A Phase 3, Randomized, Open-Label, Comparative Bridging Study of CAELYX® Versus Topotecan HCl in Subjects With Epithelial Ovarian Carcinoma Following Failure of First-Line, Platinum-Based Chemotherapy
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Enrollment
- 32
- Primary Endpoint
- Number of Participants With Progression-free Survival Incidence at Week 24
Study Overview
Brief Summary
The purpose of this study is to compare the effectiveness between CAELYX and topotecan hydrochloride (HCl) in Chinese participants with recurrent epithelial ovarian carcinoma following failure of first-line, platinum-based chemotherapy, who have received no more than one prior platinum-based regimen therapy.
Detailed Description
This is an open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance), comparative bridging study (a supplemental study which performs to provide data of effectiveness, safety, and dosage to compare two study medications in a new region). The study consists of 3 phases: screening phase (30 days before administration of study medication), treatment phase, and follow up phase (every 8 weeks for tumor assessment until disease progression or death, or until the study completion, whichever is earlier and every 3 months after disease progression for overall survival and for anti-tumor therapy for a minimum of 1 year). In the treatment phase, approximately 120 eligible participants will be categorized prospectively for platinum-sensitivity (sensitive versus refractory) and bulky disease (presence versus absence). Later on participants will be randomly assigned either to experimental arm (CAELYX: administer on Day 1 of each cycle) or control arm (topotecan HCl: administer on Day 1 to Day 5 of each cycle). Treatment will continue until disease progression occurs and may continue for at least 2 cycles after confirmed complete response (disappearance of all target lesions). On average, it is expected that participants will continue treatment for approximately 3 to 6 cycles in experimental arm (CAELYX) or 4 to 8 cycles in Control arm (topotecan HCl). Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, echocardiogram (or multiple gated acquisition scans), vital signs, and physical examination which will be monitored throughout the study. The total duration of the study will be approximately 23 months.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histological diagnosed with epithelial ovarian carcinoma with measurable disease
- •Recurrent epithelial ovarian carcinoma or disease progression following failure of first-line, platinum-based chemotherapy with no more than one prior platinum based regimen therapy
- •Adequate laboratory values of bone marrow function, renal function, liver function, and echocardiogram tests
- •Agrees to use protocol-defined effective contraception. A woman must agree not to donate eggs (ova, oocytes) for the purpose of assisted reproduction
- •Disease-free from prior malignancies for more than 5 years with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
Exclusion Criteria
- •Females who are pregnant or breast feeding or planning to become pregnant while enrolled in this study or within 1 year after the last dose of study medication
- •Myocardial infarct within 6 months before enrollment, class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
- •Uncontrolled systemic infection that requires systemic anti-infective treatment
- •Prior therapy with CAELYX or topotecan HCl
- •Prior chemotherapy within 28 days of first dose of study medication (or 42 days if participant has received a nitrosourea or mitomycin)
Arms & Interventions
CAELYX
Participants will receive CAELYX 50 mg per square meter intravenously on Day 1 of each cycle as: 60 to 90-minute infusion to the participants not undergoing pharmacokinetic (PK) evaluation and 90-minute infusion to the participants undergoing PK evaluation.
Intervention: CAELYX (Drug)
Topotecan hydrochloride (HCl)
Participants will receive topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Intervention: Topotecan HCl (Drug)
Outcomes
Primary Outcomes
Number of Participants With Progression-free Survival Incidence at Week 24
Time Frame: Week 24
Progression-free survival incidence was be measured as number of participants who were progression-free and alive. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20 percent (%) increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Secondary Outcomes
- Duration of Progression-free Survival(1 year after the last dose (24 weeks) administration)
- Number of Participants With Response(Up to Week 24)
- Time to Response(Up to Week 24)
- Duration of Response(Up to 1 year of last dose (Week 24) administration)
- Health-related Quality of Life Assessment (HQL)(Day 1 of each cycle of study medication and Week 4 after last dose of study medication)
- Area Under the Plasma Concentration of CAELYX(0 hour, 30 minutes, 90 minutes, 2 hours, 4 hours, 8 hours, 12 hours, Day 2, Day 3, Day 5, Day 8, and Day 11 for Cycle 1 and Cycle 2)
- Number of Participants With Overall Survival(Week 4 after the last dose of the study medication and approximately up to 1 year after the disease progression or completion of the study treatment or death, whichever is earlier)
- Time to Reach the Maximum Plasma Concentration of CAELYX(0 hour, 30 minutes, 90 minutes, 2 hours, 4 hours, 8 hours, 12 hours, Day 2, Day 3, Day 5, Day 8, and Day 11 for Cycle 1 and Cycle 2)
- Maximum Plasma Concentration of CAELYX(0 hour, 30 minutes, 90 minutes, 2 hours, 4 hours, 8 hours, 12 hours, Day 2, Day 3, Day 5, Day 8, and Day 11 for Cycle 1 and Cycle 2)
- Apparent Terminal Elimination Half-life of Plasma Concentration of CAELYX(0 hour, 30 minutes, 90 minutes, 2 hours, 4 hours, 8 hours, 12 hours, Day 2, Day 3, Day 5, Day 8, and Day 11 for Cycle 1 and Cycle 2)
- Apparent Terminal Elimination Rate Constant of Plasma Concentration of CAELYX(0 hour, 30 minutes, 90 minutes, 2 hours, 4 hours, 8 hours, 12 hours, Day 2, Day 3, Day 5, Day 8, and Day 11 for Cycle 1 and Cycle 2)
- Systemic Clearance of Plasma Concentration of CAELYX(0 hour, 30 minutes, 90 minutes, 2 hours, 4 hours, 8 hours, 12 hours, Day 2, Day 3, Day 5, Day 8, and Day 11 for Cycle 1 and Cycle 2)
- Apparent Volume of Distribution of Plasma Concentration of CAELYX(0 hour, 30 minutes, 90 minutes, 2 hours, 4 hours, 8 hours, 12 hours, Day 2, Day 3, Day 5, Day 8, and Day 11 for Cycle 1 and Cycle 2)
- Number of Participants With Adverse Events(Up to 30 days after the last dose of study medication)