Trial Outcomes & Findings for Phase I Study of Intravenous Lipotecan® (TLC388 HCl for Injection) in Patients With Advanced Solid Tumors (NCT NCT00747474)
NCT ID: NCT00747474
Last Updated: 2019-11-18
Results Overview
MTD is the highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity (DLT)). A 3+3 study design was used to determine MTD. The MTD was the highest dose level at which 0 of 3 or 1 of 6 patients experience a DLT, with the next higher dose having at least 2 of 3 or 2 of 6 patients experiencing a DLT.
COMPLETED
PHASE1
54 participants
First treatment to toxicity up to 42 days
2019-11-18
Participant Flow
The study recruitment period was from Sep 2008 to Dec 2010. Patients were recruited from three US clinical sites and one Taiwan site.
Patients will attend the clinic for a screening visit up to 28 days before receiving, if eligible, the first dose of Lipotecan®.
Participant milestones
| Measure |
Cohort 1 (1.5 mg/m^2)
Participants received 1.5 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 2 (3 mg/m^2)
Participants received 3 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 3 (6 mg/m^2)
Participants received 6 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 4 (9 mg/m^2)
Participants received 9 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 5 (13.5 mg/m^2)
Participants received 13.5 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 6 (20 mg/m^2)
Participants received 20 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 7 (30 mg/m^2)
Participants received 30 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 8 (40 mg/m^2)
Participants received 40 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 9 (35 mg/m^2)
Participants received 35 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 10 (40 mg/m^2)
Participants received 40 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 11 (50 mg/m^2)
Participants received 50 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 12 (60 mg/m^2)
Participants received 60 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cohort 1 (1.5 mg/m^2) Period
STARTED
|
3
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 1 (1.5 mg/m^2) Period
COMPLETED
|
3
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 1 (1.5 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 2 (3 mg/m^2) Period
STARTED
|
0
|
4
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 2 (3 mg/m^2) Period
COMPLETED
|
0
|
4
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 2 (3 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 3 (6 mg/m^2) Period
STARTED
|
0
|
0
|
3
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 3 (6 mg/m^2) Period
COMPLETED
|
0
|
0
|
3
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 3 (6 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 4 (9 mg/m^2) Period
STARTED
|
0
|
0
|
0
|
4
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 4 (9 mg/m^2) Period
COMPLETED
|
0
|
0
|
0
|
4
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 4 (9 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 5 (13.5 mg/m^2) Period
STARTED
|
0
|
0
|
0
|
0
|
4
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 5 (13.5 mg/m^2) Period
COMPLETED
|
0
|
0
|
0
|
0
|
4
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 5 (13.5 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 6 (20 mg/m^2) Period
STARTED
|
0
|
0
|
0
|
0
|
0
|
4
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 6 (20 mg/m^2) Period
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
4
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 6 (20 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 7 (30 mg/m^2) Period
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
4
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 7 (30 mg/m^2) Period
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
4
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 7 (30 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 8 (40 mg/m^2) Period
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
6
|
0
|
0
|
0
|
0
|
|
Cohort 8 (40 mg/m^2) Period
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
5
|
0
|
0
|
0
|
0
|
|
Cohort 8 (40 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Cohort 9 (35 mg/m^2) Period
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
4
|
0
|
0
|
0
|
|
Cohort 9 (35 mg/m^2) Period
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
4
|
0
|
0
|
0
|
|
Cohort 9 (35 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 10 (40 mg/m^2) Period
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
7
|
0
|
0
|
|
Cohort 10 (40 mg/m^2) Period
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
7
|
0
|
0
|
|
Cohort 10 (40 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 11 (50 mg/m^2) Period
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
5
|
0
|
|
Cohort 11 (50 mg/m^2) Period
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
5
|
0
|
|
Cohort 11 (50 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Cohort 12 (60 mg/m^2) Period
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
6
|
|
Cohort 12 (60 mg/m^2) Period
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
6
|
|
Cohort 12 (60 mg/m^2) Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1 (1.5 mg/m^2)
Participants received 1.5 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 2 (3 mg/m^2)
Participants received 3 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 3 (6 mg/m^2)
Participants received 6 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 4 (9 mg/m^2)
Participants received 9 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 5 (13.5 mg/m^2)
Participants received 13.5 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 6 (20 mg/m^2)
Participants received 20 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 7 (30 mg/m^2)
Participants received 30 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 8 (40 mg/m^2)
Participants received 40 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 9 (35 mg/m^2)
Participants received 35 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 10 (40 mg/m^2)
Participants received 40 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 11 (50 mg/m^2)
Participants received 50 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
Cohort 12 (60 mg/m^2)
Participants received 60 mg/m\^2/dose, given as a 30 minute IV infusion on Days 1, 8 and 15 of a 28 day cycle. Each 28 day (4 week) period will constitute one cycle of treatment. Dose escalation of Lipotecan® will be based upon the safety and tolerability data from the first treatment cycle in each patient and determined by Safety Review Committee (SRC) for this study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cohort 8 (40 mg/m^2) Period
with efficacy and continued treatment
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Phase I Study of Intravenous Lipotecan® (TLC388 HCl for Injection) in Patients With Advanced Solid Tumors
Baseline characteristics by cohort
| Measure |
Overall Population
n=54 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
32 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
22 Participants
n=5 Participants
|
|
Age, Continuous
|
60.5 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
41 participants
n=5 Participants
|
|
Region of Enrollment
Taiwan
|
13 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: First treatment to toxicity up to 42 daysPopulation: Patients received at least one dose of Lipotecan.
