ThermoDox (lyso-thermosensitive liposomal doxorubicin) / Imunon - LARVOL DELTA

Thermosensitive liposomal doxorubicin combined with hyperthermic intravesical chemotherapy for treatment of non-muscle invasive bladder cancer (AUA 2025) - "Applying hyperthermia to intravesical mitomycin C (MMC) enhances drug penetration; however, drug deposition in the deep muscularis and serosa remains challenging. Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of liposome-encapsulated doxorubicin (DOX) that is released when exposed to mild hyperthermic temperatures (39-42°C)... Treatment with a combination of intravenous LTLD and HIVEC was feasible and well-tolerated and resulted in substantial accumulation of DOX in the bladder wall without thermal damage, offering a potentially synergistic approach that merits consideration for a clinical trial for NMIBC."

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Ultrasound-assisted efficient targeting of doxorubicin to the tumor microenvironment by lyso-thermosensitive liposomes of varying phase transition temperatures. (PubMed, Eur J Pharm Sci) - "Premature drug release is the primary hindrance to the effective function of the lyso-thermosensitive liposomes (LTSLs) of doxorubicin (Dox), known as ThermoDox® for the treatment of cancer. Among various formulations, F25 (DPPC: MSPC: DSPE-mPEG2000: HSPC, 65:10:4:25) showed the highest cellular uptake at 42℃ and significantly improved the antitumor and survival efficacy in mice bearing C26 colon carcinoma in combination with ultrasonic HT compared to F0. Collectively, results demonstrated that optimizing the rigidity of the liposomal bilayers through the combinatorial selection of PLs of different transition temperatures could improve the plasma stability of the liposome, and hence ameliorate the outcome of therapy in assistance with an effective HT approach."

Biomarker • Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Children's National Research Institute | N=14 ➔ 0 | Trial completion date: Dec 2025 ➔ Dec 2024 | Recruiting ➔ Withdrawn | Trial primary completion date: Dec 2025 ➔ Dec 2024

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Ewing Sarcoma • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor

Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice. (PubMed, Int J Mol Sci) - "In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1)...The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CASP3

A PILOT STUDY OF LYSO-THERMOSENSITIVE LIPOSOMAL DOXORUBICIN AND MAGNETIC RESONANCE-GUIDED HIGH INTENSITY FOCUSED ULTRASOUND FOR TREATMENT OF RELAPSED OR REFRACTORY SOLID TUMORS (CTOS 2023) - P2 | "N/A, trials in progress"

Clinical • Oncology • Solid Tumor

Data demonstrating the in vivo anti-tumor efficacy of thermosensitive liposome formulations of a drug combination in pre-clinical models of breast cancer. (PubMed, Data Brief) - "Our group previously developed and characterized a thermosensitive liposome formulation of the heat shock protein 90 inhibitor alvespimycin as a companion therapeutic to a thermosensitive liposome formulation equivalent in composition to ThermoDox (i.e., ThermoDXR), with the goal of increasing the therapeutic index of doxorubicin as the combination was revealed to be highly synergistic in a panel of human breast cancer cell lines including MDA-MB-231 (Dunne et al., 2019). The data presented here further describes the effect of the doxorubicin (DXR) and alvespimycin (ALV) combination in vitro and in vivo. Specifically, the combination effect in mouse breast cancer 4T1 cells and the in vivo efficacy of this heat-activated chemotherapy combination in both immunocompromised (MDA-MB-231 tumor bearing female SCID mice) and immunocompetent (4T1 tumor bearing female BALB/c mice) models of breast cancer."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

Clinical trial protocol for PanDox: a phase I study of targeted chemotherapy delivery to non-resectable primary pancreatic tumours using thermosensitive liposomal doxorubicin (ThermoDox®) and focused ultrasound. (PubMed, BMC Cancer) - P1 | "This early phase study builds on previous work targeting tumours in the liver to investigate whether enhancement of chemotherapy delivery using ultrasound-mediated hyperthermia can be translated to the stroma-dense environment of pancreatic ductal adenocarcinoma. If successful, it could herald a new approach towards managing these difficult-to-treat tumours."

