TLD-1, a Novel Liposomal Doxorubicin, in Patients With Advanced Solid Tumors

NCT03387917 | Terminated Phase 1 DMC

• 1 other identifier: SAKK 65/16
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Advanced Solid Tumors

Keywords

Advanced Solid Tumors; doxorubicin; TLD-1; phase I; Talidox; Liposomal

Outcome Measures

Primary Outcomes (7)

• Dose-limiting toxicity (DLT)

  at 3 weeks

• Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: volume of distribution [Vd]

  2 months

• Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: Area under curve [AUC]

  2 months

• Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: Area under curve [Cmax]

  2 months

• Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: Terminal half life [t½]

  2 months

• Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: Clearance (CL)

  2 months

• Descriptive pharmacokinetics (PK) of TLD-1 vs Caelyx: Ratio of unencapsulated to encapsulated drug over time for Caelyx and TLD-1

  2 months

Secondary Outcomes (7)

• Adverse Events (AEs)

  at 7 months

• Objective tumor response (OR)

  at 7 months

• Time to treatment failure (TTF)

  at 7 months

• Population pharmacokinetics (PK) of TLD-1: clearance (CL)

  at 2 months

• Population pharmacokinetics (PK) of TLD-1: volume of distribution (Vd)

  at 2 months

Study Arms (2)

TLD-1

EXPERIMENTAL

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

Caelyx (only for comparative PK part)

EXPERIMENTAL

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

Interventions

TLD-1 DRUG

TLD-1 is a new liposomal formulation of the anthracycline doxorubicin.

Also known as: Talidox

TLD-1

Caelyx DRUG

Caelyx is a liposomal formulation of the anthracycline doxorubicin

Caelyx (only for comparative PK part)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Final protocol until amendment 2: Patients with either histologically or cytologically confirmed advanced or recurrent solid tumor who failed standard therapy or for whom no effective standard therapy is available
• From Amendment 3 on: Patients with histologically or cytologically confirmed advanced malignant tumors of the breast, ovary, uterine or sarcoma who failed standard therapy or for whom no effective standard therapy is available.
• Patients may have received up to 3 prior lines of palliative systemic chemotherapy
• Patients with brain metastases must have undergone definitive treatment (surgery and/or radiation) at least 1 month prior to starting study drug and be documented as having stable disease by imaging and are on stable doses of steroids for at least 2 weeks.
• Adequate bone marrow, renal and hepatic function
• Patients with either histologically or cytologically confirmed advanced or recurrent breast or ovarian cancer of all histologies
• Histologically-confirmed ovarian, fallopian tube or primary peritoneal cancer (collectively referred to herein as 'ovarian cancer') that is either platinum-resistant (disease progression within 6 months of the last receipt of platinum-based chemotherapy) or refractory (lack of response or disease progression while receiving the most recent platinum-based therapy).
• Patients with ovarian cancer may have received up to 3 lines of prior cytotoxic chemotherapy, but maximum 1 of them in the platinumresistant/ refractory setting. Confirmed high-grade serous, endometrioid, or carcinosarcoma histotypes are permitted.
• Patients with advanced or recurrent breast cancer may have received up to 2 prior lines of palliative cytotoxic chemotherapy.
• Patients with brain metastases must have undergone definitive treatment (surgery and/or radiation) at least 1 month prior to starting study drug and be documented as having stable disease by imaging and be on stable doses of steroids for at least 2 weeks.
• Adequate bone marrow, renal and hepatic function

You may not qualify if:

• Significant cardiac disease or abnormality
• Patients who have received prior anthracyclines at a cumulative dose that exceeds 250mg/m2 for non-liposomal doxorubicin, 300mg/m2 for liposomal doxorubicin or 400mg/m2 for epirubicin and/or are refractory (during 3 months) to anthracyclines or have experienced allergic reactions or severe toxicity (grade 3 or 4) under anthracyclines
• Prior systemic chemotherapy/treatment for adjuvant/metastatic disease, radiotherapy, immunotherapy, or investigational agents within 28 days 5 half- life periods of previous therapy before registration.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (5)

Istituto Oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Related Publications (3)

• Klose M, Colombo I, Gobat K, Koster KL, Haefliger S, Rabaglio M, Bastian S, Schwitter M, Zurrer-Hardi U, Eckhardt K, Hayoz S, Halbherr S, Sessa C, Michelet R, Mc Laughlin AM, Hess D, Stathis A, Kloft C, Joerger M. TLD-1, a Novel Liposomal Doxorubicin, in Patients with Solid Tumors: Comparative Pharmacokinetics and Final Results of a Multicenter Phase 1 Study (SAKK 65/16). Clin Pharmacokinet. 2025 Nov 18. doi: 10.1007/s40262-025-01588-z. Online ahead of print.

  PMID: 41252081 DERIVED

• Mc Laughlin AM, Hess D, Michelet R, Colombo I, Haefliger S, Bastian S, Rabaglio M, Schwitter M, Fischer S, Eckhardt K, Hayoz S, Kopp C, Klose M, Sessa C, Stathis A, Halbherr S, Huisinga W, Joerger M, Kloft C. Population pharmacokinetics of TLD-1, a novel liposomal doxorubicin, in a phase I trial. Cancer Chemother Pharmacol. 2024 Sep;94(3):349-360. doi: 10.1007/s00280-024-04679-z. Epub 2024 Jun 15.

  PMID: 38878207 DERIVED

• Colombo I, Koster KL, Holer L, Haefliger S, Rabaglio M, Bastian S, Schwitter M, Eckhardt K, Hayoz S, Mc Laughlin AM, Kloft C, Klose M, Halbherr S, Baumgartner C, Sessa C, Stathis A, Hess D, Joerger M. TLD-1, a novel liposomal doxorubicin, in patients with advanced solid tumors: Dose escalation and expansion part of a multicenter open-label phase I trial (SAKK 65/16). Eur J Cancer. 2024 Apr;201:113588. doi: 10.1016/j.ejca.2024.113588. Epub 2024 Feb 2.

  PMID: 38377773 DERIVED

MeSH Terms

Interventions

liposomal doxorubicin

Study Officials

• Dagmar Hess, MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

• Anastasios Stathis, MD

  IOSI, Ospedale San Giovanni

  STUDY DIRECTOR

• Markus Jörger, Prof

  Cantonal Hospital of St. Gallen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 part and randomized cross-over design for the comparative PK part

Study Record Dates

• First Submitted: November 21, 2017
• First Posted: January 2, 2018
• Study Start: November 12, 2018
• Primary Completion: September 22, 2023
• Study Completion: December 22, 2023
• Last Updated: December 2, 2024

Record last verified: 2024-11

Locations

CH (5)