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Recurrent Glioblastoma MultiformePhase 1/2NCT04915404

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

A Phase 1/2 study testing Berubicin Hydrochloride in people with Recurrent Glioblastoma Multiforme, run by WPD Pharmaceuticals Sp. z o.o. at 2 sites in Poland.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Glioblastoma Multiforme
What is being tested?
Berubicin Hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
2 sitesPoland
Study dates
7 Dec 2022to 30 Dec 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 1 country.

Poland2 sites

  • Uniwersyteckie Centrum Kliniczne Klinika Onkoligii i Radioterapii

    Gdansk, 80-214

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

    Warsaw, 02-781

Other trials in Poland

About this study

Official title: 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

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.

Read the 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.

Being tested
Berubicin Hydrochloride
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Berubicin HydrochlorideDrug

    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).

Study groups in NCT04915404
Study groupRoleWhat they receive
pK Assessment of Berubicin and its active metaboliteExperimentalThe 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.
Receives: Drug: Berubicin Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6 months

Secondary outcomes (3)

  1. • 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)

    • 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

    Measured: 6 months

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

    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

    Measured: 6 months

  3. • 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

    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.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2021
  2. Study start7 Dec 2022
  3. Primary completion30 Dec 2023
  4. Study completion30 Dec 2023

Why it stopped: Business decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04915404
Sponsor's protocol ID
WPD-201
Status last verified
Jun 2024
First submitted
23 Feb 2021
Last updated
6 Jun 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Berubicin Hydrochloride in people with Recurrent Glioblastoma Multiforme, run by WPD Pharmaceuticals Sp. z o.o. at 2 sites in Poland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Business decision). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

objective response rate (ORR) (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04915404.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2024.

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