Intravenous Lipotecan (TLC388 HCl for Injection)

Lipotecan

Min-Hsiung Kao

The purpose of this study is to find a safe and tolerable dose of Lipotecan® when administered to patients with advanced solid tumors.

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.

Phase I Study of Intravenous Lipotecan® (TLC388 HCl for Injection) in Patients With Advanced Solid Tumors

A Phase 1 Open-Label, Sequential Dose Escalation Study Investigating the Safety, Tolerability, and Pharmacokinetics of Intravenous Lipotecan® (TLC388 HCl for Injection) When Administered to Patients With Advanced Solid Tumors

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 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

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.

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.

Taiwan Liposome Company

Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle.

Overall Population

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Taiwan

Region of Enrollment

Shu Chi Hsu

Lipotecan was administered intravenously on day 1, 8 and 15 of a 28-day cycle according to the dose assigned.

All Participants

Patients received at least one dose of Lipotecan.

Maximum Tolerated Dose (MTD) of Lipotecan

Complete Response (CR)

Partitial Response (PR)

Stable Disease (SD)

Progression Disease (PD)

No assessment

Anti-tumor Activity

Patients received at least one dose of Lipotecan

Number of Participants With Adverse Events

Patients complete cycle 1 and 2 treatments without major protocol deviation.

Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,R-TLC388

Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,S-TLC388

Maximum Observed Dose-normalized Plasma Concentration (Cmax) of Topotecan

Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U1

Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U2

Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,R-TLC388

Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,S-TLC388

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Topotecan

Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U1

Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U2

Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,R-TLC388

Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,S-TLC388

Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Topotecan

Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U1

Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U2

Plasma Decay Half-Life (t1/2) of S,R-TLC388

Plasma Decay Half-Life (t1/2) of S,S-TLC388

Plasma Decay Half-Life (t1/2) of Topotecan

Plasma Decay Half-Life (t1/2) of TLC-U1

Plasma Decay Half-Life (t1/2) of TLC-U2

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 1 (1.5 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 2 (3 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 3 (6 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 4 (9 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 5 (13.5 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 6 (20 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 7 (30 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 8 (40 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 9 (35 mg/m^2)

Cohort 10 (40 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 11 (50 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 12 (60 mg/m^2)

Cohort 1 (1.5 mg/m^2) Period

Cohort 2 (3 mg/m^2) Period

Cohort 3 (6 mg/m^2) Period

Cohort 4 (9 mg/m^2) Period

Cohort 5 (13.5 mg/m^2) Period

Cohort 6 (20 mg/m^2) Period

Cohort 7 (30 mg/m^2) Period

Cohort 8 (40 mg/m^2) Period

Cohort 9 (35 mg/m^2) Period

Cohort 10 (40 mg/m^2) Period

Cohort 11 (50 mg/m^2) Period

Cohort 12 (60 mg/m^2) Period

Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Administer 40mg of Lipotecan at D1, D8, D15 of each cycles.

Administer 40mg Lipotecan at D1, D8, D15 of each cycle.

Yunlong Tseng

The purpose of this study is to evaluate the safety and efficacy of TLC388 (Lipotecan) as a second line treatment in subjects with advanced Hepatocellular Carcinoma.

A Phase II, open-label, single-arm, two-stage, multicenter study to evaluate the efficacy and safety of Lipotecan® monotherapy in patients with advanced hepatocellular carcinoma (HCC) and had failed sorafenib treatment due to sorafenib intolerance or radiographic progressive disease (PD).

Eligible patients received 40 mg/m2 of Lipotecan®, given as a 30-minute (+3 minutes) intravenous infusion, on Days 1, 8, and 15 of a 28-day cycle for maximum 6 cycles. Inter-cycle and intra-cycle dose delays were allowed within 21 days of the scheduled date to be reduced to 35 mg/m2 and further to 30 mg/m2 if a treatment-related adverse event (TRAE) met the criteria for dose reduction.

Tumor response was assessed every 2 cycles until Cycle 6, or at the early termination according to RECIST Version 1.1 judged by site investigator. The favorable response of CR, PR or SD would be confirmed within 28-35 days. Safety evaluations were conducted on a weekly basis from the day study treatment administered throughout each cycle.

