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Glioma of BrainPhase 1/2GLIOMOONNCT03779230

Safety and Efficacy of L19TNF in Patients With Isocitrate Dehydrogenase (IDH) Wildtype WHO Grade III / IV Glioma at First Relapse

A Phase 1/2 study testing L19TNF in people with Glioma of Brain, run by Philogen S.p.A. at 3 sites in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Open label, non-randomized, mono-center Phase I/II study in subjects with IDH-wildtype WHO grade III / IV glioma at first relapse. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Glioma of Brain
What is being tested?
L19TNF
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
3 sitesSwitzerland
Study dates
31 May 2019to 27 Jun 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 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female, age 18 or more
  • Patients with histologically confirmed IDH-wildtype WHO grade III / IV glioma at first relapse
  • Radiographic demonstration of disease progression
  • Presence of at least one lesion of bi-dimensionally measurable disease by MRI of at least 1 cm (10 mm) in the longest diameter on baseline MRI.
  • Karnofsky Performance Score (KPS) ≥ 70%
  • Documented negative test for HIV-HBV-HCV. For HBV serology: the determination of HBsAg, anti-HBsAg-Ab and anti-HBcAg-Ab is required. In patients with serology documenting previous exposure to HBV (i.e., anti-HBs Ab with no history of vaccination and/or anti-HBc Ab), negative serum HBV-DNA is required. For HCV: HCV-RNA or HCV antibody test. Subjects with a positive test for HCV antibody but no detection of HCV-RNA indicating no current infection are eligible.
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  • Female patients: negative pregnancy test for women of childbearing potential (WOCBP)* within 14 days of starting treatment. WOCBP must agree to use, from the screening to six months following the last study drug administration, highly effective contraception methods, as defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group (www.hma.eu/ctfg.html) and which include, for instance, progesteron-only or combined (estrogen- and progesteron-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion or vasectomized partner.
  • Male patients: Male subjects able to father children must agree to use two acceptable methods of contraception throughout the study (e.g. condom with spermicidal gel). Double-barrier contraception is required.
  • Negative TB test (e.g. Mantoux or Quantiferon assay).
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
  • Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures *Women of childbearing potential are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy)

Who cannot join

  • Second or later glioma progression.
  • Surgical resection or biopsy of glioma within 4 weeks of the start of study treatment.
  • Subjects who participated in an investigational drug or device study within 4 weeks prior to study treatment start.
  • Treatment with tumor-treating fields
  • Radiotherapy within 6 weeks prior to study treatment start.
  • Patients unable to undergo contrast-enhanced MRI.
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  • Patient taking herbal medications within 7 days prior to first dose of the study drug.
  • Known history of allergy to TNF, excipient in study medication or any other intravenously administered human proteins/peptides/antibodies.
  • Absolute neutrophil count (ANC) < 1.5 x 10^9/L, platelets < 100 x 10^9/L or haemoglobin (Hb) < 9.0 g/dl.
  • Chronically impaired renal function as indicated by creatinine clearance < 60 mL/min.
  • Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 2.0 x ULN)
  • Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol, in the opinion of the investigator.
  • History within the last year of cerebrovascular disease and/or acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
  • Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).
  • Clinically significant cardiac arrhythmias or requiring permanent medication.
  • Abnormal LVEF or any other abnormalities observed during baseline ECG and echocardiogram investigations that are considered as clinically significant by the investigator.
  • Uncontrolled hypertension.
  • Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification).
  • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders.
  • Anxiety ≥ CTCAE grade 3
  • Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy.
  • Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 4 weeks of administration of study treatment.
  • Pregnancy or breast-feeding.
  • Requirement of chronic administration of high dose corticosteroids or other immunosuppressant drugs. Subjects must have been either off corticosteroids, or on a stable or decreasing dose ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to study treatment start. Limited or occasional use of corticosteroids to treat or prevent acute adverse reactions is not considered an exclusion criterion.
  • Presence of active and uncontrolled infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
  • Concurrent malignancies, unless the patient has been disease-free for at least 2 years.
  • Growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment.
  • Serious, non-healing wound, ulcer or bone fracture.
  • Requirement of concurrent therapy with anticoagulants at therapeutic doses.
  • Requirement of concurrent use of other anti-cancer treatments or agents other than study medication.
  • Any recent live vaccination within 4 weeks prior to treatment or plan to receive vaccination during the study.

