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

Sponsor:	Taiwan Liposome Company
Information provided by (Responsible Party):	Taiwan Liposome Company
ClinicalTrials.gov Identifier:	NCT00747474

Purpose

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

Condition	Intervention	Phase
Advanced Solid Tumors	Drug: Lipotecan	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Taiwan Liposome Company:

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) of Lipotecan [ Time Frame: First treatment to toxicity up to 42 days ] [ Designated as safety issue: Yes ]
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 determined 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 [ Time Frame: start of treatment to 30 days after the last dose ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of S,S-TLC388 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of Topotecan [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U1 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Maximum Observed Dose-normalized Plasma Concentration (Cmax) of TLC-U2 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1h, 1h30m, 2h, 4h, 8h ] [ Designated as safety issue: No ]
Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,R-TLC388 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h ] [ Designated as safety issue: No ]
Time to Reach Maximum Observed Plasma Concentration (Tmax) of S,S-TLC388 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Topotecan [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U1 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Time to Reach Maximum Observed Plasma Concentration (Tmax) of TLC-U2 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,R-TLC388 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of S,S-TLC388 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of Topotecan [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U1 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of TLC-U2 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Plasma Decay Half-Life (t1/2) of S,R-TLC388 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Plasma Decay Half-Life (t1/2) of S,S-TLC388 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Plasma Decay Half-Life (t1/2) of Topotecan [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Plasma Decay Half-Life (t1/2) of TLC-U1 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]
Plasma Decay Half-Life (t1/2) of TLC-U2 [ Time Frame: 0, 15m, 29m, 33m, 40m, 50m, 1 h, 1h 30m, 2h, 4h, 8h post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Complete or Partial Response Rate by Lipotecan® Treatment [ Time Frame: every 2 cycles until progression disease ] [ Designated as safety issue: No ]
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.
Stable Disease Response Rate by Lipotecan® Treatment [ Time Frame: every 2 cycles until progression disease ] [ Designated as safety issue: No ]

Enrollment:	54
Study Start Date:	September 2008
Study Completion Date:	December 2011
Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Intervention Details:

Lipotecan IV day 1, 8, 15

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00747474

Locations

United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Massachusetts
Bidmc, Dfci, Mgh
Boston, Massachusetts, United States, 02215
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461
Taiwan
National Taiwan University Hospital
Taipei, Taiwan

Sponsors and Collaborators

Taiwan Liposome Company

Investigators

Study Director:

Min-Hsiung Kao

Taiwan Liposome Company, Ltd.

More Information

No publications provided

Responsible Party:	Taiwan Liposome Company
ClinicalTrials.gov Identifier:	NCT00747474 History of Changes
Other Study ID Numbers:	TLC388-101
Study First Received:	September 3, 2008
Results First Received:	January 5, 2012
Last Updated:	January 5, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on February 09, 2012