Advanced Solid Tumors
Conditions
Brief summary
The purpose of this study is to find a safe and tolerable dose of Lipotecan® when administered to patients with advanced solid tumors.
Detailed description
Lipotecan® is a drug product of TLC388 HCl, which is a potent camptothecin analog with cytotoxic activities against a variety of human tumor cell lines in vitro and anti-tumor activities in several xenograft models with human tumor cell lines. Structurally, TLC388 HCl is related to other camptothecins, but it has been chemically modified to improve stability and potency, and to minimize toxicities.
Interventions
DRUGLipotecan
Lipotecan IV day 1, 8, 15
Sponsors
Taiwan Liposome Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients defined by age ≥18 years. * Pathologically confirmed advanced solid tumors for which standard therapy proven to provide clinical benefit does not exist or is no longer effective * Evaluable disease, either measurable on imaging or with informative tumor marker(s), by RECIST (Response Evaluation Criteria in Solid Tumors) criteria.
Exclusion criteria
* Pregnancy or lactation. Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrolment. Male and female patients of childbearing potential must agree to use appropriate birth control (barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices) during the entire duration of the study, or the patient must be surgically sterile (with documentation in the patient's medical records). * Previous malignancy, except for non-basal-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix, unless the tumor was treated with curative intent more than 2 years prior to study entry. * Receipt of more than 3 prior regimens of chemotherapy. * Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to baseline. Receipt of radiotherapy to \>25 % of bone marrow. Major surgery within 4 weeks prior to baseline. * Concomitant treatment with, or anticipated use of, pharmaceutical or herbal agents which are potent inhibitors or inducers of cytochrome P450 enzymes unless approved by the Sponsor. * Uncontrolled intercurrent illness that would jeopardize patient safety, interfere with the objectives of the protocol, or limit patient compliance with study requirements, as determined by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Decay Half-Life (t1/2) of TLC-U2 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Maximum Tolerated Dose (MTD) of Lipotecan | First treatment to toxicity up to 42 days | 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. |
| Number of Participants With Adverse Events | an average of 6 months | 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 |
| Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,R-TLC388 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,S-TLC388 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Maximum Observed Dose-normalized Plasma Concentration (Cmax) of Topotecan | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U1 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U2 | 0, 15m, 29m, 33m, 40m, 50m, 1h, 1h30m, 2h, 4h, 8h | 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. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,R-TLC388 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h | 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. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,S-TLC388 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Topotecan | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U1 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U2 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,R-TLC388 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,S-TLC388 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Topotecan | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U1 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U2 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Plasma Decay Half-Life (t1/2) of S,R-TLC388 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Plasma Decay Half-Life (t1/2) of S,S-TLC388 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Plasma Decay Half-Life (t1/2) of Topotecan | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
| Plasma Decay Half-Life (t1/2) of TLC-U1 | 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-tumor Activity | From start of treatment assessed every 2 cycles up to 2.5 years | 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. |
Countries
Taiwan, United States
Participant flow
Recruitment details
The study recruitment period was from Sep 2008 to Dec 2010. Patients were recruited from three US clinical sites and one Taiwan site.
Pre-assignment details
Patients will attend the clinic for a screening visit up to 28 days before receiving, if eligible, the first dose of Lipotecan®.
Participants by arm
| Arm | Count |
|---|---|
| Overall Population Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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
| Characteristic | Overall Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 22 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants |
| Age, Continuous | 60.5 years STANDARD_DEVIATION 11.6 |
| Region of Enrollment Taiwan | 13 participants |
| Region of Enrollment United States | 41 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 54 / 54 |
| serious Total, serious adverse events | 11 / 54 |
Outcome results
Primary
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,R-TLC388
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | 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
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,S-TLC388
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | 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
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U1
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | 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 2.2 |
Primary
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U2
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | 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
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Topotecan
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | 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 1.3 |
Primary
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,R-TLC388
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,R-TLC388 | 1.39 ng/mL | Standard Deviation 3.21 |
Primary
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,S-TLC388
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,S-TLC388 | 2.21 ng/mL | Standard Deviation 5.12 |
Primary
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U1
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U1 | 5.01 ng/mL | Standard Deviation 1.91 |
Primary
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U2
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1h, 1h30m, 2h, 4h, 8h
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U2 | 1.40 ng/mL | Standard Deviation 0.48 |
Primary
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of Topotecan
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Maximum Observed Dose-normalized Plasma Concentration (Cmax) of Topotecan | 0.82 ng/mL | Standard Deviation 0.44 |
Primary
Maximum Tolerated Dose (MTD) 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.
Time frame: First treatment to toxicity up to 42 days
Population: Patients received at least one dose of Lipotecan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Maximum Tolerated Dose (MTD) of Lipotecan | 50 mg/m^2 |
Primary
Number of Participants With Adverse Events
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
Time frame: an average of 6 months
Population: Patients received at least one dose of Lipotecan
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Number of Participants With Adverse Events | 54 participants |
Primary
Plasma Decay Half-Life (t1/2) of S,R-TLC388
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Plasma Decay Half-Life (t1/2) of S,R-TLC388 | 1.08 hour | Standard Deviation 1.77 |
Primary
Plasma Decay Half-Life (t1/2) of S,S-TLC388
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Plasma Decay Half-Life (t1/2) of S,S-TLC388 | 0.75 hour | Standard Deviation 1.18 |
Primary
Plasma Decay Half-Life (t1/2) of TLC-U1
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Plasma Decay Half-Life (t1/2) of TLC-U1 | 3.13 hour | Standard Deviation 1.27 |
Primary
Plasma Decay Half-Life (t1/2) of TLC-U2
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Plasma Decay Half-Life (t1/2) of TLC-U2 | 2.58 hour | Standard Deviation 0.62 |
Primary
Plasma Decay Half-Life (t1/2) of Topotecan
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Plasma Decay Half-Life (t1/2) of Topotecan | 6.05 hour | Standard Deviation 2.71 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,R-TLC388
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,R-TLC388 | 0.47 hour | Standard Deviation 0.3 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,S-TLC388
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,S-TLC388 | 0.47 hour | Standard Deviation 0.3 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U1
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U1 | 0.45 hour | Standard Deviation 0.17 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U2
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U2 | 0.47 hour | Standard Deviation 0.14 |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Topotecan
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.
Time frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Population: Patients complete cycle 1 and 2 treatments without major protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Topotecan | 0.93 hour | Standard Deviation 0.82 |
Secondary
Anti-tumor Activity
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.
Time frame: From start of treatment assessed every 2 cycles up to 2.5 years
Population: Patients received at least one dose of Lipotecan.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Anti-tumor Activity | Complete Response (CR) | 0 participants |
| All Participants | Anti-tumor Activity | Partitial Response (PR) | 0 participants |
| All Participants | Anti-tumor Activity | Stable Disease (SD) | 21 participants |
| All Participants | Anti-tumor Activity | Progression Disease (PD) | 20 participants |
| All Participants | Anti-tumor Activity | No assessment | 13 participants |