Trial Outcomes & Findings for Second-Line Therapy Study For Potentially Platinum-Sensitive Relapsed Ovarian Cancer (NCT NCT00316173)

Last Updated: 2012-11-27

Results Overview

Overall response rate, as determined by radiologic evaluation (utilizing the World Health Organization \[WHO\] criteria and/or physical examination was measured. Complete response (CR: complete disappearance of all lesions), partial response (PR: \>50% decrease in the measurements of the largest lesions with no appearance of new lesions), stable disease (SD: no change in tumor size for at least 8 weeks) and progressive disease (PD: \>25% increase in measurements of lesions or appearance of new lesions).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

77 participants

Primary outcome timeframe

From start of treatment to evidence of CR or PR (up to 39.3 weeks).

Results posted on

2012-11-27

Participant Flow

The run-in phase was conducted to find a safe dose of drug, before the treatment phase of the study began. Different doses were given to 22 participants (enrolled a few at a time) to find the safest dose. Once the safe dose was found, 55 new participants were enrolled in the treatment phase, and all were to start their treatment at this safe dose.

Participant milestones

Participant milestones
Measure	Dose-finding Phase Starting dose of 2.0 milligrams (mg)/square meter (m2) topotecan (Days 1 and 8, every 21 days) and area under the curve (AUC) 5 carboplatin (Day 1 every 21 days)	Activity Assessment Phase Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Run-in Phase STARTED	22	0
Run-in Phase COMPLETED	15	0
Run-in Phase NOT COMPLETED	7	0
Treatment Phase STARTED	0	55
Treatment Phase COMPLETED	0	13
Treatment Phase NOT COMPLETED	0	42

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose-finding Phase Starting dose of 2.0 milligrams (mg)/square meter (m2) topotecan (Days 1 and 8, every 21 days) and area under the curve (AUC) 5 carboplatin (Day 1 every 21 days)	Activity Assessment Phase Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Run-in Phase Adverse Event	1	0
Run-in Phase Protocol Violation	1	0
Run-in Phase Study Follow-up Stopped	5	0
Treatment Phase Adverse Event	0	1
Treatment Phase Lack of Efficacy	0	3
Treatment Phase Lost to Follow-up	0	3
Treatment Phase Withdrawal by Subject	0	1
Treatment Phase Study Follow-up Stopped	0	34

Baseline Characteristics

Second-Line Therapy Study For Potentially Platinum-Sensitive Relapsed Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose-finding Phase n=22 Participants Starting dose of 2.0 milligrams (mg)/square meter (m2) topotecan (Days 1 and 8, every 21 days) and area under the curve (AUC) 5 carboplatin (Day 1 every 21 days)	Activity Assessment Phase n=55 Participants Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.	Total n=77 Participants Total of all reporting groups
Age Continuous	63.8 years STANDARD_DEVIATION 10.94 • n=5 Participants	62.2 years STANDARD_DEVIATION 11.13 • n=7 Participants	62.6 years STANDARD_DEVIATION 11.03 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	55 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized White	19 participants n=5 Participants	48 participants n=7 Participants	67 participants n=5 Participants
Race/Ethnicity, Customized Missing	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Number of participants with the indicated ECOG Performance Status Grade 0	15 participants n=5 Participants	42 participants n=7 Participants	57 participants n=5 Participants
Number of participants with the indicated ECOG Performance Status Grade 1	7 participants n=5 Participants	9 participants n=7 Participants	16 participants n=5 Participants
Number of participants with the indicated ECOG Performance Status Grade 2	0 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants

PRIMARY outcome

Timeframe: From start of treatment to evidence of CR or PR (up to 39.3 weeks).

Population: Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug

Outcome measures

Outcome measures
Measure	Activity Assessment Phase n=55 Participants Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Number of Participants With the Indicated Response Complete response	6 participants
Number of Participants With the Indicated Response Partial response	11 participants
Number of Participants With the Indicated Response Stable disease	20 participants
Number of Participants With the Indicated Response Progressive disease	7 participants
Number of Participants With the Indicated Response Not evaluable	11 participants

SECONDARY outcome

Timeframe: From start of treatment to evidence of PR or CR (up to 39.3 weeks)

Population: All participants who showed a tumor response (CR or PR).

