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

• Sponsor: Xian-Janssen Pharmaceutical Ltd. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01840943
• Collaborator: (none)
• Enrollment: 32
• Locations: 7
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Epithelial Ovarian Cancer	Drug: CAELYX; Drug: Topotecan HCl	Phase 3

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
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jun 1, 2013
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: CAELYX; 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.
Active Comparator: 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.	Drug: Topotecan HCl; 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.

Outcome Measures

Primary Outcome Measures

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

1. Duration of Progression-free Survival [1 year after the last dose (24 weeks) administration]

   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.

2. Number of Participants With Response [Up to Week 24]

   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.

3. Time to Response [Up to Week 24]

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

4. Duration of Response [Up to 1 year of last dose (Week 24) administration]

   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.

5. Health-related Quality of Life Assessment (HQL) [Day 1 of each cycle of study medication and Week 4 after last dose of study medication]

   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.

6. 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]

   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.

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

14. Number of Participants With Adverse Events [Up to 30 days after the last dose of study medication]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Beijing		China
2		Chang Sha		China
3		Guangzhou		China
4		Jinan		China
5		Nanjing		China
6		Nanning		China
7		Wuhan		China

Sponsors and Collaborators

• Xian-Janssen Pharmaceutical Ltd.

Investigators

• Study Director: Xian-Janssen Pharmaceutical Ltd., China Clinical Trial, Xian-Janssen Pharmaceutical Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Xian-Janssen Pharmaceutical Ltd.
• ClinicalTrials.gov Identifier: NCT01840943
• Other Study ID Numbers: CR100654; DOXILOVC3001
• First Posted: Apr 26, 2013
• Last Update Posted: Dec 23, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Xian-Janssen Pharmaceutical Ltd.: Epithelial ovarian cancer; Recurrent epithelial ovarian carcinoma; Carcinoma; Malignancy; Ovarian carcinoma; CAELYX; Topotecan hydrochloride; Topotecan; Platinum-based regimen chemotherapy; Chinese patients
• Additional relevant MeSH terms: Carcinoma; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Topotecan

Study Results

Participant Flow

Pre-assignment Detail	Out of 32 participants screened, 26 were randomized to study treatment.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Period Title: Overall Study
STARTED	14	12
COMPLETED	1	0
NOT COMPLETED	13	12

Baseline Characteristics

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)	Total
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.	Total of all reporting groups
Overall Participants	14	12	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.1 (4.97)	51.6 (8.32)	54.0 (6.96)
Sex: Female, Male (Count of Participants)
Female	14 100%	12 100%	26 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat population included (mITT) included all randomized participants.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	14	12
Number [participants]	6 42.9%	2 16.7%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	14	12
Median (95% Confidence Interval) [weeks]	NA	24.6

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	14	12
Complete Response (CR)	0 0%	0 0%
Partial Response (PR)	5 35.7%	3 25%
Stable Disease (SD)	4 28.6%	6 50%
Progression Disease (PD)	1 7.1%	1 8.3%
Not Evaluable (NE)	4 28.6%	2 16.7%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants.Time to response was analyzed for participants who achieved response.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	5	3
Median (Full Range) [weeks]	16.0	16.0

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants. Duration of response was analyzed for participants who achieved response.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	5	3
Median (95% Confidence Interval) [weeks]	NA	9.3

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure as the study was early terminated.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	0	0

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The mITT population included all randomized participants.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	14	12
Death	1 7.1%	0 0%
Still alive	0 0%	0 0%
Early termination: due to lost to follow up	4 28.6%	4 33.3%
Early termination: due to withdraw of consent	5 35.7%	6 50%
Other	4 28.6%	2 16.7%

8. Secondary Outcome

Title	Maximum Plasma Concentration of CAELYX
Time Frame	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

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure as the study was early terminated.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	0	0

9. Secondary Outcome

Title	Time to Reach the Maximum Plasma Concentration of CAELYX
Time Frame	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

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure as the study was early terminated.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	0	0

10. Secondary Outcome

Title	Area Under the Plasma Concentration of CAELYX
Time Frame	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

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure as the study was early terminated.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	0	0

11. Secondary Outcome

Title	Apparent Terminal Elimination Half-life of Plasma Concentration of CAELYX
Time Frame	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

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure as the study was early terminated.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	0	0

12. Secondary Outcome

Title	Apparent Terminal Elimination Rate Constant of Plasma Concentration of CAELYX
Time Frame	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

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure as the study was early terminated.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	0	0

13. Secondary Outcome

Title	Systemic Clearance of Plasma Concentration of CAELYX
Time Frame	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

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure as the study was early terminated.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	0	0

14. Secondary Outcome

Title	Apparent Volume of Distribution of Plasma Concentration of CAELYX
Time Frame	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

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure as the study was early terminated.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	0	0

15. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	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.
Time Frame	Up to 30 days after the last dose of study medication

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants.

