Rhenium-186 NanoLiposome for Leptomeningeal Metastasis

(ReSPECT-LM Trial)

Recruiting at 6 trial locations

Overseen By Brandallyn Tihinen, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Plus Therapeutics

Must not be taking: Systemic chemotherapy, Nitrosoureas

Disqualifiers: Hydrocephalus, Cardiac arrhythmias, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is an open-label Phase I clinical study that will administer a single dose of 186RNL via intraventricular catheter for treatment of Leptomeningeal Metastases (LM).

Will I have to stop taking my current medications?

The trial requires a 'washout' period (time without taking certain medications) for some drugs, especially those that affect the central nervous system or are systemic therapies. If you are on such medications, you may need to stop them for a certain period before joining the trial. It's best to discuss your specific medications with the trial team.

Is Rhenium-186 NanoLiposome safe for humans?

Rhenium-186 NanoLiposome has been studied in different forms and conditions, showing that it can be administered safely with minimal non-marrow toxicity. In some studies, higher doses led to myelosuppression (a decrease in bone marrow activity), but non-marrow side effects were minimal, indicating it is generally safe for human use. ^{1 2 3 4 5}

What makes the Rhenium-186 NanoLiposome treatment unique for leptomeningeal metastasis?

Rhenium-186 NanoLiposome is unique because it uses liposomally encapsulated radionuclides for targeted brachytherapy, allowing high doses of radiation to be delivered directly to the tumor site with minimal toxicity, unlike traditional external beam radiation which is limited by its toxicity at high doses. ^{2 3 4 5 6}

What data supports the effectiveness of the treatment Rhenium-186 NanoLiposome for Leptomeningeal Metastasis?

Research on Rhenium-186 liposomes for brain tumors showed that it can be delivered safely and effectively, significantly extending survival in animal models. Additionally, Rhenium-186 has been used in other treatments, like radioimmunotherapy, where it was safely administered with limited toxicity, suggesting its potential effectiveness in treating cancer. ^{3 4 5 7 8}

Who Is on the Research Team?

Andrew Brenner, MD, PhD

Principal Investigator

The Cancer Therapy and Research Center at UTSHSCSA

Are You a Good Fit for This Trial?

Adults with documented Leptomeningeal Metastases (LM) who understand the study and consent to participate. They must have a Karnofsky performance status of 60-100, proper kidney and liver function, acceptable blood counts, not be pregnant or breastfeeding, use effective contraception, and have no severe illnesses or recent significant cardiovascular events.

Inclusion Criteria

All women of childbearing potential must have a negative serum pregnancy test at screening. Male and female subjects must agree to use effective means of contraception with their partner from entry into the study through 6 months after the last dose

My liver function tests are within the required range.

My leptomeningeal metastases (LM) fit the study's specific type requirements.

Exclusion Criteria

I have a bleeding disorder that poses a high risk of bleeding.

I have received radiation to my brain or spinal cord, or had radiation for a tumor not in my brain.

I have a condition where fluid builds up in my brain, causing symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single 5cc dose of 186RNL administered via intraventricular catheter

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits (frequency not specified)

What Are the Treatments Tested in This Trial?

Interventions

• 186RNL

Trial Overview The trial is testing a single dose of an experimental treatment called 186RNL administered directly into the cerebrospinal fluid via a catheter for patients with LM. It's an early-phase study to see how safe it is and how well it works.

How Is the Trial Designed?

Group I: Dose Escalation Experimental Treatment 1 Intervention

Each participant will receive a single 5cc administration of 186RNL. At each dose level, a minimum of three to a maximum of six participants will be enrolled. If no dose limiting toxicity is observed in the initial three participants, then the next higher dose level cohort will open for enrollment. The dose escalation scheme will follow a modified Fibonacci dose escalation scheme.

186RNL is already approved in United States for the following indications:

Approved in United States as Rhenium (186Re) obisbemeda for:

• Leptomeningeal Metastases (LM)
• Recurrent Glioblastoma (GBM)

Who Is Running the Clinical Trial?

Plus Therapeutics

Lead Sponsor

Trials

3

Recruited

110+

Published Research Related to This Trial

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]

The new rhenium-186 hydroxyethylidene diphosphonate radiopharmaceutical effectively targets metastatic bone cancer, delivering high therapeutic radiation doses to cancerous areas while minimizing exposure to healthy bone marrow.

