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Glioblastoma Multiforme, AdultPhase 2NCT04762069

A Study of Berubicin in Adult Subjects With Recurrent Glioblastoma Multiforme

A Phase 2 study testing Berubicin and Lomustine in people with Glioblastoma Multiforme, Adult, run by CNS Pharmaceuticals, Inc. at 48 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma Multiforme, Adult
What is being tested?
Berubicin and Lomustine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
252 participants
Where
48 sitesin 5 countries
Study dates
18 May 2021to 15 Jul 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Renal function: serum creatinine ≤1.5 × ULN or for patients with creatinine levels above the ULN, estimated creatinine clearance of ≥60 mL/min, calculated using the Cockcroft-Gault equation35
  • Activated partial thromboplastin time (aPTT) ≤1.5 × ULN
  • Women of childbearing potential must agree to practice a highly effective method of contraception beginning at least 28 days before the start of treatment until at least 6.25 months after the last dose of study drug. Male study patients and their female sexual partners of childbearing potential must agree to practice a highly effective method of contraception starting from the time of informed consent until at least 3.5 months (no less than 104 days) after the last dose of study drug.
  • A woman of childbearing potential is defined as a woman who is not permanently sterilized or postmenopausal. Postmenopausal is defined as 12 months with no menses without an alternative medical cause.
  • Women of childbearing potential must have a negative serum or urine pregnancy test at Screening.
  • A highly effective method of birth control is defined as one which results in a low failure rate (ie, less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence, or vasectomized partner. For patients using a hormonal contraceptive method, information regarding all medications being administered to the patient and their potential effects on the contraceptive should be addressed.
  • Patients with prior malignancies must be disease-free for ≥5 years. Curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; or prostate cancer as well as benign tumors that will not interfere with the treatment plan at the time of screening are allowed.

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

48 sites in 5 countries.

48 sites in 5 countries

United States32 sites

  • Piedmont Healthcare

    Atlanta, Georgia, 30309

  • Texas Oncology PA

    Austin, Texas, 78758

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Roswell Park Cancer Center

    Buffalo, New York, 14263

  • Rush University Cancer Center

    Chicago, Illinois, 60612

  • Ohio State University

    Columbus, Ohio, 43210

  • Baylor Research Institute

    Dallas, Texas, 75246

  • Duke University School of Medicine

    Durham, North Carolina, 27710

  • HCA Healthcare Research Institute

    Englewood, Colorado, 80113

  • Hackensack Meridian Health

    Hackensack, New Jersey, 07601

  • Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • University of Texas Health Science Center at Houston

    Houston, Texas, 77027

  • Baptist MD Anderson Cancer Center

    Jacksonville, Florida, 32207

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • University of Kentucky

    Lexington, Kentucky, 40536

  • University of Arkansas

    Little Rock, Arkansas, 72205

  • Southern California Permanente Medical Group

    Los Angeles, California, 90027

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53705

  • Baptist Miami

    Miami, Florida, 33176

  • Tulane Cancer Center Clinic

    New Orleans, Louisiana, 70112

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • University of California Irvine

    Orange, California, 92868

  • Rutgers University

    Piscataway, New Jersey, 08854

  • Providence Health

    Portland, Oregon, 97225

  • Mayo Clinic

    Rochester, Minnesota, 550905

  • Huntsman Cancer Center

    Salt Lake City, Utah, 84112

  • University of Califonia San Diego Moores Cancer Center

    San Diego, California, 92093

  • University of California San Francisco

    San Francisco, California, 94143

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

    Santa Monica, California, 90404

  • Swedish Medical Center

    Seattle, Washington, 98122

  • Atlantic Healthcare

    Summit, New Jersey, 07901

  • UMass (ACC) - Hollings Cancer Center (HCC)

    Worcester, Massachusetts, 01655

Other trials in United States

France7 sites

  • Hopital Pierre Wertheimer

    Lyon

  • Hopital de La Timone

    Marseille

  • Institut de Recherche en Cancerologie de Montpellier

    Montpellier

  • Hopital Pitie-Salpetriere

    Paris

  • Institut de Cancerologie de l'Ouest

    Saint-Herblain

  • nstitut Universitaire du Cancer de Toulouse-

    Toulouse

  • Institut de Cancerologie Gustave-Roussy

    Villejuif

Other trials in France

Spain6 sites

  • Hospital Universitari Germans Trias i Pujol

    Badalona

  • Hospital Duran i Reynals

    L'Hospitalet de Llobregat

  • Hospital Ramón y Cajal

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Regional Universitario de Malaga Carlos Haya

