Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Disease Attributes

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

The first 18 patients will undergo a pK assessment of Berubicin and it's active metabolite Berubicinol during the dosing days of the first two cycles. After 18 patients are done n intern analysis will new performed.

Berubicin intravenously infused will be administered at a dose of 7.1 mg/m2 as free base (equivalent to 7.5 mg/m2 Berubicin HCl) as a 2-hour intravenous (IV) infusion once daily for 3 consecutive days followed by 18 days off study drug (each cycle = 21 days).

Berubicin Hydrochloride

Koordynator Badania

Ewa Szutowicz, MD

Damian Kucharczyk

Bartosz Spławski, MD

Andrzej Kawecki, Prof.

This is a multicenter, open-label, Phase 1b/2 efficacy and safety study of Berubicin utilizing a Simon's 2-stage design to confirm the efficacy (or futility) of a single arm of Berubicin treatment, administered at the recommended Phase 2 dose (RP2D) identified in Phase 1 studies (7.5 mg/m2 Berubicin HCl), on the endpoint of ORR in up to approximately 61 patients. A central reader will determine the radiologic responses for each patient according to m RANO criteria. The responder criteria for this Simon's design will be based on objective response criteria defined as individual patients achieving CR or PR per m-RANO criteria within 6 months from baseline.

The planned minimum duration of the study for an individual patient is approximately 11 weeks as follows:

* A 4-week Screening Period
* A 3-week Treatment Period (ie, one 3 week treatment cycle)
* A 4-week End-of-Treatment follow-up Period after the last dose The 3-week treatment cycles may be repeated in the absence of clinical and/or neurological deterioration, or unacceptable toxicity, and as long as both the patient and investigator agree that further therapy is in the patient's best interest.

After the End-of-Treatment follow-up visit, patients will enter a Post-Study follow-Up Period of up to approximately 2 years.

Berubicin in Adult Patients With Recurrent Glioblastoma Multiforme (WHO Grade IV)

A Multicenter, Open-Label Study of the Efficacy, Safety, and Pharmacokinetics of Intravenously Infused Berubicin in Adult Patients With Recurrent Glioblastoma Multiforme (WHO Grade IV) After Failure of Standard First Line Therapy

To confirm the efficacy (or futility) of Berubicin treatment on objective response rate (ORR) defined as CR or PR per modified Response Assessment in Neuro-Oncology (m RANO) criteria in patients with GBM (World Health Organization \[WHO\] Grade IV) that has recurred after standard initial therapy, based on Simon's 2-stage design

• 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 stable disease , disease progression, death, or discontinuation of treatment for any reason (eg, toxicity, intolerance, disease-related conditions, or failure to respond). Safety will be monitored by a safety review committee (SRC). The SRC will review PK and safety data from the first 2 cycles of treatment for the first approximately 18 patients (i.e., Stage 1) of this study

intensive pK assessment of Berubicin and it's active metabolite will be performed during the dosing days of the first two cycles , this will be folowed by an interim analysis at 18 patients time point.Plasma samples will be collected from the first approximately 18 patients enrolled, and concentrations of Berubicin and its metabolite, berubicinol, will be measured

Screening/baseline MRI scans will be evaluated by a central reader for validation of eligibility and documentation of initial measurements. During the Treatment Period, the baseline scan will be compared with scans at 6-week (2-cycle) intervals for evaluation of disease by the investigator as well as the central reader according to m-RANO criteria.

Worldwide Clinical Trials

National Center for Research and Development, Poland

WPD Pharmaceuticals Sp. z o.o.

Berubicin will be administered as 1-hour infusions each day for 3 consecutive days followed by 18 days off drug (ie, 21-day cycles). The starting dose is based on population PK modeling of data from adult studies and will be 1.20 mg/m2 (Dose Level 1). During the study, PK data will be incorporated into a PK model on an ongoing basis and may be used to inform dose escalation decisions

This is a Phase 1, multicenter, open-label, dose escalation study of intravenous Berubicin in pediatric patients. The purpose of this first-in-pediatrics study is to examine the safety, tolerability, and PK of Berubicin and to estimate its MTD and/or RP2D when administered to pediatric patients with progressive, refractory, or recurrent HGG who have completed at least 1 standard line of therapy. This study will also make a preliminary assessment of the antitumor activity of Berubicin in this patient population. An exploratory evaluation of quality of life will also be performed

This is a Phase 1, multicenter, open-label, dose escalation study of intravenous Berubicin in pediatric patients. The purpose of this first-in-pediatrics study is to examine the safety, tolerability, and PK of Berubicin and to estimate its MTD and/or RP2D when administered to pediatric patients with progressive, refractory, or recurrent HGG who have completed at least 1 standard line of therapy. This study will also make a preliminary assessment of the antitumor activity of Berubicin in this patient population. An exploratory evaluation of quality of life will also be performed.

This open-label, nonrandomized study is composed of a series of Dose Escalation Cohorts followed by an Expansion Cohort. The Dose Escalation Cohorts will utilize a standard "rules based" 3+3 design. A safety review committee (SRC) composed of, at a minimum, the principal investigators, the medical monitor(s), the sponsor's responsible medical officer (s), and an external expert in pediatric oncology will review all available study data at regular intervals and will make recommendations to the sponsor regarding dose escalations. Patients enrolled in the Expansion Cohort will be administered the MTD or RP2D identified during dose escalation. Safety, PK, efficacy, and quality of life evaluations will be performed for all patients throughout the study.

