A Study of Berubicin in Adult Subjects With Recurrent Glioblastoma Multiforme

NCT04762069 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CNS-201
• Study Type: interventional
• Target: 252
• Locations: 5 countries
• Sites: 48

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.

Conditions

Glioblastoma Multiforme, Adult

Keywords

Glioblastoma Multiforme; Glioblastoma; Brain Cancer; Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  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

  Through study completion an average of 4 years.

Secondary Outcomes (14)

• Progression Free Survival

  Through study completion an average of 4 years.

• Event Free Survival

  Through study completion an average of 4 years.

• Overall Response Rate

  Through study completion an average of 4 years.

• 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).

• Plasma Pharmacokinetics Cmax

  Through study completion an average of 4 years.

Other Outcomes (5)

• Karnofsky Performance Status

  Through study completion an average of 4 years.

• Evaluate changes in patient-reported outcomes

  Through study completion an average of 4 years.

• Explore the effect of O[6] methylguanine-DNA methyltransferase (MGMT) methylation

  Through study completion an average of 4 years.

Study Arms (2)

Berubicin

EXPERIMENTAL

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.

Drug: Berubicin

Lomustine (CCNU, CeeNU®, or Gleostine®) capsules

ACTIVE COMPARATOR

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.

Drug: Lomustine

Interventions

Lomustine DRUG

Lomustine is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. This medication is classified as an "alkylating agent.

Also known as: Lomustine Capsules, CCNU, CeeNU, Gleostine

Lomustine (CCNU, CeeNU®, or Gleostine®) capsules

Berubicin DRUG

Berubicin HCl is a novel synthetic anthracycline with a chemical structure similar to doxorubicin HCl, a cytotoxic anthracycline topoisomerase II inhibitor isolated from cultures of Streptomyces peucetius var. caesius.

Also known as: Berubicin Hydrochloride

Berubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Written informed consent from the patient or their legally authorized representative (LAR) prior to any study-related procedure, and willing and able to comply with the protocol and aware of the investigational nature of this study.
• At least 18 years of age.
• KPS score of ≥ 60
• A confirmed GBM diagnosis must be based on local review of tumor tissue from the initial biopsy, surgery, or re-resection. A formal pathology report confirming GBM is acceptable. It is not a requirement for slides to be sent to a central reviewer.
• Recurrent or progressive GBM as evaluated by central review applying RANO criteria on contrast MRI scans of the Baseline/Screening MRI scan obtained up to six weeks prior to C1D1 and a historical scan taken before the Baseline/Screening scan that meets at least 1 of the following criteria:
• In the case of measurable disease, progression will be documented by ≥ 25% increase in the sum of the perpendicular diameter products (SPDPs) of the measurable contrast-enhancing (target) lesions or any new measurable lesions.
• If the SPDPs cannot be reliably estimated due to the lesion's complex conspicuity, shape, and contrast enhancement pattern, the volume of all measurable and non-measurable lesions may be used instead, applying the same threshold (≥ 25% increase) to confirm disease progression.
• In the case of non-measurable lesions in the historical scan, any transformation into measurable lesions (≥10 mm in both maximum perpendicular diameters) in the Baseline/Screening scan will be evidence of progression.
• If there are only non-measurable (non-target) lesions in the Baseline/Screening scan, additional lesions/sites will be considered evidence of progression based on the historical scan. Patients with new cerebrospinal fluid (CSF) seeding will not be considered eligible.
• If historical scans are unavailable, a radiology report of a scan taken before the Baseline/Screening scan documenting the SPDPs from a previous scan of the enhancing disease or its volume can be used by the central reviewer to assess eligibility if it demonstrates the quality standards and acquisition guidelines required.
• Patients at first progression who are treated by re-resection or biopsy to confirm progression do not require measurable disease at their post-operative screening scan as their Baseline/Screening scan. These patients must be medically stable after the procedure as assessed by the PI and have the Baseline/Screening scan available by 7 days before starting treatment.
• The tumor is localized supratentorially with no leptomeningeal (local or distant), spinal or CSF metastases, and no ventricular invasion (explicit documentation of the disease progression that would be problematic in evaluating the efficacy of this drug).
• O\[6\] methylguanine-DNA methyltransferase (MGMT) methylation status must be available; results of routinely used methods for MGMT methylation testing (eg, methylation-specific polymerase chain reaction or quantitative polymerase chain reaction) are acceptable.
• No more than 1 prior line of treatment (eg, surgery followed by radiation with concomitant chemotherapy, followed by adjuvant chemotherapy is considered as 1 line of treatment). In addition, treatment with tumor treating fields (TTFields; Optune) is acceptable if provided as first line therapy prior to progression or recurrence of disease.
• A second debulking surgery, additional radiation or gamma knife surgery during the first line treatment or after progression, and for which the investigator does not suspect pseudoprogression is acceptable, as long as no chemotherapy or immunotherapy has been provided.