Trial locations and contacts

3 sites in 1 country.

Switzerland3 sites

  • Inselspital Bern

    Bern, 3010

  • CHUV Départment d'Oncologie

    Lausanne, CH-1011

  • Universitatspital Zurich - Klinik fur Neurologie & Hirntumorzentrum

    Zurich, CH-8091

Other trials in Switzerland

About this study

Official title: A Study to Evaluate the Safety and Efficacy of the Tumor-targeting Human Antibody-cytokine Fusion Protein L19TNF in Patients With Isocitrate Dehydrogenase (IDH) Wildtype WHO Grade III / IV Glioma at First Relapse

Open label, non-randomized, mono-center Phase I/II study in subjects with IDH-wildtype WHO grade III / IV glioma at first relapse.

Read the detailed description

The purpose of this study is to explore the safety and efficacy profile of the antibody-cytokine fusion protein L19TNF in patients with isocitrate dehydrogenase (IDH) wildtype WHO grade III / IV glioma at first relapse

Phase I:

The primary objective of this phase is to evaluate the safety of L19TNF in patients with IDH-wildtype WHO grade III / IV glioma at first relapse and to establish and confirm the recommended dose (RD) for phase II.

Phase II:

The primary objective of this phase is to evaluate antitumor activity of L19TNF in patients with IDH-wildtype WHO grade III / IV glioma at first relapse.

Conditions
Glioma of Brain
Being tested
L19TNF

What participants receive

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

  • L19TNFDrug

    Also called onfekafusp alpha

    Patients will be assigned to the following increasing dose levels of L19TNF: 10 and 13 μg/kg.

Study groups in NCT03779230
Study groupRoleWhat they receive
L19TNFExperimentalPatients will be assigned to the following increasing dose levels of L19TNF: 10 and 13 μg/kg.
Receives: Drug: L19TNF

What is being measured

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

  1. Occurrence of Dose Limiting Toxicity (DLT)

    Measured: From the first day of treatment until the end of the DLT window (up to 21 days)

  2. Adverse event (AE), Serious Adverse Events (SAE) and Drug Induced Liver Injury (DILI) assessment based on CTCAE v.5.0

    Measured: From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

  3. Standard laboratory (haematology, biochemistry, liver and urine analysis) parameters

    Measured: From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

  4. Neurological assessment using the Neurologic assessment in Neuro-Oncology (NANO) scale

    Measurement of neurological function in neuro-oncology

    Measured: From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

  5. Karnofsky Performance Status

    Assessment through a questionnaire of symptom-related restriction of activity, self-sufficiency and self-determination

    Measured: From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

  6. Electrocardiogram (ECG) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment.

    Measured: From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

  7. Echocardiogram (ECHO) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment.

    Measured: From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

  8. Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19TNF.

    Measured: Cycle 1 day 1 - First Follow Up visit (up to approximately 9 months)

  9. Progression-free survival (PFS), according to iRANO (immunotherapy response assessment in neuro-oncology) criteria based on standardized MRI protocol

    Measured: At 6 months

Secondary outcomes (3)

  1. Progression free survival (PFS)

    Measured: From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 12 months)

  2. Overall survival (OS).

    Measured: From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

  3. Overall Response Rate (ORR, consisting of Complete and partial Response), based on iRANO criteria.

    Measured: At 12 weeks, 18 weeks, 24 weeks, 36 weeks, 48 weeks

Timeline

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

  1. First posted19 Dec 2018
  2. Study start31 May 2019
  3. Primary completion27 Jun 2023
  4. Study completion27 Jun 2023

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
Model description
Open label, non-randomized, mono-center Phase I/II study in subjects with IDH-wildtype WHO grade III / IV glioma at first relapse.
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03779230
Sponsor's protocol ID
PH-L19TNFGLIO-02/18
Acronym
GLIOMOON
Status last verified
Jun 2023
First submitted
14 Dec 2018
Last updated
29 Jun 2023
Results posted
No
Data monitoring committee
No
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 L19TNF in people with Glioma of Brain, run by Philogen S.p.A. at 3 sites in Switzerland.

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 11 inclusion and 31 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: finished, as of the sponsor's last update on 29 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Switzerland. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Occurrence of Dose Limiting Toxicity (DLT) (time frame: From the first day of treatment until the end of the DLT window (up to 21 days)). The study lists 9 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 NCT03779230.

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 29 Jun 2023.

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