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Also known as Rhenium-186 Nanoliposome, Retreatment Rhenium Liposome, Rhenium Liposome Treatment
186RNL · 5 trials · 4 indications
Determine the maximum tolerated dose (MTD) of 186RNL administered by convection-enhanced delivery (CED) in subjects with supratentorial recurrent, refractory, or progressive pediatric ependymoma or HGG.
Determine the best overall response rate (ORR) by Radiographic Assessment in Neuro-Oncology (RANO) criteria following 186RNL administration in subjects with supratentorial recurrent, refractory, or progressive pediatric ependymoma.
Determine progression-free survival at 12 months (PFS12) in subjects with supratentorial recurrent, refractory, or progressive pediatric HGG.
Evaluation of any toxicity associated with research treatment per Common Criteria for Adverse Events.
SPECT imaging of the radioactive materials spread in the Cerebrospinal Fluid.
Evaluation of any toxicity associated with research treatment as determined by National Cancer Institute (NCI) common Terminology Criteria for adverse events (CTCAE).
Safety and tolerability assessed by number of participants with treatment-related toxicities and/or adverse events as assessed by CTCAE v4.0 with 4-week evaluation periods for toxicity and disease assessment until disease progression is suspected.
To assess overall survival following 186RNL in patients with bevacizumab naïve recurrent glioblastoma following treatment with a second administration of 186RNL.
Safety will be evaluated by the incidence of AEs and SAEs graded according CTCAE version 5.0.
Maximum Tolerated Dose (MTD) will be evaluated by testing increasing doses with 3 to 6 participants in each cohort. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants.
Evaluation of any toxicity associated with research treatment per Common Toxicity Criteria for Adverse Events.
To assess overall survival (OS) following 186RNL administration by convection enhanced delivery (CED) in patients with recurrent glioma.
| Arm | Type | Description |
|---|---|---|
| Phase 1a - Cohort A | EXPERIMENTAL | Up to six subjects will be enrolled in Cohort A. Tumor size will be limited to a maximum diameter of (less than or equal to) ≤2 cm and a maximum volume of (less than or equal to) ≤4.2 mL. Up to two CED catheters will be utilized in Cohort A at the discretion and consensus of the PI, neurosurgeon, and/or study team. The concentration of 186RNL infusate in Cohort A is 0.5 mCi/mL, with a corresponding estimated absorbed dose of \~87.5Gy. |
| Phase 1a - Cohort B | EXPERIMENTAL | Up to six subjects will be enrolled in Cohort B. Tumor size will be limited to a maximum diameter of 3.5 cm in the longest axis and a maximum volume of 22.4 mL. Up to 5 total catheters may be used for Cohort B at the discretion and consensus of the PI, neurosurgeon, and/or study team to ensure total tumor volume coverage. The concentration of 186RNL infusate in Cohort B is 1.0 mCi/mL with a corresponding estimated absorbed dose of \~176Gy (\~2x Cohort A). |
| Phase 1b | EXPERIMENTAL | Phase 1b continued dosing escalation will be defined following review of the safety data from Phase 1a. |
| Phase 2 | EXPERIMENTAL | The Phase 2 expansion study will utilize the maximum tolerable dose (MFD) determined from the Phase 1 dose escalation study. If no maximal tolerable dose is found, tumors may be treated up to an estimated total absorbed dose of 176 Gy. Varying concentrations of 186RNL infusate (0.5-2.5 mCi/mL) may be used to achieve this maximum tolerable dose while maintaining total tumor volume coverage. Phase 2a will enroll an additional 12 patients with a diagnosis of recurrent, refractory, or progressive ependymoma and an additional 20 patients with a diagnosis of recurrent, refractory, or progressive HGG. |
| Experimental: Multiple Doses | EXPERIMENTAL | 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 (rhenium-186 nanoliposome, 186RNL) administered via intraventricular catheter for any primary solid tumor cancer with leptomeningeal metastases to identify an MTD/MFD for a given dose, interval duration, and number of doses. |
| Retreatment with Rhenium Liposome | EXPERIMENTAL | 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. |
| Dose Escalation | EXPERIMENTAL | 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. |
| 186Rhenium Liposome Treatment | EXPERIMENTAL | Arm Phase I: Experimental: Dose Escalation for Cohorts 1-8 Each participant will receive a single 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 as shown below: COHORT ACTIVITY Cohort 1 (1.0 mCi) Cohort 2 (2.0 mCi) Cohort 3 (4.0 mCi) Cohort 4 (8.0 mCi) Cohort 5 (13.4 mCi) Cohort 6 (22.3 mCi) Cohort 7 (31.2 mCi) Cohort 8 (41.5 mCi) Phase 2: Single arm, prospective study utilizing a non-DLT dose obtained from the dose escalation portion of IND 116117, NIH-NCI Grant (22.3 mCi (total 186RNL activity) at a concentration of 2.5 mCi/mL and 8.8 mL total volume). |
| Name | Type | Description |
|---|---|---|
| Rhenium-186 Nanoliposome | DRUG | Rhenium (186Re) Obisbemeda (Rhenium-186 NanoLiposome, 186RNL), BMEDA-chelated-186rhenium encapsulated within liposomes, allows the 186Re to be directly delivered to the site of the tumor through CED and maintain localization at the site of infusion. |
| 186RNL | DRUG | Multiple Doses of 186RNL |
| Retreatment Rhenium Liposome | DRUG | At the time of stereotactic biopsy a catheter will be placed within the tumor using stereotactic guidance. Once the patient has adequately recovered from the procedure as determined by the neurosurgeon, 186RNL will be infused through the CED catheter at the predetermined dose. Spectroscopic imaging will then be obtained at predefined time points to visualize the distribution of the 186RNL as well as calculated the actual dose retained within the tumor. Patients will be monitored longitudinally for evidence of toxicity and response by MRI. |
| Rhenium Liposome Treatment | DRUG | At the time of stereotactic biopsy a catheter will be placed within the tumor using stereotactic guidance. Once the patient has adequately recovered from the procedure as determined by the neurosurgeon, 186RNL will be infused through the CED catheter at the predetermined dose. Spectroscopic imaging will then be obtained at predefined time points to visualize the distribution of the 186RNL as well as calculated the actual dose retained within the tumor. Patients will be monitored longitudinally for evidence of toxicity and response by MRI. |
Inclusion Criteria: 1. 6 years to 21 years\* of age. 2. Lesion number and size: 1. Phase 1a/b only: A single lesion (less than or equal to) ≤3.5 cm (longest axis) and volume of (less than or equal to) ≤22.4 mL as the largest tumor (subsequent to individual Cohort lesion size requirements). 2...