Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ThermoDox · 4 trials · 3 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. |
| 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. |
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 being studied for the treatment of hepatocellular carcinoma and liver tumors. It is administered in combination with radiofrequency ablation or focused ultrasound to deliver targeted chemotherapy. ThermoDox is not yet approved and remains in clinical development.
ThermoDox is being developed by Imunon, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol IMNN. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with liver cancer.
ThermoDox is in Phase 3 clinical development for hepatocellular carcinoma. Two Phase 3 trials have been completed, along with two Phase 1 trials. The drug remains investigational and has not received FDA approval.
ThermoDox has been studied in four completed clinical trials. NCT00617981 and NCT02112656 are Phase 3 trials in hepatocellular carcinoma, while NCT00441376 and NCT02181075 are Phase 1 trials in liver tumors. All trials have been completed.
ThermoDox is a heat-activated liposomal formulation of doxorubicin. When combined with radiofrequency ablation or focused ultrasound, the heat triggers release of the chemotherapy drug directly at the tumor site, potentially increasing local drug concentration while reducing systemic exposure.
ThermoDox is not the same as standard doxorubicin. It is a liposomal formulation that encapsulates doxorubicin and releases it when heated. This targeted delivery approach is designed to concentrate the chemotherapy effect at the tumor while potentially limiting damage to healthy tissue.