Primary GlioblastomaPhase 2/3CLINGLIONCT04250922
LAM561 With RT and TMZ for Adults With Glioblastoma
A Phase 2/3 study testing LAM561, TMZ and RT in people with Primary Glioblastoma and Glioblastoma Multiforme, run by Laminar Pharmaceuticals at 22 sites in 5 countries.
Trial summary
The proposed Phase IIB/III randomized, double-blind, placebo-controlled trial in subjects with newly diagnosed primary glioblastoma multiforme (ndGBM) aims to compare the efficacy and safety of LAM561 versus placebo, given with standard of care (SoC) therapy of radiation therapy plus temozolomide (TMZ), followed by an… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Glioblastoma, Glioblastoma Multiforme
- What is being tested?
- LAM561, TMZ and RT
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 144 participants
- Where
- 22 sitesin 5 countries
- Study dates
- 1 Dec 2019to 30 Nov 2026
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent, signed and dated
- Subjects who are able to understand and follow instructions during the trial
- Age ≥18 and ≤75
- Subjects with newly histologically confirmed intracranial malignant glioma (glioblastoma WHO Grade IV) that is IDH1 wildtype (local assessment) and who are scheduled to receive chemo-radiotherapy with temozolomide
- Ability to swallow and retain oral medication
- Centrally obtained MGMT promoter methylation status
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- Subjects who underwent total or partial / incomplete resection and with the appropriate quantity of tumour tissue releasable for eligibility
- Karnofsky Performance Score (KPS) > 50 %
- Female subjects with a childbearing potential must have a negative pregnancy test within one week before inclusion in the trial. Those female and male subjects admitted in the study must use a reliable method of contraception, for female subjects during the study period up until 32 days after last study treatment and for male subjects up until 92 days after last study administration.
- Women must be:
- Either of NOT childbearing potential: postmenopausal (≥ 60 years of age, or < 60 years of age and amenorrhoea for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression with follicle-stimulating hormone (FSH) above 40 U/L and oestradiol below 30 ng/L, or if taking tamoxifen or toremifene, and age < 60 years, then FSH and oestradiol in the postmenopausal range), permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy), or otherwise incapable of pregnancy
- Or of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; male partner sterilization (the vasectomized partner should be the sole partner for that subject).
- A man who is sexually active and has not had a vasectomy must agree to use a barrier method of birth control e.g., either condom or partner with occlusive cap (diaphragm or cervical/vault caps).
- Adequate bone marrow function including: Absolute neutrophil count (ANC) ≥1,500/mm^3 or ≥1.5 x 10^9/L; Platelets ≥ 100,000/mm3 or ≥100 x10^9/L; Haemoglobin ≥ 9 g/dL (may have been transfused).
- Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal range (ULN), an aspartate aminotransferase (AST), level ≤ 2.5 × ULN, and an alanine aminotransferase (ALT) level ≤ 2.5 × ULN or, for subjects with documented metastatic disease to the liver, AST and ALT levels ≤ 5 × ULN. Subjects with documented Gilbert disease are allowed if total bilirubin ≤ 3 x ULN
- Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula
Who cannot join
- Known hypersensitivity to any component of the investigational product.
- Any other investigational drug within the preceding 30 days. Prior, concomitant, or planned concomitant treatment with anti-neoplastic aim including (but not limited) to NovoTumor Treatment Fields (Novo TTF), bevacizumab, intratumoural or intracavitary anti-neoplastic therapy (e.g Gliadel wafers), or other experimental therapeutics intended to treat the tumour.
