TLD-1, a Novel Liposomal Doxorubicin, in Patients With Advanced Solid Tumors
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03387917|
Recruitment Status : Recruiting
First Posted : January 2, 2018
Last Update Posted : November 14, 2018
|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumors||Drug: TLD-1||Phase 1|
Despite impressive progress in the fields of surgical and immunological cancer therapies, most late-stage cancer treatments still heavily depend on conventional chemotherapeutics, which are often effective but also toxic, resulting in severe adverse effects limiting the dose and duration of therapy. Consequently, there remains a high unmet medical need for new innovative systemic treatments with an improved risk-benefit-profile.
Doxorubicin is a potent anthracycline used as a systemic treatment against several solid tumor including breast, ovarian and bladder cancer, small cell lung cancer and various types of sarcoma. However, Doxorubicin use is often limited due to hematological and non-hematological toxicity including cumulative cardiotoxicity with myocardial damage.
Cardiotoxicity has been substantially mitigated through the introduction of liposomal formulations such as Myocet and Caelyx/Doxil. Both products are associated with substantially lower rates of cardiac dysfunction during or post-treatment. Whereas Myocet's clinical use remains limited due to the intricate "bedside" reconstitution process, Caelyx has been associated with a high incidence of Palmar-Plantar Erythrodysesthesia (PPE) (also called hand-foot-syndrome), likely due to its long plasma half-life.
The development of TLD-1 (Talidox) aimed at combining the cardio-preserving properties of the liposomal delivery system with shorter blood circulation time in order to reduce the risk of PPE. Even though the pathophysiology of PPE is not yet fully understood, studies analyzing the correlation of dose and pharmacokinetic parameters with PLD toxic effects revealed that the severity of PPE correlated significantly with plasma half-life (t1/2).
Given its performance in preclinical trials, TLD-1 bears the potential for an improved benefit/risk profile compared to established liposomal doxorubicin formulations including Caelyx.
This first-in-human phase-I trial will evaluate the safety and will establish the maximal tolerated dose (MTD) and recommended phase II dose of TLD-1, and characterize specific dose limiting toxicities (DLT) of TLD-1. Moreover, the trial shall yield information on tolerability, adverse events profile, pharmacokinetics and preliminary efficacy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||The trial uses an accelerated titration design (ATD) up to the occurrence of the first DLT, followed by a modified continual reassessment method (mCRM) for dose escalation|
|Masking:||None (Open Label)|
|Official Title:||TLD-1, a Novel Liposomal Doxorubicin, in Patients With Advanced Solid Tumors: A Multicenter Open-label Single-arm Phase I Trial|
|Actual Study Start Date :||November 12, 2018|
|Estimated Primary Completion Date :||March 2020|
|Estimated Study Completion Date :||September 2020|
Duration of treatment
TLD-1 is a new liposomal formulation of the anthracycline doxorubicin.
Other Name: Talidox
- Dose-limiting toxicity (DLT) [ Time Frame: at 3 weeks ]
- Adverse Events (AEs) [ Time Frame: at 7 months ]
- Objective tumor response (OR) [ Time Frame: at 7 months ]
- Time to treatment failure (TTF) [ Time Frame: at 7 months ]
- Population pharmacokinetics (PK) of TLD-1: clearance (CL) [ Time Frame: at 2 months ]
- Population pharmacokinetics (PK) of TLD-1: volume of distribution (Vd) [ Time Frame: at 2 months ]
- Population pharmacokinetics: Area Under the Curve [AUC] [ Time Frame: at 2 months ]
- Population pharmacokinetics: Maximum Plasma Concentration [Cmax] [ Time Frame: at 2 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03387917
|Contact: Katrin Eckhardt, PhD||+41 31 389 91 firstname.lastname@example.org|
|Basel, Switzerland, 4031|
|Contact: Andreas Wicki, MD +41 61 265 50 74 email@example.com|
|Principal Investigator: Andreas Wicki, MD|
|Istituto Oncologico della Svizzera Italiana||Recruiting|
|Bellinzona, Switzerland, 6500|
|Contact: Anastasios Stathis, MD +41 91 811 89 31 firstname.lastname@example.org|
|Principal Investigator: Anastasios Stathis, MD|
|Bern, Switzerland, CH-3010|
|Contact: Manuela Rabaglio, MD +41 31 632 43 70 email@example.com|
|Principal Investigator: Manuela Rabaglio, MD|
|Chur, Switzerland, 7000|
|Contact: Sara Bastian, MD +41 81 256 68 84 firstname.lastname@example.org|
|Principal Investigator: Sara Bastian, MD|
|Kantonsspital St. Gallen||Recruiting|
|St. Gallen, Switzerland, 9007|
|Contact: Markus Joerger, MD +41 71 494 11 11 email@example.com|
|Principal Investigator: Markus Joerger, MD|
|Study Director:||Markus Joerger, MD||Cantonal Hospital of St. Gallen|
|Study Director:||Anastasios Stathis, MD||IOSI, Ospedale San Giovanni|