Rhenium-186 NanoLiposome for Leptomeningeal Metastasis

(ReSPECT-LM Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, 186RNL (Rhenium-186 NanoLiposome), for individuals with leptomeningeal metastases, where cancer spreads to the brain and spinal cord lining. The study aims to determine a safe dose of 186RNL by gradually increasing the amount given to participants until the optimal level is identified. Each participant will receive a single dose directly into the brain via a small tube. Individuals with confirmed leptomeningeal metastases who can manage daily life with some limitations might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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 there any evidence suggesting that 186RNL is likely to be safe for humans?

Research has shown that Rhenium-186 NanoLiposome (186RNL) is generally safe for humans. In one study, four adult patients received a single dose of 186RNL through a tube delivering medicine directly into the brain. None of these patients experienced severe side effects that would prevent the treatment from being used at higher doses.

This early evidence suggests that 186RNL might be safe for further testing. However, since this study is in an early phase, it primarily focuses on understanding safety and dosage. Researchers will closely monitor participants to ensure their well-being throughout the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for leptomeningeal metastasis, which often involve systemic chemotherapy or radiation, 186RNL is a targeted treatment that utilizes Rhenium-186, a radioactive isotope, encapsulated in nanoliposomes. This innovative delivery method allows for direct administration into the cerebrospinal fluid, potentially increasing the concentration of the active agent at the site of the metastasis while minimizing systemic exposure and side effects. Researchers are excited about 186RNL because its unique delivery system could enhance treatment effectiveness and provide a new avenue for managing a condition that is notoriously difficult to treat with existing options.

What evidence suggests that 186RNL might be an effective treatment for Leptomeningeal Metastasis?

Research has shown that 186RNL, the investigational treatment in this trial, may help treat conditions like leptomeningeal metastasis. In studies with 17 patients, 5 experienced some tumor shrinkage, and 8 had their disease remain stable for over 3 months, resulting in a 76% benefit rate. Another study found that a single dose of 186RNL was well tolerated by adult patients. 186RNL delivers targeted radiation to cancer cells and allows doctors to track its progress through imaging. These findings suggest that 186RNL could help control tumor growth in patients with leptomeningeal metastasis. ^{2 3 4 5 6}

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

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]

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 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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12342460/

CTSI-06 PHASE 1 DOSE ESCALATION OF RHENIUM ... Radiographic response data available for 17 patients showed 5 partial responses and 8 stable disease through day 112 (76% benefit rate). Additionally, a ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/64/supplement_1/P978

Preliminary Clinical Data in The Phase 1/2a Dose Escalation ... A single treatment with 186 RNL delivered by an intraventricular catheter (Ommaya reservoir) in 4 adult patients is well tolerated, without dose limiting ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/PS14-01/753296/Abstract-PS14-01-Rhenium-186Re-obisbemeda-rhenium

Abstract PS14-01: Rhenium (186Re) obisbemeda (rhenium ... Rhenium (186Re) Obisbemeda (186RNL) provides the combination of effective therapeutic beta radiation, simultaneous gamma decay for imaging ...

4. ir.plustherapeutics.com ir.plustherapeutics.com/static-files/415202a9-4f0f-4478-a604-ea0a183c34b7

Rhenium (186Re) Obisbemeda (Rhenium Nanoliposome, ... Patients were treated with 186RNL over the first 5 cohorts, as described. Ages ranged (at time of treatment) between 29-76 years old. 35% were ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07098806

Study Details | NCT07098806 | Multiple Dose ... This is an open-label, multicenter, Phase 1 study to determine the safety and efficacy of multiple doses at defined intervals of rhenium (186Re) obisbemeda ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11296769/

OCTS-11 PHASE 1 DOSE ESCALATION OF RHENIUM ... Rhenium (186Re) Obisbemeda (186RNL) provides the combination of effective therapeutic beta radiation, simultaneous gamma-decay for imaging, and ...