In a study involving five patients, this agent demonstrated a biodistribution similar to standard bone-scanning agents, suggesting it can safely treat multiple metastatic sites in bone simultaneously.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-186(Sn) HEDP for treatment of multiple metastatic foci in bone: human biodistribution and dosimetric studies. Maxon, HR., Deutsch, EA., Thomas, SR., et al.[2013]

The novel focal brachytherapy technique using lipid nanoparticles carrying rhenium-186 and rhenium-188 can effectively deliver high therapeutic doses to the lumpectomy cavity and draining lymph nodes while minimizing exposure to surrounding healthy tissue.

This method allows for targeted treatment of areas with a higher likelihood of residual tumor cells after surgery, potentially improving treatment outcomes and reducing complications associated with radiation exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postlumpectomy focal brachytherapy for simultaneous treatment of surgical cavity and draining lymph nodes. Hrycushko, BA., Li, S., Shi, C., et al.[2021]

In two Phase I trials involving 46 patients with refractory metastatic epithelial carcinoma, 186Re-labeled antibodies were found to be safely administered, with dose-limiting myelosuppression occurring at higher doses, indicating a need for careful dose management.

While non-marrow toxicity was minimal, the treatment did elicit human anti-mouse antibodies in all patients receiving the intact antibody and in 86% of those receiving the F(ab')2 fragment, suggesting an immune response that could impact treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: results of phase I trials. Breitz, HB., Weiden, PL., Vanderheyden, JL., et al.[2004]

The study involved 17 women with recurrent or persistent ovarian carcinoma, and the treatment with rhenium 186 conjugated to a monoclonal antibody showed acceptable toxicity levels, with severe side effects occurring only at the highest dose.

Out of the patients treated, four showed a decrease in tumor size, indicating that this immunoconjugate can produce objective responses in patients with minimal disease after just one dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of a rhenium 186-labeled monoclonal antibody administered intraperitoneally in ovarian carcinoma: toxicity and clinical response. Jacobs, AJ., Fer, M., Su, FM., et al.[2009]

Rhenium-186 (186Re) is effective for radioimmunotherapy, providing accurate imaging and dosimetry for both normal organs and tumors in 46 patients, with tumor dose estimates ranging from 0.4 to 18.6 rads/mCi.

While 186Re dosimetry could not be reliably predicted for individual patients, the study confirmed that 99mTc imaging can accurately predict tumor localization and provides comparable estimates for radiation absorbed doses to normal organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetry of rhenium-186-labeled monoclonal antibodies: methods, prediction from technetium-99m-labeled antibodies and results of phase I trials. Breitz, HB., Fisher, DR., Weiden, PL., et al.[2016]

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]

The novel rhenium compounds (PC1-6) demonstrated significant cytotoxicity against triple node negative breast cancer cell lines (HTB-132) in a 48-hour treatment study, indicating their potential as effective cancer treatments.

These rhenium compounds were found to be less nephrotoxic compared to cisplatin, suggesting a safer alternative for patients undergoing treatment for highly malignant breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer Properties of Novel Rhenium Pentylcarbanato Compounds against MDA-MB-468(HTB-132) Triple Node Negative Human Breast Cancer Cell Lines. Parson, C., Smith, V., Krauss, C., et al.[2020]

Citations

1. England pubmed.ncbi.nlm.nih.gov

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

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

Re-186(Sn) HEDP for treatment of multiple metastatic foci in bone: human biodistribution and dosimetric studies. [2013]

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

Postlumpectomy focal brachytherapy for simultaneous treatment of surgical cavity and draining lymph nodes. [2021]

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

Clinical experience with rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: results of phase I trials. [2004]

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

A phase I trial of a rhenium 186-labeled monoclonal antibody administered intraperitoneally in ovarian carcinoma: toxicity and clinical response. [2009]

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

Dosimetry of rhenium-186-labeled monoclonal antibodies: methods, prediction from technetium-99m-labeled antibodies and results of phase I trials. [2016]

7. England pubmed.ncbi.nlm.nih.gov

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

8. India pubmed.ncbi.nlm.nih.gov

Anticancer Properties of Novel Rhenium Pentylcarbanato Compounds against MDA-MB-468(HTB-132) Triple Node Negative Human Breast Cancer Cell Lines. [2020]