A Study of Berubicin in Adult Subjects With Recurrent Glioblastoma Multiforme

Running, not enrolling · Phase 2

Conditions studied: Glioblastoma Multiforme, Adult

In brief

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.

Key facts

Study ID

NCT04762069

Run by

CNS Pharmaceuticals, Inc.

People needed

252

Starts

2021-05-18

Expected to finish

2026-07-15

Last updated by the study team

2026-04-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may 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.
• If the scan obtained during standard of care (prior to initiation of formal clinical screening and patient enrollment) is being used as the Baseline/Screening scan and does not entirely conform to central reader quality standards and acquisition guidelines (ie, artifacts or missing sequences), this can be used for the purpose of inclusion if the central reader in discussion with the sponsor and PI agree it provides evidence based on standard clinical practices of recurrence or progression.
• 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.
• Recovery from toxicity/side effects of all prior therapy to Grade 1 or less, subject to the investigator's discretion, except for alopecia; the following time intervals from previous treatments are required to be eligible:
• 12 weeks from the completion of radiation (to reduce risk of pseudoprogression), unless progression is confirmed by biopsy
• 4 weeks from the end of any previous of chemotherapy
• 2 weeks from tumor biopsy if wound completely healed
• 4 weeks from any major surgery (maximal debulking surgery, either gross total resection or partial resection), gamma knife surgery or significant traumatic injury. Any surgery incisions or wounds must be completely healed
• A stable or decreasing dose of corticosteroids (or none) for brain edema for at least 5 days prior to baseline MRI and enrollment in the study to document disease progression such that changes in the MRI are not related to the use of corticosteroids.
• Eligible for chemotherapy based on adequate bone marrow function and organ function within 2 weeks of study treatment as defined by the following laboratory guidelines, subject to the investigator's discretion:
• Hematopoietic function: total white blood cell (WBC) count ≥3 × 103/µL, absolute neutrophil count (ANC) ≥1.5 × 10³/µL, platelet count ≥75 × 10³/µL, hemoglobin ≥10 g/dL
• Hepatic function: bilirubin ≤1.5 × × the upper limit of normal (ULN) (excluding Gilberts Syndrome, for which bilirubin must be ≤4 × ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 × ULN, and alkaline phosphatase ≤2.5 × ULN

You may not qualify if…

• Unable or not willing to comply with the protocol regulations.
• Any additional chemotherapy (including but not limited to TMZ or immunotherapy) for recurrent or progressive GBM after a first line treatment.
• Prior treatment with bevacizumab.
• Prior treatment with lomustine.
• Known to have an IDH mutation prior to enrollment
• Screening/Baseline MRI showing a mass effect defined as significant compression of the ventricular system and/or a midline shift with associated clinical symptoms deemed inappropriate for the patient to enter a clinical trial. If there is otherwise asymptomatic compression and/or midline shift and the patient fulfills all other criteria, these patients are considered eligible.
• Any condition (medical, social, psychological) that would prevent adequate information and follow-up, including but not limited to clinically relevant psychiatric disorders, legal incapacity, dementia, adults protected by law or altered mental status.
• Presence of poorly controlled seizures, defined as occurring despite SOC or requiring hospitalization.
• Prior anthracycline cumulative dose more than 550 mg/m2.
• Heart disease:
• LVEF <50%
• Unstable angina
• CHF with New York Heart Association (NYHA) classification of 3 or 4
• Patients with baseline QT/QTc interval >480 msec, a history of additional risk factors for torsades de pointes (TdP) (eg, heart failure, hypokalemia, family history of long QT syndrome) and using concomitant medications that significantly prolong the QT/QTc interval
• History of myocardial infarction within 12 months of enrollment
• Severe arrhythmia not controlled by medication
• Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg and/or diastolic BP >100 mmHg) sustained over 2 measurements.
• Known to be positive for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV), human immunodeficiency virus (HIV), COVID-19 (currently positive at time of screening), or any other acute viral, bacterial, or fungal infection (testing not required unless symptomatic or suspected disease).
• Patients with any other uncontrolled intercurrent medical conditions, including but not limited to diabetes mellitus or chronic obstructive pulmonary disease that have not been well controlled by medical management over the prior 3 months are ineligible unless approved by the sponsor.
• Women who are lactating or breastfeeding

Where it is running

• 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
• Piedmont Healthcare — Atlanta, Georgia, United States
• Rush University Cancer Center — Chicago, Illinois, United States
• University of Kentucky — Lexington, Kentucky, United States
• Tulane Cancer Center Clinic — New Orleans, Louisiana, United States
• Tufts Medical Center — Boston, Massachusetts, United States
• UMass (ACC) - Hollings Cancer Center (HCC) — Worcester, Massachusetts, United States
• Mayo Clinic — Rochester, Minnesota, United States
• University of Nebraska Medical Center — Omaha, Nebraska, United States
• Hackensack Meridian Health — Hackensack, New Jersey, United States
• Rutgers University — Piscataway, New Jersey, United States
• Atlantic Healthcare — Summit, New Jersey, United States
• Roswell Park Cancer Center — Buffalo, New York, United States
• Duke University School of Medicine — Durham, North Carolina, United States
• Ohio State University — Columbus, Ohio, United States
• Providence Health — Portland, Oregon, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.