GlioblastomaPhase 1GLIOASTRANCT05304663
Safety and Efficacy of Different Administration Sequences of L19TNF With Lomustine in Glioblastoma at First Progression
A Phase 1 study testing Onfekafusp alfa and Lomustine in people with Glioblastoma, run by Philogen S.p.A..
Trial summary
Open label phase I study in subjects with glioblastoma at first progression to explore two different administration schedules of lomustine for the combination with L19TNF (ARM 1 and ARM 2). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Onfekafusp alfa and Lomustine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2022to 31 Dec 2024
- 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, age ≥18.
- Patients with histologically confirmed glioblastoma per 2021 WHO classification at first progression according to RANO criteria. Imaging data on progression must be available. Resection as previous treatment for progression or recurrence is allowed.
- MGMT promotor methylation status known or tumor tissue for analysis available.
- Presence of at least one lesion of measurable disease of 10 x 10 mm in longest perpendicular diameters on baseline MRI according to RANO criteria.
- Karnofsky performance status (KPS) ≥ 60%.
- Documented negative test for HIV-HBV-HCV. For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV, negative serum HBV-DNA is required. For HCV, HCV-RNA or HCV antibody test is required. Subjects with a positive test for HCV antibody but no detection of HCV-RNA indicating no current infection are eligible.
Show all 11Show fewer
- Female patients: female patients must be either documented not Women Of Childbearing Potential (WOCBP)* or must have a negative pregnancy test within 14 days of starting treatment. Additionally WOCBP must agree to use, from the screening to 6 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, progesterone-only or combined (estrogen- and progesterone-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.
- 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
- Inability to undergo contrast-enhanced MRI.
- Prior treatment for glioblastoma at recurrence, except surgery.
- Surgical resection or biopsy of glioma within 4 weeks of the start of study treatment.
- Previous treatment with L19TNF.
- Known history of allergy to TNF or lomustine, any excipient in the 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.
Show all 31Show fewer
- Chronically impaired renal function as indicated by creatinine clearance < 60 mL/min or serum creatinine > 1.5 ULN.
- Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 2.0 x ULN).
- INR > 1.5 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.
- Active or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent, in the judgement 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.
- LVEF <55% or any other abnormalities observed during baseline ECG and echocardiogram investigations that are considered as clinically significant by the investigator. Subjects with current or a history of QT/QTc prolongation are excluded.
- Uncontrolled hypertension.
- Known arterial aneurism at high risk of rupture.
- Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification).
- 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 3 weeks of administration of study treatment.
- Known history of tuberculosis.
- 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 ≤ 4 mg daily dexamethasone (or equivalent) for 7 days prior to start of treatment. 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 without intervention 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 live vaccination during the study.
About this study
Official title: A Study to Evaluate the Safety and Efficacy of Different Administration Sequences of L19TNF in Combination With Lomustine in Patients With Glioblastoma at First Progression
Open label phase I study in subjects with glioblastoma at first progression to explore two different administration schedules of lomustine for the combination with L19TNF (ARM 1 and ARM 2).
Patients will be assigned in an alternating fashion to ARM 1 "Fractionating lomustine" or ARM 2 "Priming with L19TNF" as long as both treatment arms are open. Should one treatment arm be stopped as more or equal to two dose limiting toxicities occur in this treatment arm, then all remaining patients will be assigned to the treatment arm that is still open until also this treatment arm will be stopped.
- Conditions
- Glioblastoma
- Being tested
- Onfekafusp alfa, Lomustine
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Onfekafusp alfaDrug
Also called L19TNF
Patients will be treated with 10 µg/kg L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26
LomustineDrug
Arm 1: Patients will be treated in escalating cohorts of 6 patients with lomustine at different doses (60 mg/m2 and 75 mg/m2) on Day 1 and Day 22 (taken in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.
Arm 2: Patients will be treated in escalating cohorts of 6 patients with lomustine at different doses (90 mg/m2 and 110 mg/m2) on Day 5 (in the evening after infusion of L19TNF) of a 42-day cycle for up to a maximum of 6 cycles.
| Study group | Role | What they receive |
|---|---|---|
| ARM 1: Fractionating Lomustine | Experimental | Patients will be treated in escalating cohorts of 6 patients with 10 µg/kg L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and lomustine at different doses on Day 1 and Day 22 (taken in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.