- Subjects who underwent "only biopsy" resection
- Anticancer therapy within 4 weeks of study entry (6 weeks for mitomycin and nitrosoureas)
- Other major surgery within the preceding 30 days
- Allergy, hypersensitivity or other intolerability to temozolomide and its excipients, patients with hypersensitivity to dacarbazine and patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
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- Unable to undergo MRI
- Presenting with diffuse midline gliomas or multifocal GBM (distant from the flare or contralateral) or rapid progression between early post-surgery MRI and pre-radiotherapy MRI
- Uncontrolled or significant cardiovascular disease
- A history of uncontrolled hyperlipidaemia and/or the need for concurrent lipid lowering therapy
- Need for warfarin, phenytoin or sulphonylureas (glibenclamide, glimepiride, glipizide, glyburide or nateglanide)
- Past medical history of uncontrolled clinically significant active or chronic gastrointestinal disorders (for example, Crohn's disease, celiac disease, untreated stomach ulcers, etc) and gastro-inflammatory pathologies
- Uncontrolled diabetes mellitus, with glycated haemoglobin (HbA1c) levels at the screening visit of ≥7.5%
- Cardiac disease, defined specifically as either
- Mean resting corrected QT interval (QTc) > 470 msec (for women) and > 450 ms (for men) obtained from 3 consecutive ECGs
- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (example, complete left bundle branch block, third degree heart block)
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for Torsades de Pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age
- Previous malignancies within the last three years other than ndGBM, except successfully treated squamous cell carcinoma of the skin, superficial bladder cancer, and in situ carcinoma of the cervix.
Trial locations and contacts
22 sites in 5 countries.
22 sites in 5 countries
Spain9 sites
Hospital Clinic
Barcelona, Barcelona
Hospital Vall d'Hebron
Barcelona, Barcelona
Hospital del Mar
Barcelona
Hospital Universitario Reina Sofía
Córdoba, Andalusia
Hospital Clínico San Carlos
Madrid, Madrid
Hospital Universitario 12 De Octubre
Madrid
Hospital Parc Tauli
Sabadell
Hospital Universitario Virgen del Rocío
Seville, Andalusia
Hospital Universitari i Politécnic La Fe.
Valencia, Valencia, 46026
France4 sites
Institut Cancerologie de L'Ouest (ICO)
Angers
Centre Eugène Marquis (CEM)
Rennes
Gustave Roussy University Hospital
Rennes
Institut universitaire du cancer
Toulouse
Italy4 sites
Istituto Nazionale Neurologico Carlo Besta
Milan
Istituto Oncologico Veneto IRCCS
Padova, Veneto, 35131
Istituto Nazionale Tumori "Regina Elena"
Roma
University of Turin
Turin
United Kingdom4 sites
University Hospitals Birmingham NHS Foundation Trust - New Queen Elizabeth Hospital
Birmingham
Cambridge university hospital
Cambridge
The Royal Marsden Hospital
London
Freeman Hospital's Northern Centre of Cancer Care
Newcastle, Newcastle Upon Tyne, NE7 7DN
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Adjuvant Trial in Newly Diagnosed Primary Glioblastoma Subjects to Assess the Efficacy and Safety of LAM561 in Combination With Radiotherapy and Temozolomide Standard of Care Treatment.
The proposed Phase IIB/III randomized, double-blind, placebo-controlled trial in subjects with newly diagnosed primary glioblastoma multiforme (ndGBM) aims to compare the efficacy and safety of LAM561 versus placebo, given with standard of care (SoC) therapy of radiation therapy plus temozolomide (TMZ), followed by an adjuvant treatment of 6 month period of TMZ and then LAM561 or placebo in monotherapy.
Read the detailed description
This is a randomized, double-blind, placebo-controlled, 2 parallel arms (1:1 ratio), adjuvant trial to assess the efficacy of LAM561 versus placebo in patients with newly diagnosed, IDH1 wildtype, GBM. In all arms, patients will receive the SoC and will be randomized to receive either placebo or LAM561 dose.
The study is planned to enrol 140 patients. The primary endpoints of the study are PFS (for CMA) and OS (for FMA) as assessed after observing at least 66 PFS events and at least 90 OS events, respectively. It is expected that the analysis for PFS will be performed 1-2 years earlier than the analysis for OS.