MTD is the highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity (DLT)). A 3+3 study design was used to determine MTD. The MTD was the highest dose level at which 0 of 3 or 1 of 6 patients experience a DLT, with the next higher dose having at least 2 of 3 or 2 of 6 patients experiencing a DLT.
Outcome measures
| Measure |
All Participants
n=54 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Maximum Tolerated Dose (MTD) of Lipotecan
|
50 mg/m^2
|
PRIMARY outcome
Timeframe: an average of 6 monthsPopulation: Patients received at least one dose of Lipotecan
Number of participants with AEs that occurred during treatment and follow-up period (30 days after last treatment). Drug-related AEs and SAEs were followed until resolved or stabilized. AEs were classified by the investigator according to severity graded using CTCAE version 3.0 and relationship to study drug. The severity scale is: Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening or disabling, Grade 5= Death related to AE
Outcome measures
| Measure |
All Participants
n=54 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Number of Participants With Adverse Events
|
54 participants
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,R-TLC388
|
1.39 ng/mL
Standard Deviation 3.21
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,S-TLC388
|
2.21 ng/mL
Standard Deviation 5.12
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of Topotecan
|
0.82 ng/mL
Standard Deviation 0.44
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U1
|
5.01 ng/mL
Standard Deviation 1.91
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1h, 1h30m, 2h, 4h, 8hPopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U2
|
1.40 ng/mL
Standard Deviation 0.48
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8hPopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,R-TLC388
|
0.47 hour
Standard Deviation 0.30
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,S-TLC388
|
0.47 hour
Standard Deviation 0.30
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Topotecan
|
0.93 hour
Standard Deviation 0.82
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U1
|
0.45 hour
Standard Deviation 0.17
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U2
|
0.47 hour
Standard Deviation 0.14
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,R-TLC388
|
0.70 hr*ng/mL
Standard Deviation 1.63
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,S-TLC388
|
1.04 hr*ng/mL
Standard Deviation 2.44
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Topotecan
|
3.59 hr*ng/mL
Standard Deviation 1.30
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U1
|
7.15 hr*ng/mL
Standard Deviation 2.20
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U2
|
2.00 hr*ng/mL
Standard Deviation 0.66
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Plasma Decay Half-Life (t1/2) of S,R-TLC388
|
1.08 hour
Standard Deviation 1.77
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Plasma Decay Half-Life (t1/2) of S,S-TLC388
|
0.75 hour
Standard Deviation 1.18
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Plasma Decay Half-Life (t1/2) of Topotecan
|
6.05 hour
Standard Deviation 2.71
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Plasma Decay Half-Life (t1/2) of TLC-U1
|
3.13 hour
Standard Deviation 1.27
|
PRIMARY outcome
Timeframe: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dosePopulation: Patients complete cycle 1 and 2 treatments without major protocol deviation.
Drug product Lipotecan consists of TLC388 diastereomers (S,S-TLC388 and S,R-TLC388 in 2:1 ratio). Three metabolites as TLC-U1, TLC-U2 and topotecan were identified in rats, dogs and human.
Outcome measures
| Measure |
All Participants
n=48 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Plasma Decay Half-Life (t1/2) of TLC-U2
|
2.58 hour
Standard Deviation 0.62
|
SECONDARY outcome
Timeframe: From start of treatment assessed every 2 cycles up to 2.5 yearsPopulation: Patients received at least one dose of Lipotecan.
Patients were evaluated by tumor assessment using RECIST guidelines. Possible evaluations include: Complete Response (CR): disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the size of target lesions. Progressive Disease (PD): at least a 20% increase in the size of target lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Outcome measures
| Measure |
All Participants
n=54 Participants
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.
|
|---|---|
|
Anti-tumor Activity
Complete Response (CR)
|
0 participants
|
|
Anti-tumor Activity
Partitial Response (PR)
|
0 participants
|
|
Anti-tumor Activity
Stable Disease (SD)
|
21 participants
|
|
Anti-tumor Activity
Progression Disease (PD)
|
20 participants
|
|
Anti-tumor Activity
No assessment
|
13 participants
|
Adverse Events
Overall Population
Serious adverse events
| Measure |
Overall Population
n=54 participants at risk
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle.