    Málaga

  • Hospital Universitario Virgen Macarena

    Seville

Other trials in Spain

Italy2 sites

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

    Bologna

  • Istituto Clinico Humanitas

    Milan

Other trials in Italy

Switzerland1 site

  • University Hospital Zurich

    Zurich, 8091

Other trials in Switzerland

About this study

Official title: A Multicenter, Open-Label Study With a Randomized Control Arm of the Efficacy, Safety, and Pharmacokinetics of Intravenously Infused Berubicin in Adult Patients With Recurrent Glioblastoma Multiforme After Failure of Standard First Line Therapy

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.

Read the 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.

Being tested
Berubicin, Lomustine
Keywords
Glioblastoma Multiforme, Glioblastoma, Brain Cancer, Brain Tumor
Medical subject headings
Glioblastoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BerubicinDrug

    Also called Berubicin Hydrochloride

    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.

  • LomustineDrug

    Also called Lomustine Capsules, CCNU, CeeNU, Gleostine

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

Study groups in NCT04762069
Study groupRoleWhat they receive
BerubicinExperimentalBerubicin 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.
Receives: Drug: Berubicin
Lomustine (CCNU, CeeNU®, or Gleostine®) capsulesActive comparatorLomustine (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.
Receives: Drug: Lomustine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Through study completion an average of 4 years.

Secondary outcomes (14)

  1. Progression Free Survival

    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

    Measured: Through study completion an average of 4 years.

  2. Event Free Survival

    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)

    Measured: Through study completion an average of 4 years.

  3. Overall Response Rate

    To assess the effect of berubicin on overall response rates (ORR) in adult patients with GBM after failure of standard first line therapy

    Measured: Through study completion an average of 4 years.

  4. Safety of the Recommended Phase 2 Dose of Berubicin

    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.

    Measured: 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).

  5. Plasma Pharmacokinetics Cmax

    Maximum plasma concentration of Berubicin

    Measured: Through study completion an average of 4 years.

  6. Plasma Pharmacokinetics tmax

    Time from each dose to reach the maximum plasma concentration

    Measured: Through study completion an average of 4 years.

  7. Plasma Pharmacokinetics AUC0-tau

    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

    Measured: Through study completion an average of 4 years.

  8. Plasma Pharmacokinetics AUC0-last

    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

    Measured: Through study completion an average of 4 years.

  9. Plasma Pharmacokinetics AUC0-∞

    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

    Measured: Through study completion an average of 4 years.

  10. Plasma Pharmacokinetics t1/2

    elimination half-life associated with the terminal slope (λz) of the log-linear drug concentration-time curve, calculated as ln(2)/λz

    Measured: Through study completion an average of 4 years.

  11. Plasma Pharmacokinetics CL

    apparent total body clearance

    Measured: Through study completion an average of 4 years.

  12. Plasma Pharmacokinetics Vz

    apparent volume of distribution

    Measured: Through study completion an average of 4 years.

  13. Plasma Pharmacokinetics Css

    Average concentration, calculated as the geometric mean of concentrations over the 72-hour dosing interval

    Measured: Through study completion an average of 4 years.

  14. Plasma Pharmacokinetics Rac

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

    Measured: Through study completion an average of 4 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2021
  2. Study start18 May 2021
  3. Primary completion27 Apr 2026 (estimated)
  4. Study completion15 Jul 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Open-Label Study with a Randomized Control Arm
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
252 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04762069
Sponsor's protocol ID
CNS-201
Status last verified
Apr 2026
First submitted
11 Nov 2020
Last updated
15 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Study data will be shared with WPD Pharmaceuticals, Inc., sub-licensee of Berubicin.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Berubicin and Lomustine in people with Glioblastoma Multiforme, Adult, run by CNS Pharmaceuticals, Inc. at 48 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States, France, Spain, Italy, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: Through study completion an average of 4 years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04762069.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2026.

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