Sponsors & Collaborators

• CNS Pharmaceuticals, Inc.: lead
• Worldwide Clinical Trials: collaborator

Study Sites (48)

University of Arkansas

Little Rock, Arkansas, 72205, United States

Location

Southern California Permanente Medical Group

Los Angeles, California, 90027, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

University of Califonia San Diego Moores Cancer Center

San Diego, California, 92093, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

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

Santa Monica, California, 90404, United States

Location

HCA Healthcare Research Institute

Englewood, Colorado, 80113, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Baptist Miami

Miami, Florida, 33176, United States

Location

Piedmont Healthcare

Atlanta, Georgia, 30309, United States

Location

Rush University Cancer Center

Chicago, Illinois, 60612, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Tulane Cancer Center Clinic

New Orleans, Louisiana, 70112, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

UMass (ACC) - Hollings Cancer Center (HCC)

Worcester, Massachusetts, 01655, United States

Location

Mayo Clinic

Rochester, Minnesota, 550905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

Location

Rutgers University

Piscataway, New Jersey, 08854, United States

Location

Atlantic Healthcare

Summit, New Jersey, 07901, United States

Location

Roswell Park Cancer Center

Buffalo, New York, 14263, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27710, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Providence Health

Portland, Oregon, 97225, United States

Location

Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Texas Oncology PA

Austin, Texas, 78758, United States

Location

Baylor Research Institute

Dallas, Texas, 75246, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77027, United States

Location

Huntsman Cancer Center

Salt Lake City, Utah, 84112, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53705, United States

Location

Hopital Pierre Wertheimer

Lyon, France

Location

Hopital de La Timone

Marseille, France

Location

Institut de Recherche en Cancerologie de Montpellier

Montpellier, France

Location

Hopital Pitie-Salpetriere

Paris, France

Location

Institut de Cancerologie de l'Ouest

Saint-Herblain, France

Location

nstitut Universitaire du Cancer de Toulouse-

Toulouse, France

Location

Institut de Cancerologie Gustave-Roussy

Villejuif, France

Location

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

Bologna, Italy

Location

Istituto Clinico Humanitas

Milan, Italy

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Spain

Location

Hospital Duran i Reynals

L'Hospitalet de Llobregat, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Regional Universitario de Malaga Carlos Haya

Málaga, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

University Hospital Zurich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Lomustine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Study Officials

• Sandra Silberman, MD, PhD

  CNS Pharmaceuticals, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Response and progression outcomes are evaluated by a blinded central reviewer for each patient according to RANO criteria
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-Label Study with a Randomized Control Arm

Study Record Dates

• First Submitted: November 11, 2020
• First Posted: February 21, 2021
• Study Start: May 18, 2021
• Primary Completion: April 27, 2026
• Study Completion (Estimated): July 15, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (32); ES (6); FR (7); IT (2); CH (1)