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

NCT04915404 | Terminated Phase 1 DMC

• 1 other identifier: WPD-201
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Recurrent Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

• objective response rate (ORR)

  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

  6 months

Secondary Outcomes (3)

• • To confirm the safety profile of Berubicin that was characterized during Phase 1 studies and assess the effect of Berubicin on event-free survival (EFS)

  6 months

• • To confirm the pharmacokinetic (PK) profile of Berubicin and its metabolite, berubicinol, that was characterized during Phase 1 studies

  6 months

• • To assess the effect of Berubicin on disease control rate (DCR) defined as CR or PR or stable disease [SD] per m-RANO criteria in patients with GBM after failure of standard first line therapy

  12 months

Study Arms (1)

pK Assessment of Berubicin and its active metabolite

EXPERIMENTAL

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.

Drug: Berubicin Hydrochloride

Interventions

Berubicin Hydrochloride DRUG

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).

pK Assessment of Berubicin and its active metabolite

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Written informed consent 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.
• A diagnosis of GBM (WHO Grade IV) confirmed by:
• Archived paraffin-embedded tissue (approximately 10 unstained slides or a tumor block) from initial resection for local review of tumor diagnosis OR
• A tumor tissue form indicating diagnosis from initial resection of glioblastoma completed and signed by a pathologist and/OR
• Tumor tissue from re-resection, managed as above (a OR b)
• Measurable disease is required with documented unequivocal evidence of tumor recurrence or progression following prior therapy, confirmed by the following:
• Recurrent GBM as documented by the principal investigator (PI). In case of recent interim debulking surgery, the histopathological verification of the resected tissue as recurrent tumor automatically qualifies the patient as eligible for the trial.
• KPS reduction of 10 units while on stable or increasing doses of corticosteroids as documented by the PI
• Subject MRI meets at least two of the following three criteria as determined by central review:
• Presence of measurable disease: the lesion is ≥10 mm in both maximum perpendicular diameters
• Evidence of unequivocal tumor recurrence or progression following prior therapy as determined by a 10% increase in the sum of the products of perpendicular diameters of the contrast-enhancing lesions
• Substantial increase in the perilesional oedema as shown in T2/FLAIR images.
• All contrast enhancing disease is located supratentorially
• O\[6\] methylguanine-DNA methyltransferase (MGMT) methylation status must be available, or able to be determined from existing tumor tissue; results of routinely used methods for MGMT methylation testing (e.g., methylation-specific polymerase chain reaction \[MSPCR\] or quantitative polymerase chain reaction \[PCR\]) are acceptable.

Sponsors & Collaborators

• WPD Pharmaceuticals Sp. z o.o.: lead
• Worldwide Clinical Trials: collaborator
• National Center for Research and Development, Poland: collaborator

Study Sites (2)

Uniwersyteckie Centrum Kliniczne Klinika Onkoligii i Radioterapii

Gdansk, 80-214, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie,Państwowy Instytut Badawczy w Warszawie,Klinika Nowotworów Głowy i Szyi

Warsaw, 02-781, Poland

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2021
• First Posted: June 7, 2021
• Study Start: December 7, 2022
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: June 6, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

PL (2)