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

Back to results

Primary Purpose

Status

Terminated

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

CAELYX

Topotecan HCl

About this trial

This is an interventional treatment trial for Epithelial Ovarian Cancer focused on measuring Epithelial ovarian cancer, Recurrent epithelial ovarian carcinoma, Carcinoma, Malignancy, Ovarian carcinoma, CAELYX, Topotecan hydrochloride, Topotecan, Platinum-based regimen chemotherapy, Chinese patients

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

CAELYX

Topotecan hydrochloride (HCl)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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).

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.

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.

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.

Maximum Plasma Concentration of CAELYX

Time to Reach the Maximum Plasma Concentration of CAELYX

Area Under the Plasma Concentration of CAELYX

Apparent Terminal Elimination Half-life of Plasma Concentration of CAELYX

Apparent Terminal Elimination Rate Constant of Plasma Concentration of CAELYX

Systemic Clearance of Plasma Concentration of CAELYX

Apparent Volume of Distribution of Plasma Concentration of CAELYX

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.

Full Information

NCT ID

NCT01840943

First Posted

March 18, 2013

Last Updated

November 17, 2015

Sponsor

Xian-Janssen Pharmaceutical Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT01840943

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Terminated

Why Stopped

the study was terminated due to medication supply issue from current manufacturer

Study Start Date

June 2013 (undefined)

Primary Completion Date

May 2014 (Actual)

Study Completion Date

August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Xian-Janssen Pharmaceutical Ltd.

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epithelial Ovarian Cancer

Keywords

Epithelial ovarian cancer, Recurrent epithelial ovarian carcinoma, Carcinoma, Malignancy, Ovarian carcinoma, CAELYX, Topotecan hydrochloride, Topotecan, Platinum-based regimen chemotherapy, Chinese patients

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CAELYX

Arm Type

Experimental

Arm Description

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.

Arm Title

Topotecan hydrochloride (HCl)

Arm Type

Active Comparator

Arm Description

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 Type

Drug

Intervention Name(s)

CAELYX

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Topotecan HCl

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of Participants With Progression-free Survival Incidence at Week 24

Description

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.

Time Frame

Week 24

Secondary Outcome Measure Information:

Title

Duration of Progression-free Survival

Description

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.

Time Frame

1 year after the last dose (24 weeks) administration

Title

Number of Participants With Response

Description

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.

Time Frame

Up to Week 24

Title

Time to Response

Description

It is calculated as the day of randomization to the first observation of a durable response (the first of the 2 confirmatory measurements).

Time Frame

Up to Week 24

Title

Duration of Response

Description

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.

Time Frame

Up to 1 year of last dose (Week 24) administration

Title

Health-related Quality of Life Assessment (HQL)

Description

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.

Time Frame

Day 1 of each cycle of study medication and Week 4 after last dose of study medication

Title

Number of Participants With Overall Survival

Description

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.

Time Frame

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

Title

Maximum Plasma Concentration of CAELYX

Time Frame