Thermodox + MR-HIFU for Cancer

Recruiting in Palo Alto (17 mi)

Overseen by AeRang Kim, MD, PhD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Children's National Research Institute

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses a heat-activated drug and a non-invasive heating technology to treat patients with hard-to-treat or recurring tumors. The drug is activated by heat, and then higher heat is used to destroy the tumor cells.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications. However, you cannot receive any other anti-cancer therapy (chemotherapy, biological therapy, radiation therapy) while participating in this trial.

What data supports the idea that Thermodox + MR-HIFU for Cancer is an effective treatment?

The available research shows that Thermodox combined with MR-HIFU is effective in increasing the concentration of the cancer-fighting drug doxorubicin directly in tumors. In a study with rabbits, this combination resulted in significantly higher levels of doxorubicin in tumors compared to using the drug alone. Another study in rats demonstrated that the treatment effectively released the drug at the target site when heated, showing a good correlation between the drug uptake and the temperature increase. These findings suggest that Thermodox + MR-HIFU can deliver more of the drug to the tumor, potentially making it more effective than traditional methods. ^{1 2 3 4 5}

What safety data is available for Thermodox + MR-HIFU treatment?

The safety data for Thermodox (Lyso-thermosensitive Liposomal Doxorubicin, LTLD) combined with MR-HIFU includes several studies. A Phase I feasibility study in breast cancer patients aims to increase local doxorubicin levels without increasing systemic toxicity. Another Phase I study focused on determining the maximum tolerated dose and dose-limiting toxicity of LTLD during radiofrequency ablation for hepatic malignancies. These studies suggest that LTLD can be safely administered with hyperthermia techniques like MR-HIFU, with a focus on optimizing local drug delivery while minimizing systemic side effects. ^{1 3 5 6 7}

Is the drug Lyso-thermosensitive Liposomal Doxorubicin a promising treatment for cancer?

Yes, Lyso-thermosensitive Liposomal Doxorubicin (ThermoDox) is a promising treatment for cancer. It uses heat to release the drug directly into tumors, increasing its concentration where it's needed most. This targeted approach can improve the drug's effectiveness while reducing side effects. Studies have shown that longer heating times can significantly increase the amount of drug delivered to the tumor, enhancing its therapeutic effect. ^{4 5 8 9 10}

Research Team

AeRang Kim, MD, PhD

Principal Investigator

Children's National Research Institute

Eligibility Criteria

This trial is for individuals aged 12 or older with certain types of solid tumors that have not responded to standard treatments. Participants must be in a stable health condition, with specific requirements for blood cell counts and organ function. They should have at least one tumor accessible to HIFU treatment and no other curative options available.

Inclusion Criteria

I have recovered from side effects of all my previous cancer treatments.

My kidney function is normal or near normal.

I can do most activities but need help with some.

Exclusion Criteria

I have a tumor in my skull.

I cannot stay still for long periods during treatments.

You are currently taking other medications for cancer treatment.

Treatment Details

Interventions

• Lyso-thermosensitive Liposomal Doxorubicin (Chemotherapy)
• Magnetic Resonance-Guided High Intensity Focused Ultrasound (Procedure)

Trial Overview The study tests the combination of LTLD (a type of chemotherapy) with MR-HIFU, which uses magnetic resonance imaging to guide focused ultrasound for heating and destroying cancer cells. The goal is to see if this approach is effective in treating relapsed or refractory solid tumors.

Participant Groups

Group I: All Patients Experimental Treatment 2 Interventions

LTLD 50 mg/m2 will be administered intravenously over 30 minutes on day 1 of every 21-day cycle. MR-HIFU hyperthermia will follow infusion (+/- 30 minutes) for one hour to a target area with a target temperature of 40-45°C followed by ablation therapy (\>55°C). The HIFU hyperthermia regimen will have a duration of at least 60 minutes and will then be followed by ablation therapy. Patients may receive up to a total of 6 cycles. Subsequent treatment cycles may treat alternative target lesions. Disease status will be evaluated using standard imaging techniques (CT/MR) post each cycle.

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Michelle Riley-Brown

Children's National Research Institute

Chief Executive Officer since 2023

MHA from Washington University School of Medicine in St. Louis, Bachelor's degree from Tulane University

Catherine Bollard

Children's National Research Institute

Chief Medical Officer

MBChB, MD

Findings from Research

The maximum tolerated dose (MTD) of lyso-thermosensitive liposomal doxorubicin (LTLD) was determined to be 50 mg/m², with dose-limiting toxicity observed at 60 mg/m², indicating a safe dosage for use in combination with radiofrequency ablation.

LTLD was associated with manageable side effects, specifically reversible neutropenia and leukopenia, suggesting it can be safely administered alongside RF ablation for treating liver tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies. Wood, BJ., Poon, RT., Locklin, JK., et al.[2023]

References

1. India pubmed.ncbi.nlm.nih.gov

Thermosensitive liposomal doxorubicin plus radiofrequency ablation increased tumor destruction and improved survival in patients with medium and large hepatocellular carcinoma: A randomized, double-blinded, dummy-controlled clinical trial in a single center. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Image-guided drug delivery with magnetic resonance guided high intensity focused ultrasound and temperature sensitive liposomes in a rabbit Vx2 tumor model. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Phase I feasibility study of Magnetic Resonance guided High Intensity Focused Ultrasound-induced hyperthermia, Lyso-Thermosensitive Liposomal Doxorubicin and cyclophosphamide in de novo stage IV breast cancer patients: study protocol of the i-GO study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Hyperthermia-mediated doxorubicin release from thermosensitive liposomes using MR-HIFU: therapeutic effect in rabbit Vx2 tumours. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging of high intensity focused ultrasound mediated drug delivery from temperature-sensitive liposomes: an in vivo proof-of-concept study. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Drug development of lyso-thermosensitive liposomal doxorubicin: Combining hyperthermia and thermosensitive drug delivery. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Phase I study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Longer heating duration increases localized doxorubicin deposition and therapeutic index in Vx2 tumors using MR-HIFU mild hyperthermia and thermosensitive liposomal doxorubicin. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Magnetic resonance guided high-intensity focused ultrasound mediated hyperthermia improves the intratumoral distribution of temperature-sensitive liposomal doxorubicin. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device. [2021]