|
|---|---|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Blood and lymphatic system disorders
ANAEMIA
|
3.7%
2/54 • Number of events 3 • 32 months
|
|
General disorders
ASTHENIA
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Cardiac disorders
CARDIO-RESPIRATORY ARREST
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
3.7%
2/54 • Number of events 2 • 32 months
|
|
Infections and infestations
CYSTITIS KLEBSIELLA
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Gastrointestinal disorders
DIARRHOEA
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Gastrointestinal disorders
ENTEROVESICAL FISTULA
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Infections and infestations
ESCHERICHIA URINARY TRACT INFECTION
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Musculoskeletal and connective tissue disorders
FLANK PAIN
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Renal and urinary disorders
HAEMATURIA
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Vascular disorders
HYPERTENSION
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
3.7%
2/54 • Number of events 2 • 32 months
|
|
Infections and infestations
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
1.9%
1/54 • Number of events 2 • 32 months
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Infections and infestations
PYELONEPHRITIS
|
1.9%
1/54 • Number of events 1 • 32 months
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
3.7%
2/54 • Number of events 3 • 32 months
|
|
Infections and infestations
URINARY TRACT INFECTION
|
3.7%
2/54 • Number of events 2 • 32 months
|
Other adverse events
| Measure |
Overall Population
n=54 participants at risk
Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle.
|
|---|---|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
5.6%
3/54 • Number of events 4 • 32 months
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
18.5%
10/54 • Number of events 19 • 32 months
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
11.1%
6/54 • Number of events 7 • 32 months
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
5.6%
3/54 • Number of events 3 • 32 months
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
7.4%
4/54 • Number of events 4 • 32 months
|
|
Blood and lymphatic system disorders
ANAEMIA
|
63.0%
34/54 • Number of events 106 • 32 months
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
9.3%
5/54 • Number of events 6 • 32 months
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
11.1%
6/54 • Number of events 8 • 32 months
|
|
Investigations
BLOOD ALKALINE PHOSPHATASE INCREASED
|
5.6%
3/54 • Number of events 4 • 32 months
|
|
Gastrointestinal disorders
CONSTIPATION
|
25.9%
14/54 • Number of events 20 • 32 months
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
13.0%
7/54 • Number of events 7 • 32 months
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
22.2%
12/54 • Number of events 17 • 32 months
|
|
Gastrointestinal disorders
DIARRHOEA
|
27.8%
15/54 • Number of events 25 • 32 months
|
|
Nervous system disorders
DIZZINESS
|
14.8%
8/54 • Number of events 8 • 32 months
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
7.4%
4/54 • Number of events 5 • 32 months
|
|
General disorders
FATIGUE
|
40.7%
22/54 • Number of events 48 • 32 months
|
|
Musculoskeletal and connective tissue disorders
FLANK PAIN
|
5.6%
3/54 • Number of events 3 • 32 months
|
|
Metabolism and nutrition disorders
HYPERCALCAEMIA
|
5.6%
3/54 • Number of events 3 • 32 months
|
|
Metabolism and nutrition disorders
HYPOALBUMINAEMIA
|
13.0%
7/54 • Number of events 7 • 32 months
|
|
Metabolism and nutrition disorders
HYPOCALCAEMIA
|
13.0%
7/54 • Number of events 9 • 32 months
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
7.4%
4/54 • Number of events 4 • 32 months
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
13.0%
7/54 • Number of events 7 • 32 months
|
|
Metabolism and nutrition disorders
HYPOPHOSPHATAEMIA
|
5.6%
3/54 • Number of events 3 • 32 months
|
|
Vascular disorders
HYPOTENSION
|
5.6%
3/54 • Number of events 5 • 32 months
|
|
Psychiatric disorders
INSOMNIA
|
9.3%
5/54 • Number of events 5 • 32 months
|
|
Investigations
INTERNATIONAL NORMALISED RATIO INCREASED
|
5.6%
3/54 • Number of events 3 • 32 months
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
24.1%
13/54 • Number of events 23 • 32 months
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
9.3%
5/54 • Number of events 8 • 32 months
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
9.3%
5/54 • Number of events 5 • 32 months
|
|
Gastrointestinal disorders
NAUSEA
|
37.0%
20/54 • Number of events 30 • 32 months
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
27.8%
15/54 • Number of events 54 • 32 months
|
|
General disorders
OEDEMA PERIPHERAL
|
16.7%
9/54 • Number of events 9 • 32 months
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
7.4%
4/54 • Number of events 4 • 32 months
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
7.4%
4/54 • Number of events 8 • 32 months
|
|
General disorders
PYREXIA
|
7.4%
4/54 • Number of events 4 • 32 months
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
24.1%
13/54 • Number of events 31 • 32 months
|
|
Infections and infestations
URINARY TRACT INFECTION
|
9.3%
5/54 • Number of events 5 • 32 months
|
|
Gastrointestinal disorders
VOMITING
|
25.9%
14/54 • Number of events 24 • 32 months
|
|
Investigations
WEIGHT DECREASED
|
5.6%
3/54 • Number of events 3 • 32 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60