Glioblastoma Multiforme (WHO Grade IV) MedDRA version: 20.0 Level: PT Classification code 10018337 Term: Glioblastoma multiforme System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Berubicin
Product Code: WP 744
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: Berubicin
CAS Number: 293736-67-1
Current Sponsor code: WP 744
Concentrati
Sponsors
CNS Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent [...] 2. At least 18 years of age. 3. 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. 4. Recurrent GBM as evaluated by RANO criteria, confirmed by central review, as follows: Measurable disease is required with documented unequivocal evidence of tumor recurrence or progression following prior therapy (ie, 25% increase in the sum of the products of perpendicular diameters of the contrast-enhancing lesions while on stable or increasing doses of corticosteroids; however, these changes should not be due to changes in the dose of corticosteroids) as documented by the investigator. 5. The tumor is localized supratentorially. 6. The lesion (or sum of lesions) does not exceed 50 cm3 in volume. 7. 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. 8. 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). A second debulking surgery during the first line treatment is acceptable. In addition, treatment with tumor treating fields (TTFields; Optune?) is acceptable if provided as first line therapy. 9. 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: a. 12 weeks from the completion of radiation (to reduce risk of pseudoprogression), unless progression is confirmed by biopsy b. 4 weeks from the end of any previous of chemotherapy or 6 weeks after the end of treatment with nitrosoureas c. 4 weeks from the end of any TTFields treatment d. 4 weeks from any major surgery (maximal debulking surgery, either gross total resection or partial resection) or significant traumatic injury, and any surgery incisions or wounds must be completely healed 10. 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. 11. Immunosuppressive therapies allowed include the use of topical, inhalational, ophthalmic or intra-articular glucocorticoids, or the use of physiologic replacement doses of glucocorticoids. 12. 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: a. Hematopoietic function: total white blood cell (WBC) count =3000/mm³, absolute neutrophil count (ANC) =1500/mm³, platelet count =75,000/mm³, hemoglobin =10 g/dL b. 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 c. 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-
Exclusion criteria
Exclusion criteria: 1. Unable or not willing to comply with the protocol regulations. 2. Any additional concurrent radiation therapy or chemotherapy (including but not limited to TMZ) for recurrent or progressive GBM after a first line treatment. 3. Prior treatment with bevacizumab. 4. Prior treatment with lomustine. 5. Screening MRI showing a mass effect defined as significant compression of the ventricular system and/or a midline shift (=10 mm)34 confirmed by central MRI review. 6. 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 or altered mental status. 7. Presence of poorly controlled seizures, defined as occurring despite SOC or requiring hospitalization. 8. Prior anthracycline cumulative dose more than 550 mg/m2. 9. Heart disease: a. LVEF 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 e. History of myocardial infarction within 12 months of enrollment 10. Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg and/or diastolic BP >100 mmHg). 11. 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). 12. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of berubicin compared with lomustine on OS in adult patients with GBM (WHO Grade IV) that has recurred after standard initial therapy.;Secondary Objective: To assess the effect of berubicin on PFS per RANO criteria in patients with GBM after failure of standard first line therapy, defined as the length of time from the initiation of study drug administration to disease progression based on MRI scan./To assess the effect of berubicin on 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./To assess the effect of berubicin on ORR and individual components (ie, CR alone, PR alone) as well as DCR defined as CR or PR or SD per RANO criteria in adult patients with GBM after failure of standard first line therapy./To assess the safety of the RP2D of berubicin given as a 2-hour IV infusion once daily for 3 consecutive days followed by 18 days off study drug (each cycle = 21 days) by the incidence and severity of AEs according to NCI-CTCAE, Version 5.0./To confirm the pharmacokinetics (PK) of berubicin and its metabolite, berubicinol.;Primary end point(s): The primary endpoint of this study is OS.;Timepoint(s) of evaluation of this end point: through study completion, an average of 4 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •PFS, defined as the length of time from the initiation of study drug administration to disease progression based on MRI scan • 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) • ORR, defined as CR or PR per RANO criteria • DCR, defined as CR or PR or SD per RANO criteria; SD is defined as lack of progression of disease based on MRI scan obtained at least 6 weeks after initiation of therapy The PK endpoint of this study is: • Standard PK parameters for berubicin and its metabolite, berubicinol, as derived from noncompartmental analysis of plasma drug concentration-time data.;Timepoint(s) of evaluation of this end point: through study completion, an average of 4 years | — |
Countries
France, Italy, Spain, Switzerland, United States
Contacts
Public ContactZena Muzyczenko
CNS Pharmaceuticals, Inc.
Outcome results
None listed