An IDMC (Independent Data Monitoring Committee) meeting took place to assess the trial's futility and safety data from the start of the trial until September 2023. The IDMC had open access to the data without blinding; after analysis IDMC concluded that there were no concerns that would necessitate stopping the study for ethical reasons or safety issues that could adversely affect patients due to taking the medication, so the study is continuing as normal with no changes.
After 45 events for PFS are observed, a formal interim analysis will be performed and the data reviewed by an Independent Data Monitoring Committee (IDMC) or may be activated by the IDMC 12 months after the inclusion of the last patient if follow up is sufficient to identify an overall PFS or OS significant deviation from the literature. After reviewing the interim results, the iDMC will make recommendations regarding: the sample size and the continuation of the trial overall.
Further, the sample size and events will be re-estimated to ensure that the statistical power is maintained given the estimated treatment effect at interim analysis. The events/sample size increase will be based on the considerations of the success probability.
For that purpose, based on the conditional power, the interim results will be classified into the following zones: favourable, unfavourable or promising.
If the interim results fall in the promising zone, then it is planned to increase the total number of events both for PFS and OS by up to 50%, with up to 99 events for PFS and up to 135 events for OS. The total sample size will also be increased to up to 210 patients to ensure the desired number of events within a realistic time. If the interim results are favourable or unfavourable, the study size will remain as initially planned with 66 events for PFS and 90 for OS, collected from 140 patients.
The IDMC committee experts met in February 2024 after 45 PFS events occurred in the trial. Unblinded medical and clinical statistical data from 103 patients were evaluated to assess the efficacy - progression free survival (tumour growth or clinical deterioration) - of LAM561. The IDMC confirmed that, at the current level of evidence, after evaluating the Conditional Power of the unblinded results, no futility has been identified and recommends continuation of the study without modification.
In November 2024, After reaching 66 PFS events as stated by protocol, the independent data monitoring committee (IDMC) analyzed the data and recommended: (1) Continue the trial without modifications until 90 OS events (overall survival), when the final analysis will be carried out, estimated for Q4 2026; (2) that the trial should not be stopped for reasons of safety or futility and (3) opening the study, that is, removing the blind. From that moment, patients, doctors and Laminar as sponsor are able to know if any patient received placebo or LAM561.
- Conditions
- Primary Glioblastoma, Glioblastoma Multiforme
- Being tested
- LAM561, TMZ, RT
- Keywords
- malignant
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LAM561Drug
Subjects in Arm B will receive orally LAM561 during the Chemoradiation Phase.
Subjects in Arm B will receive LAM561 orally during the Maintenance (Adjuvant) Phase. Patients will continue to be administered with LAM561/Placebo after cycle 6 of the monotherapy phase until end of study. Adjuvant treatment will be discontinued upon determination of tumour progression as defined by RANO criteria, unacceptable toxicity, or refusal to continue study treatment.
TMZDrug
TMZ will be administered at 75 mg/m2, orally, once daily, continuously from Day 1 of radiotherapy to the last day of radiation for a maximum of 49 days.
During the Maintenance (Adjuvant) Phase, all subjects will receive oral TMZ 150 - 200 mg/m2 once daily on Days 1 - 5 of each 28-day cycle for 6 cycles.
RTRadiation
During the Chemoradiation Phase, all subjects will undergo focal RT, with one treatment given daily 5 days per week over approximately 6 weeks (and no more than 7 weeks).
| Study group | Role | What they receive |
|---|---|---|
| Arm A: SoC + placebo for LAM561 | Placebo comparator | Chemoradiation Phase: all subjects undergo focal RT, with a treatment given 5 days per week over ~6 weeks (no more than 7 weeks). TMZ will be administered at 75 mg/m2 orally, once daily, continuously throughout the RT for a maximum of 49 days. Subjects in Arm A will receive placebo every day from Day 1 of week 3 to the end of this Phase.
