Rhenium-186 NanoLiposomes for Brain Tumor

Overseen By Rachael Hershey

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Plus Therapeutics

Must be taking: Antiepileptics, Corticosteroids

Must not be taking: Investigational agents, Biologic agents

Disqualifiers: Uncontrolled hypertension, Cardiac arrhythmias, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, multicenter, Phase 1 study to establish the safety and efficacy/tolerability of a single dose of 186RNL by the intraventricular route (via intraventricular catheter) for recurrence glioma in patients who received a prior treatment of 186RNL.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop all current medications, but it does require a stable dose of antiepileptic medications for two weeks and a stable or decreasing dose of corticosteroids for two weeks before starting. Some prior cancer treatments must be stopped for a certain period before the trial.

What data supports the effectiveness of the treatment Rhenium-186 NanoLiposomes for brain tumors?

Research shows that Rhenium-186 liposomes, when used in a rat model for brain tumors, significantly increased survival time compared to controls, with no significant toxicity observed. This suggests that the treatment may effectively target tumors while minimizing harm to healthy tissue. ^{1 2 3 4 5}

Is Rhenium-186 NanoLiposomes safe for use in humans?

Studies on Rhenium-186 NanoLiposomes in animal models, such as rats, have shown that high doses can be administered without obvious signs of toxicity. Additionally, similar treatments with Rhenium-188 NanoLiposomes in mice did not cause significant weight changes or acute toxicity, suggesting a favorable safety profile. ^{2 3 4 5 6}

What makes Rhenium-186 NanoLiposomes unique for treating brain tumors?

Rhenium-186 NanoLiposomes are unique because they deliver high doses of radiation directly to brain tumors using a method called convection-enhanced delivery, which allows for targeted treatment with minimal toxicity. This approach differs from traditional external beam radiation, which can be limited by its side effects at high doses. ^{1 2 3 4 5}

Research Team

Andrew J Brenner, PhD

Principal Investigator

The Cancer Therapy and Research Center at UTHSCSA

Eligibility Criteria

This trial is for adults over 18 with certain high-grade brain tumors (Grade III or IV gliomas) who've already been treated with Rhenium-186 NanoLiposomes. They should be stable on medications for seizures and cerebral edema, have acceptable liver function, an ECOG performance status of 0 to 3, and a life expectancy of at least two months.

Inclusion Criteria

Life expectancy of at least 2 months

I can care for myself but may not be able to do all my normal activities.

I've been on a stable dose of my seizure medication for at least two weeks without seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of 186RNL administered via convection enhanced delivery catheter

1 day

1 visit (in-person)

Post-treatment Evaluation

Evaluations are conducted at Days 3, 7, 14, 28, and every 28 days thereafter until disease progression and resolution of toxicities

12 weeks minimum

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Rhenium-186 NanoLiposomes

Trial Overview The study tests the safety and effectiveness of giving a second dose of Rhenium-186 NanoLiposomes via an intraventricular catheter to patients whose brain tumors returned after initial treatment. It's open-label and multicenter, meaning both researchers and participants know what treatment is being given.

Participant Groups

Group I: Retreatment with Rhenium Liposome Experimental Treatment 1 Intervention

Each participant will receive a single administration of 186RNL. The proposed dose is up to 8.8 mL as a single administration with an administered dose of 22.3 mCi.

Who Is Running the Clinical Trial?

Plus Therapeutics

Lead Sponsor

Trials

3

Recruited

110+

Findings from Research

Liposomes containing a radioactive rhenium complex were successfully created, with about 45% of the complex incorporated into the liposome bilayer, indicating effective encapsulation for potential therapeutic use.

The stability of these liposomes improved with the addition of ascorbic acid, reducing radioactivity loss from 40% to 20% over 8 days, which is crucial for their application in beta-radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A lipophilic complex with 186Re/188Re incorporated in liposomes suitable for radiotherapy. Häfeli, U., Tiefenauer, LX., Schbiger, PA., et al.[2019]

Brachytherapy using rhenium-186 (186Re) liposomes delivered via convection-enhanced delivery showed promising results in a rat model of glioma, with doses up to 1850 Gy administered without significant toxicity.

Treatment with (186)Re-liposomes significantly improved median survival (126 days) compared to controls (49 days), indicating a strong potential for this method in treating primary brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma. Phillips, WT., Goins, B., Bao, A., et al.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model. [2018]

2. England pubmed.ncbi.nlm.nih.gov

A lipophilic complex with 186Re/188Re incorporated in liposomes suitable for radiotherapy. [2019]

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

Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma. [2021]

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

Liposomes loaded with a dirhenium compound and cisplatin: preparation, properties and improved in vivo anticancer activity. [2015]

5. New Zealand pubmed.ncbi.nlm.nih.gov

External beam radiotherapy synergizes ¹⁸⁸Re-liposome against human esophageal cancer xenograft and modulates ¹⁸⁸Re-liposome pharmacokinetics. [2018]

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

PEGylated liposome-encapsulated rhenium-188 radiopharmaceutical inhibits proliferation and epithelial-mesenchymal transition of human head and neck cancer cells in vivo with repeated therapy. [2020]