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)
Summary
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.
Detailed description
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.
Arms & interventions
- DrugRhenium Liposome Treatment
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.
Outcome measures
Primary
Phase 1: Maximum Tolerated Dose
Evaluation of any toxicity associated with research treatment per Common Toxicity Criteria for Adverse Events.
Time frame: 90 days
Phase 2: Overall Survival
To assess overall survival (OS) following 186RNL administration by convection enhanced delivery (CED) in patients with recurrent glioma.
Time frame: 12 Months
Secondary
Phase 1: Dose Distribution
Time frame: Up to 7 days
Phase 1: Response rate
Time frame: 8 weeks followed by standard of care
Phase 1: Survival
Time frame: 6 months
Phase 1: Safety of single dose of treatment
Time frame: Up to 3 years
Phase 2: Safety and tolerability of 186RNL
Time frame: Up to 3 years
Phase 2: Objective response rate (ORR)
Time frame: Up to 3 years.
Phase 2: Progression free survival at 6 months (PFS-6)
Time frame: Up to 6 months
Phase 2: Progression free survival (PFS) from the initiation of study to first documented progression
Time frame: Up to 3 years.
Phase 2: Quality of Life
Time frame: Up to 3 years
Eligibility criteria
Study locations (3)
Northshore University Hospital
Manhasset, New York, 11030
UT Southwestern Medical Center
Dallas, Texas, 75390
The Cancer Therapy and Research Center at UTHSCSA
San Antonio, Texas, 78229
References
- Wu C, Hormuth DA 2nd, Christenson CD, Woodall RT, Abdelmalik MRA, Phillips WT, Hughes TJR, Brenner AJ, Yankeelov TE. Image-guided patient-specific optimization of catheter placement for convection-enhanced nanoparticle delivery in recurrent glioblastoma. Comput Biol Med. 2024 Sep;179:108889. doi: 10.1016/j.compbiomed.2024.108889. Epub 2024 Jul 19.(PubMed)