Arm/Group Title	CAELYX	Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.	Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
Measure Participants	14	12
TEAEs	12 85.7%	12 100%
TESAEs	1 7.1%	1 8.3%

Adverse Events

Time Frame	Up to 30 days after the last dose of study medication
Adverse Event Reporting Description	Safety population included all randomized participants.
Arm/Group Title	CAELYX		Topotecan Hydrocloride (HCl)
Arm/Group Description	Participants received 50 milligram per square meters (mg/m^2) of Caelyx as a 90-minute or 60 to 90-minute intravenous infusion every 4 weeks.		Participants received topotecan HCl 1.25 mg per square meter per day, intravenously for 30-minutes duration, on Day 1 to Day 5 of each cycle.
All Cause Mortality
	CAELYX		Topotecan Hydrocloride (HCl)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CAELYX		Topotecan Hydrocloride (HCl)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)		1/12 (8.3%)
Infections and infestations
Pulmonary tuberculosis	1/14 (7.1%)		0/12 (0%)
Investigations
Platelet count decreased	0/14 (0%)		1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	CAELYX		Topotecan Hydrocloride (HCl)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/14 (85.7%)		12/12 (100%)
Blood and lymphatic system disorders
Anemia	5/14 (35.7%)		11/12 (91.7%)
Leukopenia	5/14 (35.7%)		2/12 (16.7%)
Neutropenia	5/14 (35.7%)		1/12 (8.3%)
Thrombocytopenia	1/14 (7.1%)		2/12 (16.7%)
Neutrophilia	1/14 (7.1%)		0/12 (0%)
Gastrointestinal disorders
Vomiting	5/14 (35.7%)		8/12 (66.7%)
Nausea	6/14 (42.9%)		5/12 (41.7%)
Constipation	2/14 (14.3%)		1/12 (8.3%)
Mouth ulceration	3/14 (21.4%)		0/12 (0%)
Stomatitis	3/14 (21.4%)		0/12 (0%)
Abdominal distension	1/14 (7.1%)		1/12 (8.3%)
Abdominal pain	0/14 (0%)		2/12 (16.7%)
Diarrhoea	1/14 (7.1%)		1/12 (8.3%)
Abdominal pain upper	0/14 (0%)		1/12 (8.3%)
Gastrointestinal pain	0/14 (0%)		1/12 (8.3%)
Ileus	0/14 (0%)		1/12 (8.3%)
General disorders
Pyrexia	1/14 (7.1%)		1/12 (8.3%)
Fatigue	0/14 (0%)		1/12 (8.3%)
Irritability	1/14 (7.1%)		0/12 (0%)
Immune system disorders
Anaphylactic reaction	1/14 (7.1%)		0/12 (0%)
Hypersensitivity	0/14 (0%)		1/12 (8.3%)
Infusion related reaction	1/14 (7.1%)		0/12 (0%)
Infections and infestations
Upper respiratory tract infection	2/14 (14.3%)		0/12 (0%)
Folliculitis	1/14 (7.1%)		0/12 (0%)
Herpes zoster	1/14 (7.1%)		0/12 (0%)
Pulmonary tuberculosis	1/14 (7.1%)		0/12 (0%)
Vaginal infection	1/14 (7.1%)		0/12 (0%)
Investigations
Leukocytosis	1/14 (7.1%)		0/12 (0%)
White blood cell count decreased	6/14 (42.9%)		10/12 (83.3%)
Neutrophil count decreased	6/14 (42.9%)		9/12 (75%)
Platelet count decreased	0/14 (0%)		6/12 (50%)
Alanine aminotransferase increased	2/14 (14.3%)		1/12 (8.3%)
Aspartate aminotransferase increased	3/14 (21.4%)		0/12 (0%)
Weight decreased	1/14 (7.1%)		1/12 (8.3%)
Blood albumin decreased	1/14 (7.1%)		0/12 (0%)
Lymphocyte percentage decreased	0/14 (0%)		1/12 (8.3%)
Platelet count increased	0/14 (0%)		1/12 (8.3%)
White blood cell count increased	0/14 (0%)		1/12 (8.3%)
Metabolism and nutrition disorders
Decreased appetite	0/14 (0%)		1/12 (8.3%)
Hyperglycaemia	1/14 (7.1%)		0/12 (0%)
Hypoalbuminaemia	0/14 (0%)		1/12 (8.3%)
Psychiatric disorders
Insomnia	0/14 (0%)		1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	2/14 (14.3%)		1/12 (8.3%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	5/14 (35.7%)		0/12 (0%)
Dermatitis	1/14 (7.1%)		0/12 (0%)
Dermatitis acneiform	1/14 (7.1%)		0/12 (0%)
Purpura	1/14 (7.1%)		0/12 (0%)
Rash	1/14 (7.1%)		0/12 (0%)
Rash maculo-papular	1/14 (7.1%)		0/12 (0%)
Skin hyperpigmentation	1/14 (7.1%)		0/12 (0%)

Limitations/Caveats

The study was terminated early as the total number of participants treated in this study was low and only descriptive analysis was used for efficacy and safety evaluation.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.