Efficacy and Safety Study of TLC388 to Advanced Hepatocellular Carcinoma

An Open-Label, Single-Arm, Two-Stage, Multi-Centre Phase II Study to Evaluate the Efficacy and Safety of TLC388 as Second-line Treatment in Subjects With Advanced Hepatocellular Carcinoma

DCR (Disease control rate), the percentage of subjects with a best response rate of complete response (CR), partial response (PR), or stable disease (SD)

Duration of disease control is defined as the time from first documented evidence of CR or PR or SD until the first documentation of PD or death due to any cause, whichever occurs first.

Time to tumor progression is defined as the time from first study drug administration until the first documentation of tumor progression.

The PFS is defined as the time from the first dose to the date of progression or death, whichever occurs first, and subjects with no evidence of progression or death at the time of study completion (the analysis cut-off date) or who are receiving any further anticancer therapy will be censored on the date of the last adequate tumor assessment.

The OS is defined as the time from the first dose to the date of death, regardless of the cause of death, and subjects who are alive at the time of study completion will be censored at the last known alive date. Subjects who commence treatment with another anticancer agent will be censored at the day before the other anticancer treatment starts.

tumor markers/biomarkers, including α-fetoprotein (AFP), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and interleukin-6 (IL-6)

evaluate at every administration and the end of treatment

Heart and Blood Diseases

Thrombosis

Embolism

Embolism and Thrombosis

Vascular Diseases

Patients will receive Lipotecan based CCRT. Lipotecan will be given as a 30-minute (±3 minutes) iv infusion qw for 6 weeks at the predefined dose level for each cohort. A total of 6 doses of Lipotecan will be administered to each patient in conjunction with RT at 3.5 Gy per fraction for 16 fractions. During CCRT period, Lipotecan should be given within 2 hours prior to the start of RT, and the Lipotecan and RT should be delivered on the same day, unless any conditions fulfils with the dose interruption standards. Radiotherapy treatment, at the allocated dose level, is only permitted if the normal tissue dose constrain criteria are maintained

Lipotecan based concurrent chemoradiotherapy

Carl Brown, PhD

This is a phase I/II dose-escalation study of lipotecan based concurrent chemoradiotherapy in hepatocellular carcinoma with portal vein tumor thrombosis.

Protocol number: TLCTLC388A1008

Primary objective:

To evaluate the safety and tolerability, including maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), of Lipotecan based concurrent chemoradiotherapy (CCRT) in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) unsuitable for local treatment.

Secondary Objective:

The secondary objective is to explore the efficacy of Lipotecan based CCRT in patients with HCC and PVTT and the effect on quality of life.

Lipotecan Based Concurrent Chemoradiotherapy in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis

A Phase I/II, Dose-escalation Study of Lipotecan Based Concurrent Chemoradiotherapy in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis

To determine maximum tolerated dose for Lipotecan based CCRT in HCC patients with portal vein tumor thrombosis

To evaluate the best objective response rate of portal vein tumor thrombosis

To evaluate the conversion rate (CR rate) of PVTT

To evaluate the best overall response rate of overall disease

To evaluate DCR of PVTT, liver tumors (target lesions), and overall disease

To evaluate the TTP of overall disease after the start of concomitant Lipotecan based CCRT

To evaluate the PFS of overall disease after the start of concomitant Lipotecan based CCRT

To evaluate the OS after the start of concomitant Lipotecan based CCRT

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Study of Intravenous Lipotecan® (TLC388 HCl for Injection) in Patients With Advanced Solid Tumors	NCT00747474	Advanced Solid ...	Lipotecan	18 Years -	Taiwan Liposome Company
Efficacy and Safety Study of TLC388 to Advanced Hepatocellular Carcinoma	NCT02267213	Hepatocellular ...	Lipotecan	20 Years -	Taiwan Liposome Company
Lipotecan Based Concurrent Chemoradiotherapy in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis	NCT03035006	HepatoCellular ... Portal Vein Tum...	Lipotecan	18 Years -	Taiwan Liposome Company
Efficacy and Safety Study of TLC388 to Advanced Hepatocellular Carcinoma	NCT02267213	Hepatocellular ...	Lipotecan	20 Years -	Taiwan Liposome Company
Lipotecan Based Concurrent Chemoradiotherapy in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis	NCT03035006	HepatoCellular ... Portal Vein Tum...	Lipotecan	18 Years -	Taiwan Liposome Company

Spots Global Cancer Trial Database for lipotecan

Every month we try and update this database with for lipotecan cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lipotecan

Every month we try and update this database with for lipotecan cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lipotecan cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.