Time to response was calculated as the time from start of treatment until first evidence of partial response (PR; \>50% decrease in the measurements of the largest lesions with no appearance of new lesions) or complete response (CR; complete disappearance of all lesions).

Outcome measures

Outcome measures
Measure	Activity Assessment Phase n=17 Participants Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Time to Response	6.57 weeks Interval 5.86 to 12.57

SECONDARY outcome

Timeframe: From time of PR or CR to disease progression/death (up to 56.0 weeks)

Population: All participants who showed a tumor response (CR or PR).

Duration of response was calculated as the time from first documented PR or CR until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was "censored".

Outcome measures

Outcome measures
Measure	Activity Assessment Phase n=17 Participants Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Duration of Response	42.64 weeks Interval 36.14 to 47.14

SECONDARY outcome

Timeframe: From start of treatment to disease progression/death (up to 67.7 weeks)

Population: Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug

Progression-free survival (PFS) was calculated as the time from the start of treatment until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was "censored". Although "Time to Disease Progression" was stated as an endpoint in the protocol, the definition given in the protocol (and used in the study) was that of "PFS". As such, "PFS" was measured, not "Time to Disease Progression".

Outcome measures

Outcome measures
Measure	Activity Assessment Phase n=55 Participants Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Progression-free Survival	44.29 weeks Interval 36.14 to 52.14

SECONDARY outcome

Timeframe: From start of treatment to death (up to 110.4 weeks).

Population: Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug

The number of participants who died from the start of treatment to follow-up was calculated. For participants who did not die, the date of last contact was used. The word used for such participants was "censored".

Outcome measures

Outcome measures
Measure	Activity Assessment Phase n=55 Participants Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Number of Participants Who Died From the Start of Treatment to Follow-up Died	8 participants
Number of Participants Who Died From the Start of Treatment to Follow-up Censored	47 participants

SECONDARY outcome

Timeframe: Baseline to end of study (up to 54.7 weeks).

Population: Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug

CA-125 is a "tumor marker", found in greater concentration in tumor cells than other cells of the body. Participants were classed as responders if their CA-125 level at the end of study was 50% or less of baseline. In addition, a confirmatory sample (taken at least 28 days after the first sample) must have also been 50% or less of baseline.

Outcome measures

Outcome measures
Measure	Activity Assessment Phase n=55 Participants Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
The Number of Participants Classified as Responders in Cancer Antigen 125 (CA-125)	23 participants

SECONDARY outcome

Timeframe: From start of treatment to disease progression/death

Population: Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug

Although "Time to Disease Progression" was stated as an endpoint in the protocol, the definition given in the protocol (and used in the study) was that of "Progression-free Survival". As such, "Progression-free Survival" was measured, not "Time to Disease Progression". See the outcome measure entitled "Progression-free Survival" for data pertaining to time to disease progression.

Outcome measures

Outcome data not reported

Adverse Events

Dose-finding Phase

Serious events: 6 serious events

Other events: 20 other events

Deaths: 0 deaths

Activity Assessment Phase

Serious events: 12 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Dose-finding Phase n=22 participants at risk Starting dose of 2.0 milligrams (mg)/square meter (m2) topotecan (Days 1 and 8, every 21 days) and area under the curve (AUC) 5 carboplatin (Day 1 every 21 days)	Activity Assessment Phase n=55 participants at risk Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Blood and lymphatic system disorders Anemia	4.5% 1/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	3.6% 2/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Blood and lymphatic system disorders Neutropenia	4.5% 1/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
General disorders Pyrexia	4.5% 1/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Vascular disorders Thrombosis	4.5% 1/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	0.00% 0/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Infections and infestations Diverticulitis	4.5% 1/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	0.00% 0/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Infections and infestations Urinary tract infection	4.5% 1/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	0.00% 0/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Vascular disorders Vena cava thrombosis	4.5% 1/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	0.00% 0/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Gastrointestinal disorders Enterovesical fistula	4.5% 1/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	0.00% 0/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Immune system disorders Hypersensitivity	4.5% 1/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	0.00% 0/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	4.5% 1/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	0.00% 0/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	3.6% 2/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Gastrointestinal disorders Abdominal pain	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	3.6% 2/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Cardiac disorders Angina pectoris	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Immune system disorders Drug hypersensitivity	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to soft tissue	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Vascular disorders Peripheral embolism	0.00% 0/22 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.	1.8% 1/55 Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.