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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
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.
Northshore University Hospital
Manhasset, New York, United States
RECRUITINGUT Southwestern Medical Center
Dallas, Texas, United States
RECRUITINGThe Cancer Therapy and Research Center at UTHSCSA
San Antonio, Texas, United States
RECRUITINGPhase 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
Phase 1: Dose Distribution
SPECT imaging of the radioactive materials spread across the tumor and surrounding brain
Time frame: Up to 7 days
Phase 1: Response rate
Evaluation of overall response rate by RANO criteria
Time frame: 8 weeks followed by standard of care
Phase 1: Survival
Disease specific progression free survival
Time frame: 6 months
Phase 1: Safety of single dose of treatment
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).
Time frame: Up to 3 years
Phase 2: Safety and tolerability of 186RNL
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.
Time frame: Up to 3 years
Phase 2: Objective response rate (ORR)
To determine the objective response rate (ORR) from the date of complete or partial response or Serious Treatment-Emergent Adverse Events (Safety and Tolerability)
Time frame: Up to 3 years.
Phase 2: Progression free survival at 6 months (PFS-6)
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.
Time frame: Up to 6 months
Phase 2: Progression free survival (PFS) from the initiation of study to first documented progression
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.
Time frame: Up to 3 years.
Phase 2: Quality of Life
Evaluate assessing quality of life using a Quality-of-Life Questionnaire (developed in collaboration with FDA, Investigators and established glioblastoma patient advocacy groups)
Time frame: Up to 3 years
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