Journal • P1 data • Anesthesia • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors (clinicaltrials.gov) - P1 | N=2 | Terminated | Sponsor: AeRang Kim | N=34 ➔ 2 | Recruiting ➔ Terminated; low accrual

Enrollment change • Trial termination • CNS Tumor • Ewing Sarcoma • Gastrointestinal Cancer • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Neuroblastoma • Neuroendocrine Tumor • Oncology • Osteosarcoma • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor

A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors (clinicaltrials.gov) - P2 | N=14 | Recruiting | Sponsor: Children's National Research Institute | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Ewing Sarcoma • Gastrointestinal Cancer • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor

PanDox: Targeted Doxorubicin in Pancreatic Tumours (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: University of Oxford | N=18 ➔ 0 | Trial completion date: Dec 2022 ➔ Mar 2023 | Recruiting ➔ Withdrawn | Trial primary completion date: May 2022 ➔ Mar 2023

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors (clinicaltrials.gov) - P2 | N=14 | Recruiting | Sponsor: Children's National Research Institute | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Enrollment open • Trial completion date • Trial primary completion date • Ewing Sarcoma • Gastrointestinal Cancer • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor

Heat-Activated Doxorubicin Uptake Facilitated by Laser Interstitial Thermal Therapy (SNO 2022) - "Doxorubicin was identified in 100% of mice treated with LITT following ThermoDox administration which is in contrast with groups treated with LITT and PBS, sham and ThermoDox, and sham and PBS. Here, we show that heat-activated nanoparticles are disrupted through hyperthermia followed by the release of doxorubicin only in the presence of hyperthermia, which paves way for the clinical use of ThermoDox as adjunct chemotherapy following LITT in treatment-resistant GBM treatment."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Heat-Activated Doxorubicin Uptake Facilitated by Laser Interstitial Thermal Therapy (SNO 2022) - "Doxorubicin was identified in 100% of mice treated with LITT following ThermoDox administration which is in contrast with groups treated with LITT and PBS, sham and ThermoDox, and sham and PBS. Here, we show that heat-activated nanoparticles are disrupted through hyperthermia followed by the release of doxorubicin only in the presence of hyperthermia, which paves way for the clinical use of ThermoDox as adjunct chemotherapy following LITT in treatment-resistant GBM treatment."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Accord Healthcare Launches Generic Doxorubicin PEGylated Liposomal Concentrate (PRNewswire) - "Accord Healthcare today announced the launch of a generic Doxorubicin pegylated liposomal 2mg/ml concentrate for solution for infusion in the UK and Europe....The product is indicated: As monotherapy for patients with metastatic breast cancer, where there is an increased cardiac risk; For treatment of advanced ovarian cancer in women who have failed a first-line platinum-based chemotherapy regimen; In combination with bortezomib for the treatment of progressive multiple myeloma in patients who have received at least one prior therapy and who have already undergone or are unsuitable for bone marrow transplant; For treatment of AIDS-related Kaposi's sarcoma (KS) in patients with low CD4 counts (<200 CD4 lymphocytes/mm³) and extensive mucocutaneous or visceral disease."

Generic launch • Breast Cancer • Gynecologic Cancers • Hematological Malignancies • Kaposi Sarcoma • Multiple Myeloma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor

Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin. (PubMed, Front Pharmacol) - "By using thermally sensitive lysolipids in its bilayer composition, ThermoDox implemented a heat-induced controlled release of DOX. Being folate-targeted, in vitro DFPML antitumoral activity is higher (IC ≈ 1 μg/ml) for folate receptor-overexpressing B16F10 murine melanoma cells, compared to MCF7 human breast adenocarcinoma cells (IC ≈ 4 μg/ml). Taken together, our results indicate that DFPML are strong candidates for folate-targeted anticancer therapies based on DOX controlled release."

