Evaluating Rhenium-186 NanoLiposomes for Recurrent Glioma Treatment

A Single Arm Open Label Study to Determine the Safety and Efficacy/Tolerability of Rhenium-186 NanoLiposomes (186RNL) for Recurrence of Glioma in Patients Who Received a Prior Treatment With 186RNL

This study is testing a new treatment using Rhenium-186 NanoLiposomes to see if it can safely help people with recurrent glioma who have already had this type of therapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Plus Therapeutics (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (San Antonio, Texas)
• Trial ID: NCT05460507 on ClinicalTrials.gov

What this trial studies

This Phase 1 clinical study aims to assess the safety and efficacy of a single dose of Rhenium-186 NanoLiposomes (186RNL) administered via an intraventricular catheter in patients with recurrent glioma who have previously received this treatment. The study will enroll approximately 40 participants, who will undergo post-treatment evaluations at specified intervals to monitor for treatment-related toxicities and disease progression. The treatment involves a single administration of 186RNL, with a focus on understanding its tolerability and effectiveness in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with biopsy-proven recurrent glioma who have previously been treated with Rhenium-186 NanoLiposomes.

Not a fit: Patients who have not received prior treatment with Rhenium-186 NanoLiposomes or those with other types of brain tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with recurrent glioma, potentially improving their outcomes.

How similar studies have performed: While this approach is novel in the context of recurrent glioma, similar studies using radionuclide therapies have shown promise in other cancer types.

Eligibility criteria

Inclusion Criteria:

1. At least 18 years of age at time of screening.
2. Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB.
3. Patient must present with biopsy and histology proven glioma following initial treatment with 186RNL. The type and grade of glioma to follow the 2021 WHO Classification of Tumors of the Central Nervous System, allowing Grade III and IV gliomas.
4. At least 90 days from prior dose of 186RNL at time of screening.
5. Patients who receive treatment with antiepileptic medications must have a two-week history of stable dose of antiepileptic without seizures prior to dosing.
6. Patients with corticosteroid requirements to control cerebral edema must be maintained at a stable or decreasing dose for a minimum of two weeks without progression of clinical symptoms.
7. A volume of enhancing tumor which falls within the treatment field volume being evaluated in the respective cohort (see 4.1 Design).
8. ECOG performance status of 0 to 2; ECOG 3 acceptable if Principal Investigator and treating physician confirm in patient's interest in study/re-treatment.
9. Life expectancy of at least 2 months
10. Acceptable liver function: Bilirubin ≤ 1.5 times upper limit of normal and AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal (ULN)
11. Acceptable renal function: Serum creatinine ≤1.5xULN
12. Acceptable hematologic status (without hematologic support): ANC ≥1000 cells/uL, Platelet count ≥100,000/uL if no bleeding, Hemoglobin ≥7.0 g/dL. Given the absence of hematological toxicity in the ongoing recurrent glioblastoma trial (#12-02) and the need for CED catheter placement, the Investigator and Sub-investigator (neurosurgeon) placing the CED catheter may determine that it is in the patient's best interest and acceptably safe to proceed with this criteria with hematological support or, if no bleeding, Platelet count ≥75,000/uL without support, ANC 1000 cells/uL and Hemoglobin ≥7.0 g/dL
13. 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 (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.
14. Patients must have malignant glioma that has progressed on or after standard treatment (surgery, radiotherapy, and/or chemotherapy) and are planned to undergo stereotactic biopsy as per standard of care.

Exclusion Criteria:

1. The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible.
2. The subject has contraindications to CNS Magnetic Resonance Imaging (MRI).
3. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for any prior Adverse Events (CTCAE) v4.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study.
4. The subject is pregnant or breast-feeding.
5. The subject has serious intercurrent illness, as determined by the treating physician, which would compromise either patient safety include:

   1. Uncontrolled hypertension (two or more blood pressure readings performed at screening of \> 150 mmHg systolic or \> 100 mmHg diastolic) despite optimal treatment
   2. non-healing wound, ulcer, or bone fracture
   3. clinically significant cardiac arrhythmias affecting cardiac function
   4. untreated hypothyroidism
   5. uncontrolled systemic infection
   6. symptomatic congestive heart failure or unstable, untreated angina pectoris within 3 months prior study drug
   7. myocardial infarction, stroke, transient ischemic attack within 6 months
   8. known active malignancy (other than glioma) except non-melanoma skin cancer or carcinoma in-situ in the cervix
6. The subject has an inherited bleeding diathesis or coagulopathy with the risk of bleeding.
7. The subject has received any of the following prior anticancer therapy:

   1. Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy, or intra-operative radiotherapy (IORT) to the target site.
   2. Other CNS radiation therapy within 12 weeks of screening.
   3. Systemic therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (e.g., tamoxifen) within 14 days or 5 half-lives, whichever is shorter, prior first dose of study drug
   4. Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug
   5. Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug
   6. Prior CNS treatment with carmustine wafers
   7. Patients who are currently receiving any other investigational agents and/or who have received an investigational agent in the prior 28 days from screening.
   8. Patient actively enrolled in an ongoing investigational drug or device trial excluding follow-up only in a previously trial.
8. Multifocal progression or involvement of the leptomeninges.
9. Psychiatric illness/social situations that would limit compliance with the study requirements.
10. Infratentorial disease unless Investigator and neurosurgeon agree it is treated disease.

Where this trial is running

San Antonio, Texas

• The Cancer Therapy and Research Center at UTHSCSA — San Antonio, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Andrew J Brenner, PhD — The Cancer Therapy and Research Center at UTHSCSA
• Study coordinator: Rachael Hershey

Conditions Glioma; Brain Tumor; Radiotherapy; Glioblastoma; Recurrent Glioblastoma; Rhenium; Rhenium Nanoliposome; Brain Cancer