Clinical trial NCT00747474: Phase I Study of Intravenous Lipotecan® (TLC388 HCl for Injection) in Patients With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Taiwan Liposome Company
Sponsor class: INDUSTRY
First posted: 2008-09-05
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Lipotecan
timeFrame: First treatment to toxicity up to 42 days
measure: Number of Participants With Adverse Events
timeFrame: an average of 6 months
measure: Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,R-TLC388
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,S-TLC388
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Maximum Observed Dose-normalized Plasma Concentration (Cmax) of Topotecan
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U1
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U2
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1h, 1h30m, 2h, 4h, 8h
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,R-TLC388
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,S-TLC388
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Topotecan
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U1
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U2
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,R-TLC388
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,S-TLC388
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Topotecan
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U1
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U2
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Plasma Decay Half-Life (t1/2) of S,R-TLC388
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Plasma Decay Half-Life (t1/2) of S,S-TLC388
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Plasma Decay Half-Life (t1/2) of Topotecan
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Plasma Decay Half-Life (t1/2) of TLC-U1
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
measure: Plasma Decay Half-Life (t1/2) of TLC-U2
timeFrame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose
Secondary outcomes:
measure: Anti-tumor Activity
timeFrame: From start of treatment assessed every 2 cycles up to 2.5 years
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Boston
country: United States
facility: Bidmc, Dfci, Mgh
state: Massachusetts
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Taiwan Liposome Company, Ltd.
name: Min-Hsiung Kao
role: STUDY_DIRECTOR
References: