High Grade Gliomas
Conditions
Interventions
Product Name: Berubicin
Product Code: WP 744
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: Berubicin hydrochloride
CAS Number: 293736-67-1
Current Spons
Sponsors
WPD Pharmaceuticals Sp. z o.o.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Written informed consent of the patient’s LAR, and assent when appropriate based on the patient’s age and institutional guidelines, prior to any study-related procedure. 2. Patients must have progressive, refractory, or recurrent HGG (WHO Grade III or IV). 3. Age =2 to 1 related to prior therapies (chemotherapy, radiation therapy, and/or surgery) must be resolved to Grade 1 or baseline level, except for alopecia and sensory neuropathy Grade =2 or other Grade =2 AEs not constituting a safety risk based on the investigator's judgment. 9.For postpubertal patients: Female patients must agree to use highly effective contraception during the period of the study and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use highly effective contraception during the period of the study and for at least 90 days after completion of treatment. Details are provided in the full protocol. 10. Female patients of childbearing potential aged 10 years or older must have a negative serum or urine pregnancy test. 11. MRI of the brain and entire spine (including all sites of disease), within 10 days prior to start of study drug. 12. Corticosteroid dose must be stable or decreasing
Exclusion criteria
Exclusion criteria: 1. Evidence of diffuse leptomeningeal disease or evidence of cerebrospinal fluid (CSF) dissemination. 2. Known additional malignancy that is progressing or has required active treatment within 3 years of start of study drug. 3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Berubicin or its excipients. 4. Patients with any clinically significant, unrelated systemic illness (eg, significant pulmonary, hepatic [including Gilbert’s syndrome], or other organ dysfunction) or psychiatric illness/social situations that would compromise the patient’s ability to tolerate the study drug or study procedures or would likely interfere with the study procedures or results. 5. Any known clinically significant active bacterial, fungal, or viral infection including hepatitis B or hepatitis C, or any underlying disease in the recent past that could compromise enrollment and the safety of the patient. 6. Patient with a history of clinically significant, uncontrolled heart disease and/or repolarization abnormalities as documented by a standard 12-lead electrocardiogram (ECG). 7. Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias, or bradycardia, unless arrhythmia is controlled and after a cardiology consultation has cleared the patient to receive Berubicin. Patients receiving therapeutic agents known to prolong QTinterval will be excluded; however, the use of ondansetron is permitted. Patients with a history of congestive heart failure, myocardial infarction, or stroke in the last 3 months will be excluded. 8. Congenital long QT syndrome or QTc >460 ms. 9. Patients receiving any other anticancer or investigational drug therapy. 10. Prior treatment with bevacizumab. 11. Current or planned participation in a study of another investigational agent or using an investigational device. 12. Requirement for cytochrome P450 3A4 (CYP3A4)-inducing or inhibiting agents, with the exception of corticosteroids. Patients unable to return for follow-up visits or undergo follow-up procedures required to assess toxicity of therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose Escalation Cohorts: To estimate the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of single-agent Berubicin administered after at least 1 prior line of therapy in pediatric patients with progressive, refractory, or recurrent HGG. • Expansion Cohort: To evaluate the safety of Berubicin administered at the MTD or RP2D to pediatric patients with progressive, refractory, or recurrent HGG who have completed at least 1 prior line of therapy.;Secondary Objective: -To define and describe the toxicities associated with single-agent Berubicin administered after at least 1 prior line of therapy to pediatric patients with progressive, refractory, or recurrent HGG. - To characterize the PK of Berubicin and its metabolite, Berubicinol, in a pediatric population. - To estimate the incidence and duration of objective response (as described in Efficacy Outcome Measures) in pediatric patients with progressive, refractory, or recurrent HGG administered Berubicin after at least 1 prior line of therapy. - To estimate the progression-free survival (PFS) and OS in paediatric patients with progressive, refractory, or recurrent HGG administered Berubicin after at least 1 prior line of therapy. -To explore the effects of Berubicin on patient-reported health-related quality of life outcome and neurocognitive functioning using the Paediatric Quality of Life Inventory (PedsQL™) brain tumor module on patients;Primary end point(s): • Dose Escalation Cohorts: MTD and/or RP2D of Berubicin in pediatric patients with progressive, refractory, or recurrent HGG after at least 1 prior line of therapy. • Expansion Cohort: Incidence of AEs at least possibly associated with Berubicin when administered to pediatric patients with progressive, refractory, or recurrent HGG after at least 1 prior line of therapy. ;Timepoint(s) of evaluation of this end point: Primary Endpoint Dose Escalation: MTD/RP2D will be assessed 21 days after last patient in a given cohort rec | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: PK parameters will be evaluated at the same time points as MTD + at the end of the trial. Efficacy parameters (all response parameters) and OS will be evaluated at the End of the trial. ;Secondary end point(s): Secondary Endpoint(s): • Standard PK parameters for Berubicin and its metabolite, Berubicinol, as derived from noncompartmental analysis of plasma drug concentration-time data • Objective response rate (ORR) (CR or PR to Berubicin within 6 months) • Duration of response (DoR) • Proportion of patients achieving CR within 6 months • Proportion of patients achieving PR within 6 months • Best overall response within 6 months • PFS at 6 months • OS at 6 months • OS at end of the study Exploratory Endpoint(s): • PedsQL brain tumor module scores | — |
Countries
Poland
Contacts
Public ContactWPD Pharmaceuticals Sp. z o.o.
WPD Pharmaceuticals Sp. z o.o.
Outcome results
None listed