Approval Probability
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Adjusted LOA
ML Risk
Also known as ThermoDox® (LTLD), Lyso-Thermosensitive Liposomal Doxorubicin (LTLD), Lyso-Thermosensitive Liposomal Doxorubicin, Liposomal doxorubicin, Doxorubicin
ThermoDox · 5 trials · 4 indications
Overall survival is defined as the time (in months) from the date of randomization to the death from any cause or the end of the study.
Analytical chemistry (High Performance Liquid Chromatography) for total doxorubicin (including both released and unreleased forms) was performed on section of intratumoral biopsy samples in Good Clinical Practice Laboratory, using a validated assay. Doxorubicin concentration was evaluated in biopsy samples both post-LTLD and post-LTLD+FUS. Tumour samples were not analysed same day and were frozen at -80\^oC for subsequent analysis. Required to evaluate the primary endpoint.
To satisfy the primary endpoint, a demonstrable two-fold increase in\*, or value exceeding 10μg/g of, the concentration of intra-tumoural doxorubicin at the treated tumour site following FUS-induced mild hyperthermia, was required in at least 50% of evaluable participants. \* As per the a priori protocol design, in Part II the biopsy prior to FUS-induced mild hyperthermia is not performed and therefore the average value for all evaluable tumours receiving intervention in Part I is used as a comparison for the two-fold increase from pre-FUS to post-FUS biopsy.
| Arm | Type | Description |
|---|---|---|
| ThermoDox 50 mg/m2 | EXPERIMENTAL | ThermoDox plus standardized RFA using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm |
| Dummy infusion | PLACEBO_COMPARATOR | standardized RFA alone using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm |
| ThermoDox + RFA | EXPERIMENTAL | ThermoDox 50 mg/m2 start infusion over 30 minutes about 15 minutes before radiofrequency ablation begins. |
| Sham + RFA | SHAM_COMPARATOR | Sham infusion over 30 minutes about 15 minutes before radiofrequency ablation begins. |
| Part I | EXPERIMENTAL | All participants in Part I received: Pre-LTLD Biopsy of Target Liver Tumour ThermoDox® (LTLD) Post-LTLD Biopsy of Target Liver Tumour Focused Ultrasound of Target Liver Tumour Thermometry of Target Tumour Post-LTLD+FUS (Post-FUS) Biopsy of Target Liver Tumour Part I of the study was designed to identify optimal focused ultrasound (FUS) exposure parameters for a range of tumour locations within the liver, using real-time thermometry data from an implanted thermometry device (a thermistor or thermocouple). Plasma and biopsy samples of the target liver tumour were taken pre-LTLD, post-LTLD and post-LTLD+FUS. |
| Part II | EXPERIMENTAL | All participants in Part II received: ThermoDox® (LTLD) Focused Ultrasound of Target Liver Tumour Post-LTLD Biopsy of Target Liver Tumour Following a minimum of 5 Part I cases, and subject to Trial Management Group approval, Part II of the study was opened to run in parallel to Part I. Part II did not require implantation of a thermometry device, and instead used predictions from Part I data to set the FUS parameters. Targeted drug delivery in Part II thus proceeded completely non-invasively, and this part of the study was designed to more closely reflect how the therapy might be implemented in routine clinical practice. Plasma samples were taken pre-LTLD, post-LTLD and post-LTLD+FUS. Biopsy samples of the target liver tumour were taken only post-LTLD+FUS. |
| Thermodox in combination with hyperthermia | EXPERIMENTAL | Single arm study |
| Name | Type | Description |
|---|---|---|
| ThermoDox | DRUG | Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion |
| Dummy infusion | DRUG | Sodium Chloride 0.9% or 5% Dextrose (D5W), Single 30 minute intravenous infusion |
| 5% Dextrose Solution | DRUG | Single 30 minute intravenous infusion |
| ThermoDox® (LTLD) | DRUG | ThermoDox® (LTLD) infusion at a dose of 50mg/m2 whilst under general anaesthetic during intervention (Day 1) |
| Focused Ultrasound of Target Liver Tumour | DEVICE | Whilst the ThermoDox® was circulating in the blood stream, the JC200 Therapeutic Ultrasound device was used to induce mild hyperthermia in a single (region of) a target liver tumour. |
| Pre-LTLD Biopsy of Target Liver Tumour | DIAGNOSTIC_TEST | - |
| Post-LTLD Biopsy of Target Liver Tumour | DIAGNOSTIC_TEST | - |
| Post-LTLD+FUS (Post-FUS) Biopsy of Target Liver Tumour | DIAGNOSTIC_TEST | - |
| Thermometry of Target Tumour | DEVICE | A clinically approved thermistor or thermocouple was placed in the target liver tumour for real-time thermometry. |
| ThermoDox in combination with Microwave Hyperthermia (heat) | DRUG | ThermoDox is a 30 minute intravenous infusion followed by hyperthermia within 60 minutes of infusion completion. Hyperthermia is a therapy used to heat tumors for 60 minutes. Using heat energy, the tumor is heated to a certain temperature. The heat can damage cancer cells at levels that are usually safe for normal cells and can be used to attack cancer in four major ways: 1) heat damages or weakens the cells of the tumor; 2) heat increase blood flow through the weakened tumor; 3) increased blood flow raises oxygen levels in tumors; and 4) when the body senses fever it can stimulate the nature immune system. All patients will receive up to six ThermoDox/hyperthermia treatments at 21-day intervals. |
Inclusion Criteria: 1. Male or female ≥ 18 years of age. 2. Diagnosed with a single HCC lesion ≥ 3.0 cm but ≤ 7.0 cm in maximum diameter based on diagnosis at screening. * Subjects meeting the American Association for the Study of Liver Disease (AASLD) criteria may be randomized without a biops...
ThermoDox is an investigational small molecule oncology drug developed by Imunon, Inc. (ticker IMNN). It is being studied in breast cancer, hepatocellular carcinoma, and liver tumors. ThermoDox is designed to be used in combination with heat-based techniques such as microwave hyperthermia or radiofrequency ablation. It remains in clinical development and is not approved.
ThermoDox is being studied for hepatocellular carcinoma, liver tumors, and breast cancer that has recurred at the chest wall. Clinical trials have combined ThermoDox with radiofrequency ablation for hepatocellular carcinoma and with hyperthermia for breast cancer recurrence. These uses are investigational and have not been approved by regulators.
ThermoDox is developed by Imunon, Inc., which trades on the Nasdaq under the ticker IMNN. Imunon is the sponsor of the clinical program evaluating ThermoDox in liver and breast cancer indications.
ThermoDox is in clinical development and is investigational. Its program includes Phase 1 and Phase 3 studies, all of which are completed, with no trials currently active. The Phase 3 trials evaluated ThermoDox with radiofrequency ablation in hepatocellular carcinoma, while Phase 1 work covered liver tumors and breast cancer.
ThermoDox has been studied in completed trials including NCT00617981 and NCT02112656, both Phase 3 studies of ThermoDox with radiofrequency ablation in hepatocellular carcinoma, and NCT02181075, a Phase 1 study in liver tumors. NCT00826085 was a Phase 1/2 study of ThermoDox with hyperthermia in breast cancer recurrence at the chest wall.