Berubicin will be administered as 1-hour infusions each day for 3 consecutive days followed by 18 days off drug (ie, 21-day cycles). The starting dose is based on population PK modeling of data from adult studies and will be 1.20 mg/m2 (Dose Level 1). During the study, PK data will be incorporated into a PK model on an ongoing basis and may be used to inform dose escalation decisions.

Dose Escalation and Stopping Rules: The Dose Escalation Cohorts will utilize a standard 3+3 design to determine an MTD and/or RP2D. All available information, including safety, PK, and efficacy, will be taken into account when making decisions regarding dose escalation. The 3 + 3 dose escalation procedures will be based on the following:

Enroll 3 patients initially. If no dose-limiting toxicities (DLTs; as defined in Safety Outcome Measures) occur, escalate dose to next dose level cohort.

If 1 patient out of 3 experiences a DLT, expand cohort up to 6 patients. If 1 patient out of 6 experiences a DLT, escalate to next dose level cohort. If ≥2 patients out of 6 experience a DLT, the MTD will have been exceeded; stop dose escalation, and review the next lower dose cohort. This may require enrollment of a further 3 patients if only 3 were dosed at a previous dose level.

Note that patients who experience a DLT may not necessarily be required to discontinue from the study, based on the judgement of the investigator. Patients who discontinue from a Dose Escalation Cohort before the end of the DLT evaluation period for reasons other than a DLT will be replaced.

Once the MTD or RP2D has been established, an Expansion Cohort will be initiated. Patients enrolled in the Expansion Cohort will receive the MTD or RP2D identified during Dose Escalation.

Patients may continue to receive additional cycles of Berubicin in the absence of clinical and/or neurologic deterioration or unacceptable toxicity as long as both the patient's legally authorized representative (LAR) and investigator agree that further therapy is in the patient's best interest. Patients with radiographic evidence of progression but who are clinically stable and are not experiencing significant neurologic decline (based on investigator assessments and Neurological Assessment in Neuro-Oncology \[NANO\] criteria) may remain on the study at the discretion of the investigator.

Patients will return for a follow-up assessment on Day 28, approximately 25 days after the last dose of Berubicin.

All patients, including those who discontinue study treatment for any reason, will continue to be followed (Post-Study Follow up) for further anti-tumor treatment and survival every 3 months until death, loss to follow-up, withdrawal of consent, or end of the study.

A Multicenter, Study of the Safety and Pharmacokinetics of Intravenously Infused Berubicin in Pediatric Patients With Progressive, Refractory, or Recurrent High Grade Gliomas

A Phase 1, Multicenter, Open-label, Dose Escalation Study of the Safety and Pharmacokinetics of Intravenously Infused Berubicin in Pediatric Patients With Progressive, Refractory, or Recurrent High Grade Gliomas

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.

To completely document the assessment of response, the measurements of the longest tumor dimension, and its perpendicular, of all target lesions should be recorded for the baseline and all subsequent follow-up exams. Changes in nontarget lesions and newly occurring lesions should also be described. The same method of assessment and the same technique should be used at baseline and during follow-up.

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.

Tumor response criteria are determined by changes in size using the longest tumor dimension and its perpendicular. If multiple measurable lesions are present, a minimum of the 2 largest lesions should be measured; a maximum of 5 should be selected as target lesions. Target lesions should be selected on the basis of size and suitability for accurate repeated measurements. All other lesions will be followed as nontarget lesions. Only solid components of cystic/necrotic tumors should be measured.

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 The MTD is empirically defined as the highest dose level at which 6 patients have been treated with at most 1 patient experiencing a DLT and the next higher dose level has been determined to be not tolerated (≥2 out of 6 patients experience a DLT). The MTD estimation will be limited to evaluable patients and toxicity assessments from the first cycle of Berubicin treatment (21 days).

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 The RP2D is a multifactorial endpoint that considers toxicity as well as additional determinants (eg, efficacy, pharmacodynamics) to define the optimal Phase 2 dose on the basis of available clinical safety and efficacy data. It is usually a dose in which there is ≤20% dose-limiting toxicity; however, it can be further defined by exploration of doses that maximize efficacy in the presence of minimal safety concerns.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Berubicin in Adult Patients With Recurrent Glioblastoma Multiforme (WHO Grade IV)	NCT04915404	Recurrent Gliob...	Berubicin Hydro...	18 Years -	WPD Pharmaceuticals Sp. z o.o.
Berubicin in Adult Patients With Recurrent Glioblastoma Multiforme (WHO Grade IV)	NCT04915404	Recurrent Gliob...	Berubicin Hydro...	18 Years -	WPD Pharmaceuticals Sp. z o.o.
Berubicin in Adult Patients With Recurrent Glioblastoma Multiforme (WHO Grade IV)	NCT04915404	Recurrent Gliob...	Berubicin Hydro...	18 Years -	WPD Pharmaceuticals Sp. z o.o.
A Multicenter, Study of the Safety and Pharmacokinetics of Intravenously Infused Berubicin in Pediatric Patients With Progressive, Refractory, or Recurrent High Grade Gliomas	NCT05082493	High Grade Glio...	Berubicin Hydro...	2 Years - 18 Years	WPD Pharmaceuticals Sp. z o.o.

Spots Global Cancer Trial Database for berubicin hydrochloride