* Cohort 1: 10 µg/kg L19TNF and 60 mg/m2 lomustine
* Cohort 2: 10 µg/kg L19TNF and 75 mg/m2 lomustine Receives: Drug: Onfekafusp alfa; Drug: Lomustine |
| ARM 2: Priming with L19TNF | Experimental | Patients will be treated in escalating cohorts of 6 patients with 10 µg/kg L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and lomustine at different doses on Day 5 (in the evening after infusion of L19TNF) of a 42-day cycle for up to a maximum of 6 cycles.
* Cohort 1: 10 µg/kg L19TNF and 90 mg/m2 lomustine
* Cohort 2: 10 µg/kg L19TNF and 110 mg/m2 lomustine In each arm, patients will be enrolled sequentially and no more than 2 patients will be treated in Cycle 1 in the same arm in parallel.
Recruitment to an arm will be stopped should ≥ 2 DLTs occur in a cohort. Receives: Drug: Onfekafusp alfa; Drug: Lomustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of L19TNF plus lomustine with different administration sequences
Occurrence of dose limiting toxicity (DLT) assessed by frequency and grade of adverse events (AE) according to CTCAE v.5.0.
Measured: From Day 1 to Day 42 of Cycle 1 (each cycle is 42 days)
Secondary outcomes (9)
ORR
Overall response rate
Measured: At 6 weeks, 12 weeks, 24 weeks and every 12 weeks up to 1 year
DCR
Disease control rate
Measured: At 6 weeks, 12 weeks, 24 weeks and every 12 weeks through study completion, an average of 1 year
PFS
Progression-free survival (PFS) based on iRANO criteria and a standardized MRI protocol
Measured: At 6 weeks, 12 weeks, 24 weeks and every 12 weeks through study completion, an average of 1 year
PFS at 6 months
Progression-free survival (PFS) rate at 6 months
Measured: At 6 months
OS
Overall survival (OS)
Measured: At 6 weeks, 12 weeks, 24 weeks and every 12 weeks through study completion, an average of 1 year
OS at 12 months
Overall survival (OS) rate at 12 months
Measured: At 12 months
Safety (AE)
Adverse events (AE) according to CTCAE v.5.0
Measured: Throughout the study: from the enrolment through study completion, an average of 1 year
Safety (SAE)
Serious adverse events (SAE) according to CTCAE v.5.0
Measured: Throughout the study: from the enrolment through study completion, an average of 1 year
Safety (DILI)
Drug induced liver injury (DILI) according to CTCAE v.5.0.
Measured: Throughout the study: from the enrolment through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2022
- Study start1 Jun 2022 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Why it stopped: The Sponsor had no further plan for the study in object
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Philogen S.p.A.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Open label phase I study in subjects with glioblastoma at first progression to explore two different administration schedules of lomustine for the combination with L19TNF (ARM 1 and ARM 2). Patients will be assigned in an alternating fashion to ARM 1 or ARM 2 as long as both treatment arms are open. Should one treatment arm be stopped as more or equal to two dose limiting toxicities occur in this treatment arm, then all remaining patients will be assigned to the treatment arm that is still open until also this treatment arm will be stopped.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Philogen S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05304663
- Sponsor's protocol ID
- PH-L19TNFLOM-05/21
- Acronym
- GLIOASTRA
- Status last verified
- Apr 2024
- First submitted
- 24 Feb 2022
- Last updated
- 8 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Safety and Efficacy of Different Administration Sequences of L19TNF in Combination With Lomustine in Patients With Glioblastoma at First Progression
- ClinicalTrials.gov ID
- NCT05304663
- Acronym / sponsor ID
- GLIOASTRA / PH-L19TNFLOM-05/21
- Conditions
- Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The Sponsor had no further plan for the study in object
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Philogen S.p.A.Industry (pharma, biotech, devices)
- Study start
- 1 Jun 2022 (estimated)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 31 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open label phase I study in subjects with glioblastoma at first progression to explore two different administration schedules of lomustine for the combination with L19TNF (ARM 1 and ARM 2).
Patients will be assigned in an alternating fashion to ARM 1 "Fractionating lomustine" or ARM 2 "Priming with L19TNF" as long as both treatment arms are open. Should one treatment arm be stopped as more or equal to two dose limiting toxicities occur in this treatment arm, then all remaining patients will be assigned to the treatment arm that is still open until also this treatment arm will be stopped.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open label phase I study in subjects with glioblastoma at first progression to explore two different administration schedules of lomustine for the combination with L19TNF (ARM 1 and ARM 2). Patients will be assigned in an alternating fashion to ARM 1 or ARM 2 as long as both treatment arms are open. Should one treatment arm be stopped as more or equal to two dose limiting toxicities occur in this treatment arm, then all remaining patients will be assigned to the treatment arm that is still open until also this treatment arm will be stopped.
