A Study of Berubicin in Adult Subjects With Recurrent Glioblastoma Multiforme
- Conditions
- Glioblastoma Multiforme, Adult
- Interventions
- Registration Number
- NCT04762069
- Lead Sponsor
- CNS Pharmaceuticals, Inc.
- Brief Summary
This is an open-label, multicenter, randomized, parallel, 2-arm, efficacy and safety study. Patients with GBM after failure of standard first line therapy will be randomized in a 2:1 ratio to receive berubicin or lomustine for the evaluation of OS. Additional endpoints will include response and progression outcomes evaluated by a blinded central reviewer for each patient according to RANO criteria.
A pre-planned, non-binding futility analysis will be performed after approximately 30 to 50% of all planned patients have completed the primary endpoint at 6 months. This review will include additional evaluation of safety as well as secondary efficacy endpoints. Enrollment will not be paused during this interim analysis.
- Detailed Description
Berubicin is one of the first anthracyclines that crosses the blood brain barrier and overcomes drug resistance (i.e. it is not a substrate for multi-drug resistant/breast cancer resistant transporters). A Phase 1 clinical trial of berubicin in patients with primary CNS malignancies demonstrated a durable response (one subject alive 13+ years) as well as stable disease in heavily pretreated patients. Therefore, this phase 2 study is designed to further evaluate Berubicin's activity in patients with rGBM after treatment with standard of care.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 210
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lomustine (CCNU, CeeNU®, or Gleostine®) capsules Lomustine Lomustine (CCNU, CeeNU®, or Gleostine®) capsules will be administered at the institutionally-approved dose and regimen or per the full prescribing information/summary of product characteristics. Berubicin Berubicin Berubicin intravenously infused will be administered at a dose of 7.1 mg/m2 as free base as a 2 hour intravenous (IV) infusion once daily for 3 consecutive days followed by 18 days off study drug (each cycle = 21 days) Each treatment cycle is 21 days. Subjects will be allowed to continue on treatment at the discretion of the Investigator if there is no evidence of disease progression and the subject is not experiencing unacceptable toxicity as well as if both the subject and Investigator agree that further therapy is in the subject's best interest.
- Primary Outcome Measures
Name Time Method Overall Survival Through study completion an average of 4 years. To assess the effect of berubicin compared with lomustine on overall survival (OS) in adult patients with GBM that has recurred or progressed after standard initial therapy
- Secondary Outcome Measures
Name Time Method Overall Response Rate Through study completion an average of 4 years. To assess the effect of berubicin on overall response rates (ORR) in adult patients with GBM after failure of standard first line therapy
Plasma Pharmacokinetics tmax Through study completion an average of 4 years. Time from each dose to reach the maximum plasma concentration
Plasma Pharmacokinetics Rac Through study completion an average of 4 years. The accumulation ratio calculated as AUC0-tau (3rd dose) / AUC0-tau (1st dose)
Event Free Survival Through study completion an average of 4 years. To assess the effect of berubicin on event free survival (EFS) defined as the length of time from the initiation of study drug administration to disease progression, death, or discontinuation of treatment for any reason (eg, toxicity, intolerance, disease-related conditions, or failure to respond)
Plasma Pharmacokinetics AUC0-tau Through study completion an average of 4 years. Area under the plasma concentration-time curve from time 0 to Tau, where Tau is the dosing interval, calculated by the linear up/ linear down trapezoidal method
Plasma Pharmacokinetics CL Through study completion an average of 4 years. apparent total body clearance
Plasma Pharmacokinetics Cmax Through study completion an average of 4 years. Maximum plasma concentration of Berubicin
Plasma Pharmacokinetics AUC0-∞ Through study completion an average of 4 years. Area under the plasma concentration-time curve from time 0 to infinite time, calculated as the sum of AUC0-last and Clast/λz, where Clast is the last observed quantifiable concentration
Plasma Pharmacokinetics Vz Through study completion an average of 4 years. apparent volume of distribution
Progression Free Survival Through study completion an average of 4 years. To assess the effect of berubicin on progression free survival per Response Assessment in Neuro-Oncology (RANO) criteria in patients with GBM after failure of standard first line therapy
Plasma Pharmacokinetics AUC0-last Through study completion an average of 4 years. Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration calculated by the linear up/log linear down trapezoidal method
Plasma Pharmacokinetics t1/2 Through study completion an average of 4 years. elimination half-life associated with the terminal slope (λz) of the log-linear drug concentration-time curve, calculated as ln(2)/λz
Plasma Pharmacokinetics Css Through study completion an average of 4 years. Average concentration, calculated as the geometric mean of concentrations over the 72-hour dosing interval
Safety of the Recommended Phase 2 Dose of Berubicin From signing of informed consent until until 28 days after the last dose of berubicin and 42 days after the last dose of lomustine, or until the patient receives any additional therapy for their disease (whichever comes first). To assess the safety of the recommended Phase 2 dose of berubicin by the incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0.
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
Trial Locations
- Locations (48)
University of Arkansas
🇺🇸Little Rock, Arkansas, United States
Southern California Permanente Medical Group
🇺🇸Los Angeles, California, United States
University of California Irvine
🇺🇸Orange, California, United States
University of Califonia San Diego Moores Cancer Center
🇺🇸San Diego, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Saint John's Cancer Institute at Providence Saint John's Health Center
🇺🇸Santa Monica, California, United States
HCA Healthcare Research Institute
🇺🇸Englewood, Colorado, United States
Baptist MD Anderson Cancer Center
🇺🇸Jacksonville, Florida, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Baptist Miami
🇺🇸Miami, Florida, United States
Scroll for more (38 remaining)University of Arkansas🇺🇸Little Rock, Arkansas, United States