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
Overview
- Phase
- Phase 1
- Intervention
- Retreatment Rhenium Liposome
- Conditions
- Glioma
- Sponsor
- Plus Therapeutics
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Overall Survival
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •At least 18 years of age at time of screening.
- •Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB.
- •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.
- •At least 90 days from prior dose of 186RNL at time of screening.
- •Patients who receive treatment with antiepileptic medications must have a two-week history of stable dose of antiepileptic without seizures prior to dosing.
- •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.
- •A volume of enhancing tumor which falls within the treatment field volume being evaluated in the respective cohort (see 4.1 Design).
- •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.
- •Life expectancy of at least 2 months
- •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)
Exclusion Criteria
- •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.
- •The subject has contraindications to CNS Magnetic Resonance Imaging (MRI).
- •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.
- •The subject is pregnant or breast-feeding.
- •The subject has serious intercurrent illness, as determined by the treating physician, which would compromise either patient safety include:
- •Uncontrolled hypertension (two or more blood pressure readings performed at screening of \> 150 mmHg systolic or \> 100 mmHg diastolic) despite optimal treatment
- •non-healing wound, ulcer, or bone fracture
- •clinically significant cardiac arrhythmias affecting cardiac function
- •untreated hypothyroidism
- •uncontrolled systemic infection
Arms & Interventions
Retreatment with Rhenium Liposome
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.
Intervention: Retreatment Rhenium Liposome
Outcomes
Primary Outcomes
Overall Survival
Time Frame: 6 Months
To assess overall survival following 186RNL in patients with bevacizumab naïve recurrent glioblastoma following treatment with a second administration of 186RNL.
Assessment of safety and tolerability of a second dose of 186RNL by CED as part of standard of care >30 days following first dose.
Time Frame: > 30 days
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.
Secondary Outcomes
- Dose Distribution(3 days)
- Overall Response Rate(90 days)
- Progression-free survival(6 Months)