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Recurrent High-grade GliomaPhase 1NCT06463184

Study to Assess Xevinapant in Preoperative Subjects With Recurrent High-Grade Glioma (rHGG)

A Phase 1 study testing Xevinapant in people with Recurrent High-grade Glioma, run by H. Lee Moffitt Cancer Center and Research Institute.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Researchers will investigate the ability of Xevinapant to cross the blood-brain barrier and exert anti-tumor effects on rHGG through activation of apoptosis. Researchers hypothesize that oral administration of Xevinapant has acceptable safety and tolerability in patients with recurrent HGG and demonstrate… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent High-grade Glioma
What is being tested?
Xevinapant
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
22 Jul 2024to Jun 2027
Phase
Phase 1
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

  • Male or female ≥ 18 years of age (or based on the country legal age limit for adults) on day of signing the Informed Consent Form (ICF).
  • Patient must have histologically confirmed diagnosis of: WHO grade III or IV glioma or glioblastoma or gliosarcoma. This definition also includes anaplastic astrocytoma, anaplastic oligodendroglioma, and anaplastic mixed glioma.
  • Radiographic evidence of tumor recurrence.
  • Contrast enhancing tumor that is amenable to surgical resection
  • Patient must be able to understand and willing to sign an informed consent.
  • Patient must have Karnofsky performance status (KPS) of ≥70 or Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
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  • Able to swallow liquids or has an adequately functioning feeding tube, gastrostomy or jejunostomy placed.
  • Adequate hematologic, renal, and hepatic function as indicated by the protocol.
  • Women of childbearing potential (according to recommendations of the Clinical Trial Facilitation Group) must have a negative serum pregnancy test at screening and must not be breastfeeding. Women of childbearing potential must agree to use highly effective contraceptive method(s) from ICF signature to 6 months after the last administration of chemotherapy or 3 months after last dose of xevinapant. Non-sterilized males who are sexually active with a female partner of childbearing potential must agree to use condom and spermicide from ICF signature to 6 months after the last administration of chemotherapy or 3 months after the last dose of xevinapant. Because male condom and spermicide is not a highly effective contraception method, it is required that female partners of a male study subject use highly effective contraceptive method(s) throughout this period. Male subjects must refrain from donating sperm during the clinical study and for 6 months after the last administration of chemotherapy or 3 months after the last dose of xevinapant. If not done previously, cryopreservation of sperm prior to receiving chemotherapy or xevinapant is advised to male patients with a desire to have children.
  • Subject may or may not have archived primary tumor biopsies or surgical specimens, or biopsies of recurrence tumor for exploratory translational studies. We will enroll at least 4-6 subjects with archival tissue for biomarker/PD studies. For those with archival tissue, at least 10 unstained FFPE tissue slides or a tissue block should be available for enrollment. If less material is available, subject could still be eligible after discussion with the Principal Investigator who will assess and confirm that there is sufficient material for key evaluations.

