Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioma

Glioblastoma

Brain Neoplasms

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

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).

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

Melissa Moore, PhD

Norman LaFrance, MD (CMO)

Omar Raslan

Toral Patel, MD

Sharon Ji

Jeffrey Weinberg, MD

Epp Goodwin

Andrew J Brenner, M.D., Ph.D.

John R Floyd, M.D.

William T Phillips, M.D.

Andrew J Brenner, PhD

This is a multi-center, sequential cohort, open-label, volume and dose escalation study of the safety, tolerability, and distribution of 186RNL given by convection enhanced delivery to patients with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment. The study uses a modified Fibonacci dose escalation, followed by an expansion at the maximum tolerated dose (MTD) to determine efficacy. The starting absorbed dose is 1mCi in a volume of 0.660mL.

The Phase I portion of the clinical study evaluates a single dose of 186RNL (radionuclide clinical study drug) administered through a convection enhanced delivery catheter (CED catheter) in participants with recurrent Glioma (GBM). The clinical study treatment consists of a single administered dose of 186RNL per participant. The clinical study will include the evaluation of multiple separate dose levels (dose escalation). Three to six participants may be treated at each dose. The maximum number of participants to be enrolled in the study is approximately 21. The clinical study treatment will be administered, following CED placement, by the clinical study physician. Participants will be followed for up to 36 months after the clinical study drug is administered.

The Phase II portion of the clinical study is a multicenter, 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). The maximum number of participants to be enrolled in the Phase II study is approximately 34. The clinical study treatment will be administered, following CED placement, by the clinical study physician. Participants will be followed for up to 36 months after the clinical study drug is administered.

The U.S. Food and Drug Administration (FDA) has not approved 186RNL for this specific disease.

Phase 1:

• Single arm, prospective study utilizing a modified Fibonacci dose escalation scheme.

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).

Maximum Tolerated Dose, Safety, and Efficacy of Rhenium Nanoliposomes in Recurrent Glioma (ReSPECT)

A Dual Phase 1/2, Investigator Initiated Study to Determine the Maximum Tolerated Dose, Safety, and Efficacy of 186Rhenium Nanoliposomes (186RNL) in Recurrent Glioma (CTRC# 12-02)

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.

SPECT imaging of the radioactive materials spread across the tumor and surrounding brain

Evaluation of overall response rate by RANO criteria

Disease specific progression free survival

Evaluation of any toxicity associated with research treatment as determined by the most recent version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

To assess the safety and tolerability of 186RNL by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 criteria. Safety and tolerability will be defined by the percent of participants experiencing ≥ Grade 3 AE/SAE.

To determine the objective response rate (ORR) from the date of complete or partial response or Serious Treatment-Emergent Adverse Events (Safety and Tolerability)

To determine progression free survival at 6 months (PFS-6) as measured from the initiation of study treatment until the date of first documented progression by modified RANO criteria (recognizing the potential of pseudo progression significantly complicating the use of the RANO criteria) or date of death from any cause.

To determine progression free survival (PFS) as measured from the initiation of study treatment until the date of first documented progression by modified RANO criteria (recognizing the potential of pseudo progression significantly complicating the use of the RANO criteria) where progression is defined as \>25% in the sum of products of the perpendicular diameters of CE lesions, evidence of new lesion(s), or date of death from any cause, whichever comes first.

Evaluate assessing quality of life using a Quality-of-Life Questionnaire (developed in collaboration with FDA, Investigators and established glioblastoma patient advocacy groups)

National Cancer Institute (NCI)

Plus Therapeutics

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.

Retreatment Rhenium Liposome

Marc Hedrick, MD

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.

This Phase I clinical study evaluates a single dose of 186RNL (radionuclide clinical study drug) administered through a convection enhanced delivery catheter (CED catheter) in participants who have already received a prior treatment of 186RNL.

The clinical study treatment consists of a single administered dose of 186RNL per participant. The proposed dose is up to 8.8 mL as a single administration with an administered dose of 22.3 mCi.

An estimated number of participants to be enrolled in the study is approximately 40.

The clinical study treatment will be administered, following CED placement, by the clinical study physician.

Post-treatment evaluations will be done at Days 3, 7, 14, 28, and every subsequent 28-day interval thereafter until disease progression is confirmed and all treatment related toxicities are resolved. The minimum assessment period for toxicities is 12 weeks.

The U.S. Food and Drug Administration (FDA) has not approved 186RNL for this specific disease.

Safety & Efficacy/Tolerability of Rhenium-186 NanoLiposomes (186RNL) for Patients Who Received a Prior 186RNL 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

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.

To assess the dose distribution of a second dose of 186RNL by CED.

To determine the overall response rate by Radiographic Assessment in Neuro-Oncology (RANO) criteria following 186RNL treatment.

To determine disease specific progression-free survival after 186RNL treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Maximum Tolerated Dose, Safety, and Efficacy of Rhenium Nanoliposomes in Recurrent Glioma (ReSPECT)	NCT01906385	Glioma	Rhenium Liposom...	18 Years -	Plus Therapeutics
Safety & Efficacy/Tolerability of Rhenium-186 NanoLiposomes (186RNL) for Patients Who Received a Prior 186RNL Treatment	NCT05460507	Glioma	Retreatment Rhe...	18 Years -	Plus Therapeutics

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