| Arm | Type | Receives |
|---|---|---|
| ARM 1: Fractionating Lomustine | Experimental | Drug: Onfekafusp alfa, Drug: LomustinePatients will be treated in escalating cohorts of 6 patients with 10 µg/kg L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and lomustine at different doses on Day 1 and Day 22 (taken in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles. * Cohort 1: 10 µg/kg L19TNF and 60 mg/m2 lomustine * Cohort 2: 10 µg/kg L19TNF and 75 mg/m2 lomustine |
| ARM 2: Priming with L19TNF | Experimental | Drug: Onfekafusp alfa, Drug: LomustinePatients will be treated in escalating cohorts of 6 patients with 10 µg/kg L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and lomustine at different doses on Day 5 (in the evening after infusion of L19TNF) of a 42-day cycle for up to a maximum of 6 cycles. * Cohort 1: 10 µg/kg L19TNF and 90 mg/m2 lomustine * Cohort 2: 10 µg/kg L19TNF and 110 mg/m2 lomustine In each arm, patients will be enrolled sequentially and no more than 2 patients will be treated in Cycle 1 in the same arm in parallel. Recruitment to an arm will be stopped should ≥ 2 DLTs occur in a cohort. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female, age ≥18.
- Patients with histologically confirmed glioblastoma per 2021 WHO classification at first progression according to RANO criteria. Imaging data on progression must be available. Resection as previous treatment for progression or recurrence is allowed.
- MGMT promotor methylation status known or tumor tissue for analysis available.
- Presence of at least one lesion of measurable disease of 10 x 10 mm in longest perpendicular diameters on baseline MRI according to RANO criteria.
- Karnofsky performance status (KPS) ≥ 60%.
Key exclusion criteria (31 listed)
- Inability to undergo contrast-enhanced MRI.
- Prior treatment for glioblastoma at recurrence, except surgery.
- Surgical resection or biopsy of glioma within 4 weeks of the start of study treatment.
- Previous treatment with L19TNF.
- Known history of allergy to TNF or lomustine, any excipient in the study medication or any other intravenously administered human proteins/peptides/antibodies.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Onfekafusp alfaAlso: L19TNFPatients will be treated with 10 µg/kg L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 | Drug | ARM 1: Fractionating Lomustine, ARM 2: Priming with L19TNF |
| LomustineArm 1: Patients will be treated in escalating cohorts of 6 patients with lomustine at different doses (60 mg/m2 and 75 mg/m2) on Day 1 and Day 22 (taken in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles. Arm 2: Patients will be treated in escalating cohorts of 6 patients with lomustine at different doses (90 mg/m2 and 110 mg/m2) on Day 5 (in the evening after infusion of L19TNF) of a 42-day cycle for up to a maximum of 6 cycles. | Drug | ARM 1: Fractionating Lomustine, ARM 2: Priming with L19TNF |
Primary outcome
Safety of L19TNF plus lomustine with different administration sequences
Time frame: From Day 1 to Day 42 of Cycle 1 (each cycle is 42 days)
Occurrence of dose limiting toxicity (DLT) assessed by frequency and grade of adverse events (AE) according to CTCAE v.5.0.
9 secondary outcomes
ORR
Time frame: At 6 weeks, 12 weeks, 24 weeks and every 12 weeks up to 1 year
DCR
Time frame: At 6 weeks, 12 weeks, 24 weeks and every 12 weeks through study completion, an average of 1 year
PFS
Time frame: At 6 weeks, 12 weeks, 24 weeks and every 12 weeks through study completion, an average of 1 year
PFS at 6 months
Time frame: At 6 months
OS
Time frame: At 6 weeks, 12 weeks, 24 weeks and every 12 weeks through study completion, an average of 1 year
OS at 12 months
Time frame: At 12 months
Safety (AE)
Time frame: Throughout the study: from the enrolment through study completion, an average of 1 year
Safety (SAE)
Time frame: Throughout the study: from the enrolment through study completion, an average of 1 year
Safety (DILI)
Time frame: Throughout the study: from the enrolment through study completion, an average of 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2024.
- Individual participant dataSharing planned: No
Related trials for Glioblastoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Onfekafusp alfa and Lomustine in people with Glioblastoma, run by Philogen S.p.A..
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: withdrawn, as of the sponsor's last update on 8 Apr 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?
Safety of L19TNF plus lomustine with different administration sequences (time frame: From Day 1 to Day 42 of Cycle 1 (each cycle is 42 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Apr 2024.