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A Study of Berubicin in Adult Subjects With Recurrent Glioblastoma Multiforme

Phase 2
Active, not recruiting
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
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Lomustine (CCNU, CeeNU®, or Gleostine®) capsulesLomustineLomustine (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.
BerubicinBerubicinBerubicin 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
NameTimeMethod
Overall SurvivalThrough 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
NameTimeMethod
Overall Response RateThrough 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 tmaxThrough study completion an average of 4 years.

Time from each dose to reach the maximum plasma concentration

Plasma Pharmacokinetics RacThrough study completion an average of 4 years.

The accumulation ratio calculated as AUC0-tau (3rd dose) / AUC0-tau (1st dose)

Event Free SurvivalThrough 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-tauThrough 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 CLThrough study completion an average of 4 years.

apparent total body clearance

Plasma Pharmacokinetics CmaxThrough 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 VzThrough study completion an average of 4 years.

apparent volume of distribution

Progression Free SurvivalThrough 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-lastThrough 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 t1/2Through 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 CssThrough 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 BerubicinFrom 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.

Trial Locations

Locations (48)

Baylor Research Institute

🇺🇸

Dallas, Texas, United States

Southern California Permanente Medical Group

🇺🇸

Los Angeles, California, United States

Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

Hospital Universitari Germans Trias i Pujol

🇪🇸

Badalona, Spain

Hospital Duran i Reynals

🇪🇸

L'Hospitalet De Llobregat, Spain

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

University of Texas Health Science Center at Houston

🇺🇸

Houston, Texas, United States

Swedish Medical Center

🇺🇸

Seattle, Washington, United States

Piedmont Healthcare

🇺🇸

Atlanta, Georgia, United States

Hospital Ramón y Cajal

🇪🇸

Madrid, Spain

HCA Healthcare Research Institute

🇺🇸

Englewood, Colorado, United States

Atlantic Healthcare

🇺🇸

Summit, New Jersey, United States

UMass (ACC) - Hollings Cancer Center (HCC)

🇺🇸

Worcester, Massachusetts, United States

University of Arkansas

🇺🇸

Little Rock, Arkansas, United States

Rutgers University

🇺🇸

Piscataway, New Jersey, United States

Institut de Recherche en Cancerologie de Montpellier

🇫🇷

Montpellier, France

Servizio Sanitario Regionale Emilia-Romagna - Azienda USL di Bologna - Ospedale Bellaria

🇮🇹

Bologna, Italy

Hackensack Meridian Health

🇺🇸

Hackensack, New Jersey, United States

Hopital Pierre Wertheimer

🇫🇷

Lyon, France

Institut de Cancerologie Gustave-Roussy

🇫🇷

Villejuif, France

Istituto Clinico Humanitas

🇮🇹

Milan, Italy

Saint John's Cancer Institute at Providence Saint John's Health Center

🇺🇸

Santa Monica, California, United States

University of California Irvine

🇺🇸

Orange, California, United States

Mayo Clinic Florida

🇺🇸

Jacksonville, Florida, United States

Baptist MD Anderson Cancer Center

🇺🇸

Jacksonville, Florida, United States

Rush University Cancer Center

🇺🇸

Chicago, Illinois, United States

Ohio State University

🇺🇸

Columbus, Ohio, United States

Roswell Park Cancer Center

🇺🇸

Buffalo, New York, United States

Hopital de La Timone

🇫🇷

Marseille, France

Hopital Pitie-Salpetriere

🇫🇷

Paris, France

Institut de Cancerologie de l'Ouest

🇫🇷

Saint-Herblain, France

nstitut Universitaire du Cancer de Toulouse-

🇫🇷

Toulouse, France

Hospital Regional Universitario de Malaga Carlos Haya

🇪🇸

Málaga, Spain

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

University Hospital Zurich

🇨🇭

Zürich, Switzerland

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

University of Califonia San Diego Moores Cancer Center

🇺🇸

San Diego, California, United States

University of California San Francisco

🇺🇸

San Francisco, California, United States

Baptist Miami

🇺🇸

Miami, Florida, United States

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

Tulane Cancer Center Clinic

🇺🇸

New Orleans, Louisiana, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

Duke University School of Medicine

🇺🇸

Durham, North Carolina, United States

Providence Health

🇺🇸

Portland, Oregon, United States

Texas Oncology PA

🇺🇸

Austin, Texas, United States

Huntsman Cancer Center

🇺🇸

Salt Lake City, Utah, United States

University of Wisconsin Hospital and Clinics

🇺🇸

Madison, Wisconsin, United States

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