- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04915404
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Gdańsk, Poland, 80-214
- Recruiting
- Uniwersyteckie Centrum Kliniczne Klinika Onkoligii i Radioterapii
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Contact:
- Koordynator Badania
- Phone Number: +48 58 584 44 09
- Email: clinicaltrials@wpdpharmaceuticals.com
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Principal Investigator:
- Ewa Szutowicz, MD
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Warszawa, Poland, 02-781
- Recruiting
- Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie,Państwowy Instytut Badawczy w Warszawie,Klinika Nowotworów Głowy i Szyi
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Contact:
- Damian Kucharczyk
- Phone Number: +48 22 546 23 76
- Email: clinicaltrials@wpdpharmaceuticals.com
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Contact:
- Bartosz Spławski, MD
- Phone Number: +48 22 546 29 97
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Principal Investigator:
- Andrzej Kawecki, Prof.
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Patients will be eligible for the study if they meet all of the following inclusion criteria and none of the exclusion criteria.
Inclusion criteria
- 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.
- No more than 1 prior line of treatment (e.g., 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.
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 chemotherapy or 6 weeks after the end of treatment with nitrosoureas
- 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
- 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 as confirmed by the PI.
- Immunosuppressive therapies allowed include the use of topical, inhalational, ophthalmic, or intra-articular glucocorticoids, or the use of physiologic replacement doses of glucocorticoids.
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 ≥3000/mm³, absolute neutrophil count (ANC) ≥1500/mm³, platelet count ≥75,000/mm³, 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, or estimated creatinine clearance of ≥60 mL/min/1.73 m2, calculated using the Cockcroft Gault formula
- 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 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.
- A highly effective method of birth control is defined as one which results in a low failure rate (i.e., 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 effect on the contraceptive should be addressed.
- Patients with prior malignancies must be disease-free for ≥5 years. However, curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; or prostate cancer curatively treated at the time of screening is allowed.
Exclusion Criteria
- Unable or not willing to comply with the protocol regulations.
- Any additional concurrent radiation therapy or chemotherapy (including but not limited to temozolomide [TMZ]) for recurrent or progressive GBM after a first line treatment.
- Prior treatment with bevacizumab.
- The presence of IDH mutation prior to enrollment
- Screening MRI showing a mass effect defined as significant compression of the ventricular system and/or a midline shift (≥10 mm) as determined by central MRI review.
- 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.
- Presence of poorly controlled seizures, defined as occurring despite standard of care (SOC) or requiring hospitalization.
- Widespread or focal leptomeningeal disease measuring ≥10mm by ≥10mm.
- Prior anthracycline cumulative dose more than 550 mg/m2.
Heart disease:
- LVEF <50%
- Unstable angina
- Congestive heart failure 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) (e.g., 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.
- Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg and/or diastolic BP >100 mmHg).
- Known to be positive for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV), human immunodeficiency virus (HIV), coronavirus disease-2019 (COVID-19) or any other acute viral, bacterial, or fungal infection (testing not required unless symptomatic or suspected disease).
- 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.
WPD reserves the right to deny any patient enrollment based upon any potential safety concern(s) or factors that could confound the study results.
Note: Investigator (PI or designee) review of all screening assessment results is required to determine eligibility prior to Berubicin administration.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: pK Assessment of Berubicin and its active metabolite
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.
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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).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
objective response rate (ORR)
Time Frame: 6 months
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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
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6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
• 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)
Time Frame: 6 months
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• 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
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6 months
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• To confirm the pharmacokinetic (PK) profile of Berubicin and its metabolite, berubicinol, that was characterized during Phase 1 studies
Time Frame: 6 months
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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
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6 months
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• 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
Time Frame: 12 months
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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.
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12 months
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- WPD-201
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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