A Study to Compare CAELYX With Topotecan HCL in Patients With Recurrent Epithelial Ovarian Carcinoma Following Failure of First-Line, Platinum-Based Chemotherapy

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Epithelial Ovarian Cancer

Intervention / Treatment
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* Drug: CAELYX
* Drug: Topotecan HCl


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAELYX<br>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. | Drug: CAELYX<br>* CAELYX 50 mg per square meter will be administered 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 for PK evaluation.<br>|
| Active Comparator: Topotecan hydrochloride (HCl)<br>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. | Drug: Topotecan HCl<br>* Topotecan 1.25 mg per square meter per day will be administered, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Progression-free Survival Incidence at 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. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Progression-free Survival | It was calculated as the time, in weeks, from the day of randomization until documented disease progression or death due to any cause, whichever occurs first using a Kaplan-Meier curve for PFS. | 1 year after the last dose (24 weeks) administration | 
| Number of Participants With Response | Response rate was measured as number of participants with at least a durable response: Complete response (CR) or partial response (PR). Complete response is defined as the disappearance of all target lesions. Partial response is defined as at least a 30 percentage decrease in the sum of diameters of target lesions. Stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Progression in disease is defined as at least a 20% increase in the sum of diameters of target lesions. Not evaluable participants were those who were not analyzed. The reference of the baseline sum of diameters of lesions was considered. | Up to Week 24 | 
| Time to Response | It is calculated as the day of randomization to the first observation of a durable response (the first of the 2 confirmatory measurements). | Up to Week 24 | 
| Duration of Response | It is calculated as the first observation of a durable response (the first of the 2 confirmatory measurements) to the first observation of disease progression or death due to any cause. | Up to 1 year of last dose (Week 24) administration | 
| Health-related Quality of Life Assessment (HQL) | Calculation of each HQL domain scale will be performed according to the scoring guidelines for each of the HQL measures. The HQL analyses will include scales measuring physical functioning, pain, nausea, fatigue, and global quality of life. Each item is measured on a scale of 0 to 3, where 0 = no impact on quality of life and 3 = extreme impact on quality of life. | Day 1 of each cycle of study medication and Week 4 after last dose of study medication | 
| Number of Participants With Overall Survival | Number of Participants With Overall survival were categorized as number of 1) Deaths, 2) Still alive, 3) Early termination from the study due to lost to follow up, 4) Early termination from the study due to withdraw of consent, 5) Other. Overall survival is defined as the time interval from randomization to death from any cause. | 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grade 3 (Severe) events are symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events are Symptoms causing inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. | Up to 30 days after the last dose of study medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoma, Epithelial ovarian cancer, Recurrent epithelial ovarian carcinoma, Malignancy, Ovarian carcinoma, CAELYX, Topotecan hydrochloride, Topotecan, Platinum-based regimen chemotherapy, Chinese patients