Who cannot join

  • Use within 14 days prior to randomization or requirement for ongoing treatment with any drug(s) on the prohibited medication list (see "prohibited concomitant drugs" in section 6.5).
  • Known history of infection with HIV. If unknown history of HIV, an HIV screening test is to be performed and subjects with positive serology for HIV-1/2 must be excluded.
  • Known chronically active HBV or HCV infection. If unknown status, the following tests are to be performed and subjects with positive serology must be excluded: A) HBV screening tests: both HBV sAg and Anti-HepB core IgG. B) HCV screening tests: both HCV-antibody and positive viral load HCV-RNA by PCR.
  • Other infections (viral and/or bacterial and/or mycotic) requiring systemic treatment.
  • Live-attenuated vaccinations within 30 days prior to first investigational treatment administration.
  • Ongoing uncontrolled infection requiring intravenous antibiotic therapy within 1 week prior to randomization.
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  • Documented weight loss of >10% during the last 4 weeks prior to randomization (unless adequate measures are undertaken for nutritional support), OR plasmatic albumin < 3.0 g/dL. No albumin transfusions are allowed within 2 weeks before randomization.
  • Active uncontrolled inflammatory disease (including rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, severe extensive psoriasis, and other autoimmune diseases) requiring ongoing treatment with anti-TNF medication.
  • Any concomitant medication known to prolong the QT interval that cannot be discontinued or replaced by safe alternative medication within 7 days prior to start of treatment.
  • Known allergy to Xevinapant or any excipient known to be present in active formulation.
  • Non-compensated or symptomatic liver cirrhosis (Child-Pugh score: B or C).
  • Treatment with an investigational agent or use of an investigational device within 4 weeks of the first dose of study treatment.
  • Known gastrointestinal disorder with clinically established malabsorption syndrome and major gastrointestinal surgery that may limit oral absorption.
  • Active gastrointestinal bleeding, or any other uncontrolled bleeding requiring more than 2 red blood cell transfusions or 4 units of packed red blood cells within 4 weeks prior to randomization.
  • Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: A) Ongoing or history of uncontrolled or symptomatic ischemic myocardiopathy within 6 months prior to randomization. B) Known left ventricular ejection fraction <50%, left ventricular hypertrophy, ventricular arrhythmias, bradycardia (heart rate < 50 bpm). C) History of myocardial infarction, or severe/unstable angina, within 6 months prior to randomization. D) New York Heart Association grade ≥ 3 congestive heart failure. E) Congenital long QT syndrome. F) Family history of long QT syndrome. G) Symptomatic pulmonary embolism within 6 months prior to randomization. H) Ongoing or known history of transient ischemic attacks or stroke within 6 months prior to randomization. I) QTc using Fridericia's formula (QTcF) interval > 470 ms.
  • Symptomatic pulmonary disease requiring continuous or intermittent oxygen supply.
  • History of another malignancy within the last 3 years prior to randomization, with the exception of completely resected non-melanoma cell skin cancer outside the head and neck area or completely resected stage I breast cancer, or completely resected in-situ non-muscular invasive bladder, cervix and/or uterine carcinomas.
  • Any ongoing condition or disorder, before randomization, including drug(s) or alcohol abuse, which in the judgment of the Investigator would make the patient inappropriate for entry into the study or precluding his/her ability to comply with study procedures.

About this study

Official title: A Phase 1, Open-Label Window-of-Opportunity Study to Assess the Pharmacokinetics, Pharmacodynamics and Central Nervous System (CNS) Penetration of Xevinapant in Preoperative Subjects With Recurrent High-Grade Glioma (rHGG)

Researchers will investigate the ability of Xevinapant to cross the blood-brain barrier and exert anti-tumor effects on rHGG through activation of apoptosis. Researchers hypothesize that oral administration of Xevinapant has acceptable safety and tolerability in patients with recurrent HGG and demonstrate pharmacokinetic and pharmacodynamic effects in HGG tumors. To that end, Researchers will engage in a phase I "window of opportunity" translational clinical trial in patients undergoing a clinically-indicated craniotomy for resection of recurrent tumors to evaluate the impact of treatment on rHGG.

Being tested
Xevinapant
Medical subject headings
Glioma

What participants receive

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

  • XevinapantDrug

    Also called Debio 1143

    Xevinapant is an investigational medication, taken orally, that promotes cancer cell death via apoptosis.

Study groups in NCT06463184
Study groupRoleWhat they receive
Xevinapant TreatmentExperimentalParticipants will be given a course of orally administered Xevinapant at 400 mg once daily for 4 consecutive days, prior to undergoing clinically indicated tumor resection.
Receives: Drug: Xevinapant

What is being measured

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

  1. Concentration of Xevinapant

    Concentration of unbound Xevinapant in brain tumor tissue in an exploratory manner (within contrast enhancing tumor as well as non-enhancing tumor, wherever possible) at the time of planned salvage resection.

    Measured: Within 48 hours of last dose of Xevinapant.

  2. Concentration max (Cmax)

    Maximum observed plasma concentration of Xevinapant.

    Measured: Within 48 hours of last dose of Xevinapant.

Secondary outcomes (1)

  1. Occurrence of AE's and SAE's

    The number of patients who experience AE's and SAE's.

    Measured: Up to 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 posted17 Jun 2024
  2. Study start22 Jul 2024
  3. Primary completionJun 2027 (estimated)
  4. Study completionJun 2027 (estimated)

Why it stopped: funding issues

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06463184
Sponsor's protocol ID
MCC-22511
Status last verified
Dec 2024
First submitted
12 Jun 2024
Last updated
4 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Xevinapant in people with Recurrent High-grade Glioma, run by H. Lee Moffitt Cancer Center and Research Institute.

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 10 inclusion and 18 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: withdrawn, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

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 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.

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 withdrawn before enrolling participants, so there are no results.

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?

Concentration of Xevinapant (time frame: Within 48 hours of last dose of Xevinapant.). The study lists 2 primary outcomes in all. 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 NCT06463184.

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 4 Dec 2024.

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