Journal • Breast Cancer • Melanoma • Oncology • Solid Tumor

EURO-DIGNITY: Heat-Activated Target Therapy of Local-Regional Relapse in Breast Cancer Patients (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Celsion | N=70 ➔ 0 | Suspended ➔ Withdrawn

Enrollment change • Trial withdrawal • Breast Cancer • Oncology • Solid Tumor

A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors (clinicaltrials.gov) - P1; N=34; Recruiting; Sponsor: AeRang Kim; Trial completion date: Oct 2021 ➔ Oct 2022; Trial primary completion date: Oct 2021 ➔ Oct 2022

Clinical • Trial completion date • Trial primary completion date • Ewing Sarcoma • Gastrointestinal Cancer • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Neuroblastoma • Oncology • Osteosarcoma • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • MRI

Turning down the heat: The case for mild hyperthermia and thermosensitive liposomes. (PubMed, Nanomedicine) - "The OPTIMA trial, as it was known, evaluated their thermosensitive liposome (TSL) formulation of doxorubicin (ThermoDox®) in combination with radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). As formulation scientists working in the field, we continue to believe that heat-triggered drug delivery platforms have tremendous potential as chemotherapy. Herein, we highlight potential limitations in the design of many of the Thermodox clinical trials, and we propose that despite these setbacks, TSLs have the potential to become an effective component of cancer therapy."

Clinical • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors (clinicaltrials.gov) - P2; N=14; Not yet recruiting; Sponsor: Children's National Research Institute; Initiation date: Oct 2021 ➔ Feb 2022

Clinical • Trial initiation date • Ewing Sarcoma • Gastrointestinal Cancer • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • MRI

Celsion GmbH Announces the Publication of an Article Reviewing the History of ThermoDox Drug Development in Advanced Drug Delivery Reviews (GlobeNewswire) - "'As our recent paper in Advanced Drug Delivery Reviews points out there was much learned regarding the application of ThermoDox with heat technology. The publication of this article helps to educate clinical researchers about the compelling results in early-stage studies we have achieved in multiple oncology targets (notably bladder and brain) during our years of work with ThermoDox®, which may catalyze further investigation.'....Evaluation of ThermoDox® deployment in the rectal mucosa with endorectal heating. This preclinical study in a swine model seeks to explore the feasibility of the maximum tolerated dose of intravenous ThermoDox® administration with endorectal heating of mucosa to assess the feasibility, depth of penetration and drug levels in the acute setting."

Clinical data • Preclinical • Bladder Cancer • Breast Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Oncology • Urothelial Cancer

"$CLSN Celsion GmbH Announces the Publication of an Article Reviewing the History of ThermoDox® Drug Development in Advanced Drug Delivery Reviews https://t.co/79FJlrwITT" (@stock_titan)

Computational modeling of thermal combination therapies by magneto-ultrasonic heating to enhance drug delivery to solid tumors. (PubMed, Sci Rep) - "For the first time, inspired by magnetic resonance imaging-guidance high intensity focused ultrasound (MR-HIFU) technology, i.e., medication therapy and thermal ablation in one session, in a preclinical setting based on a developed mathematical model, the performance of doxorubicin (Dox) and its encapsulation have been investigated in this study...On the other hand, the intravascular release of ThermoDox increases the concentration of free drug by 2.6 times compared to classical chemotherapy...Therefore, it is recommended that ablation be performed after the medication therapy. Our model describes a comprehensive assessment of MR-HIFU technology, taking into account many effective details, which can be a reliable guide towards the optimal use of drug delivery systems."

Combination therapy • Journal • Oncology • Solid Tumor • MRI

Drug Development of Lyso-thermosensitive Liposomal Doxorubicin: Combining Hyperthermia and Thermosensitive Drug Delivery. (PubMed, Adv Drug Deliv Rev) - "At the target the carrier is activated by heat and releases its contents at high concentrations. We summarize the preclinical and clinical experience of LTLD including its successes and challenges in the development process."

Journal • Review • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

PanDox: Targeted Doxorubicin in Pancreatic Tumours (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: University of Oxford; Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors (clinicaltrials.gov) - P2; N=14; Not yet recruiting; Sponsor: Children's National Research Institute; Initiation date: Jun 2021 ➔ Oct 2021

Clinical • Trial initiation date • Ewing Sarcoma • Gastrointestinal Cancer • Germ Cell Tumors • Hepatocellular Cancer • Hepatology • Liver Cancer • Nephrology • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • MRI