A Phase 1 interventional study of TLD-1 and Caelyx in Advanced Solid Tumors, sponsored by Swiss Group for Clinical Cancer Research. Terminated at 5 sites in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-02.
Sponsored by Swiss Group for Clinical Cancer Research · Phase 1, Interventional, and Treatment
TLD-1 is a novel liposomal formulation of doxorubicin (PEG surface) that compared favorably to conventional liposomal formulations of doxorubicin including Caelyx® in preclinical in vivo models. Particle features including size, charge distribution, lipid composition and drug release add up to a considerably altered particle behavior compared to Caelyx®, potentially explaining the lack of hand-foot-syndrome in respective animal models. Preclinical evaluation confirmed TLD-1 to be a promising new and innovative formulation of doxorubicin with promising activity and good tolerability.
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 adverse events profile, pharmacokinetics and preliminary efficacy.
Swiss Group for Clinical Cancer Research is the lead sponsor of 106 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Key inclusion criteria for dose escalation part:
Key inclusion criteria for comparative PK part:
Patients with either histologically or cytologically confirmed advanced or recurrent breast or ovarian cancer of all histologies
Key exclusion criteria for dose escalation and comparative PK part:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Duration of treatment * 1 cycle: 21 days * 1 cycle: 28 days (only comparative PK part, in cycle 1 or 2) * until progression or occurrence of unacceptable toxicity or withdrawal, but * maximum 9 cycles for patients previously not treated with anthracyclines * maximum 6 cycles for patients previously treated with anthracyclines. * Dose: i.v., according to DL on day 1 of each cycle or tentative MTD
Drug: TLD-1
Duration of treatment * 1 cycle: 28 days * Caelyx is given only in one cycle (cycle 1 or 2) * Dose: i.v., 40mg/m2
Drug: Caelyx
TLD-1 is a new liposomal formulation of the anthracycline doxorubicin.
Also known as: Talidox
Caelyx is a liposomal formulation of the anthracycline doxorubicin
Dose-limiting toxicity (DLT)
Time frame: at 3 weeks
Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: volume of distribution [Vd]
Time frame: 2 months
Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: Area under curve [AUC]
Time frame: 2 months
Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: Area under curve [Cmax]
Time frame: 2 months
Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: Terminal half life [t½]
Time frame: 2 months
Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: Clearance (CL)
Time frame: 2 months
Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: Ratio of unencapsulated to encapsulated drug over time for Caelyx and TLD-1
Time frame: 2 months
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
Ran from Nov 2018 to primary completion in Sep 2023, 58 months.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Nov 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Liposomal doxorubicin
Swiss Group for Clinical Cancer Research →