg per m2 (calculated using doxorubicin equivalent doses: 1 mg doxorubicin equal to1 mg DOXIL or CAELYX equal to 2.2 mg mitoxantrone equal to 2 mg idarubicin equal to 0.5 m daunorubicin equal to 0.5 mg epirbucin).2 Patients without any prior anthracycline exposure can also be included.
7. Adequate liver function as determined by serum total bilirubin levels less than or equal to 1.2 mg per dL, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels less than or equal to 2.5 x ULN and alkaline phosphatase less than 2.5 × ULN, in case of subjects with bone metastasis less than 5× ULN.
8. Adequate bone marrow function, as determined by an absolute neutrophil count (ANC) greater than or equal to 1500 per mm3 (or greater than or equal to 1.5 x 109 per L), a platelet count greater than or equal to 100,000 per mm3 (or greater than or equal to 100 x 109 per L), and a hemoglobin level greater than or equal to 9 g per dL (or greater than or equal to 90 g per L), in the absence of transfusion requirements or cytokine support for at least 7 days prior to Investigational Product (IP) administration.
9. Adequate renal function (30-156 mL per min), as determined by multiplying estimated glomerular filtration rate (e-GFR) by the BSA and dividing the value by 1.73m2 (refer to Appendix 4).
10. Left ventricular ejection fraction within normal limits of the institution, as determined by multiple uptake gated acquisition (MUGA) or echocardiography.
11. Female patients (of childbearing potential) must use medically acceptable methods of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patches, intrauterine devices, the double-barrier method, male partner sterilization) before enrollment, throughout the study and for at least 8 months after the last DOXIL or CAELYX infusion.
12. Male patients must agree to use an adequate contraception method as deemed appropriate by the Investigator and always use condoms when sexually active during the study. Medically acceptable methods of contraception that may be used by the patient and or his partner include oral contraceptives, contraceptive injections, contraceptive patches, intrauterine devices, the double-barrier method, and surgical sterilization (vasectomy or tubal ligation) for minimally 8 months after the last administration of
Subjects will be excluded from the study based on the following criteria:
1.Positive history of known brain metastases or leptomeningeal disease. Patients with brain metastases can only be enrolled if the following conditions are all met:
a.Brain metastases have been treated and stable for > 4 weeks ( > 2 weeks after SRS/Cyberknife).
b.No evidence for progression or hemorrhage after treatment.
c.Steroid treatment was discontinued at least 2 weeks prior to the first administration of DOXIL/CAELYX.
d.Enzyme inducing anti-epileptic drugs were discontinued at least 4 weeks before first administration of DOXIL/CAELYX.
2.Has a history of hypersensitivity reaction to doxorubicin HCl or other components of DOXIL/CAELYX.
3.Has a history of prior or concomitant malignancy that requires other active treatment.
4.Require any antineoplastic treatment while on the study (including therapy with another agent, radiation therapy, and/or surgical resection).
5.Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed greater than or equal to 2 weeks prior to the first dose; greater than or equal to 4 weeks for whole brain radiotherapy). Chemotherapy regimens with delayed toxicity within the last 3 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks or 5 half-lives (whichever is shorter).
6.Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of DOXIL/CAELYX.
7.Impaired cardiac function including any of the following conditions within the past 6 months:
a.Unstable angina
b.QTc prolongation (QTcB > 450 millisecond [males] or > 470 millisecond [females] at screening or prior to 1st dose of IP administration) or with known history of Torsades de Points, or family members with sudden cardiac deaths, or other significant electrocardiogram (ECG) abnormalities3
c.Coronary artery bypass graft surgery
d.Symptomatic peripheral vascular disease
e.Myocardial infarction
f.NYHA class II-IV heart failure
g.Severe uncontrolled ventricular arrhythmias
h.Clinically significant pericardial disease
i.Electrocardiographic evidence of acute ischemic or active conduction system abnormalities
j.Patients with evidence of abnormal cardiac conduction (e.g. bundle branch block or heart block) are eligible if their disease has been stable for the past 6 months
k.Severe uncontrolled arrhythmias
8.Has an infection that is either uncontrolled, clinically important (occurred within 4 weeks prior to first dose of study agent), or requiring current systemic IV treatment.
9.Patients with active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, P. carinii or other microorganism if under treatment with myelotoxic drugs
10.Patient has received a diagnosis of COVID-19 (diagnosis less than or equal to 2 months prior to screening and/or symptoms have not resolved).
11.A patient with uncontrolled concurrent illness including, but not limited to, poorly controlled hypertension or diabetes, or psychiatric illness/social situation that may potentially impair the patient’s compliance with study proced
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To demonstrate bioequivalence between DOXIL or CAELYX reference product & test product based on the encapsulated doxorubicin pharmacokinetic (PK) parameters of Cmax, AUC0-t, & AUC0-Infinity in patients with advanced or refractory ovarian or breast cancerTimepoint: Pre-Dose, Day1 (Drug Administration) 15mins,30mins,1hour,1hour30mins,1hour35mins, 1hour45mins,2hour,3hour,4hour,6hour,8hour,Day2(24hour),Day3(48hour),Day5 (96hour),Day8 (168hour),Day11(240hour),Day15(336 hour),Day22(504 hour).
- Secondary Outcome Measures
Name Time Method To demonstrate BE between DOXIL or CAELYX reference product & test product based on the total doxorubicin PK parameters of Cmax, AUC0-t, and AUC0-infinity in patients with advanced or refractory ovarian or breast cancer.Timepoint: Pre-Dose, Day1 (Drug Administration) 15mins,30mins,1hour,1hour30mins,1hour35mins, 1hour45mins,2hour,3hour,4hour,6hour,8hour,Day2(24hour),Day3(48hour),Day5 (96hour),Day8 (168hour),Day11(240hour),Day15(336 hour),Day22(504 hour).