The start of the first cycle during the Maintenance (Adjuvant) Phase will be scheduled ~28 days (and never more than 42 days) after the last day of chemoradiation. During the Maintenance Phase, subjects will receive oral TMZ 150-200 mg/m2 once daily on Days 1-5 of each 28-day cycle for 6 cycles.
Subjects in Arm A will receive placebo every day during the first 3 weeks of each 28-day cycle and until progression. Patients will continue with Placebo after cycle 6 of the monotherapy phase until end of study. Adjuvant treatment will be discontinued upon determination of tumour progression, unacceptable toxicity or refusal to continue study treatment. Receives: Drug: TMZ; Radiation: RT |
| Arm B: SoC + 12 g/day of LAM561 | Experimental | Chemoradiation Phase: all subjects undergo focal RT, with a treatment given 5 days per week over ~6 weeks (no more than 7 weeks). TMZ will be administered at 75 mg/m2 orally, once daily, continuously throughout the RT for a maximum of 49 days. Subjects in Arm B will receive LAM561 every day from Day 1 of week 3 to the end of this Phase.
The start of the first cycle during the Maintenance Phase will be scheduled ~28 days (and never more than 42 days) after the last day of chemoradiation. During the Maintenance Phase, subjects will receive oral TMZ 150-200 mg/m2 once daily on Days 1-5 of each 28-day cycle for 6 cycles.
Subjects in Arm B will receive LAM561 during the Maintenance Phase. Patients will continue to be administered with LAM561 after cycle 6 of the monotherapy phase until end of study. Adjuvant treatment will be discontinued upon determination of tumour progression, unacceptable toxicity or refusal to continue study treatment. Receives: Drug: LAM561; Drug: TMZ; Radiation: RT |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ.
To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ, as assessed by
- Progression Free Survival (PFS) using the Response Assessment in Neuro-Oncology (RANO) criteria
Measured: Assessed after observing at least 66 PFS events
To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ.
To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ, as assessed by
- Overall Survival (OS)
Measured: Assessed after observing at least 90 OS events
Secondary outcomes (8)
To evaluate measures of clinical response
Changes in neurological function, based on Neurologic Assessment in Neuro-Oncology (NANO) criteria
Measured: Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression
To evaluate additional measures of efficacy
Time to Progression (TTP) (as assessed using RANO criteria)
Measured: Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression
To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) parameters
Blood samples for determination of plasma concentrations of LAM561 in combination with RT and/or TMZ.
Maximum Plasma Concentration [Cmax]
Measured: At week 3 and 5 (day in both cases) of chemo-radiotherapy phase and at day 1 and 15 of cycle 1 of the maintenance phase
To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) parameters
Blood samples for determination of plasma concentrations of LAM561 in combination with RT and/or TMZ.
Lowest plasma concentration reached before the next dose is administered (Trough)
Measured: At week 3 and 5 (day in both cases) of chemo-radiotherapy phase and at day 1 and 15 of cycle 1 of the maintenance phase
To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) parameters
Blood samples for determination of plasma concentrations of LAM561 in combination with RT and/or TMZ.
Area Under the plasma concentration-time Curve (AUC)
Measured: At week 3 and 5 (day in both cases) of chemo-radiotherapy phase and at day 1 and 15 of cycle 1 of the maintenance phase
To evaluate Health-related Quality of Life (HRQoL)
HRQoL assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC-QLQ C30, version 3.0 and brain cancer specific QLQ-BN20.
The QLQ-C30 is a 30-item patient self-report questionnaire composed of both multi-item and single scales, including five functional scales (physical, role, emotional, social, and cognitive), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status/HRQoL scale, and six single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties). Subjects rate items on a four-point scale, with 1 as "not at all" and 4 as "very much". The QLQ-C30 was developed and validated for use in a cancer patient population, and its reliability and validity is highly consistent across different language-cultural groups.
Measured: Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression
To evaluate Health-related Quality of Life (HRQoL)
HRQoL assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC-QLQ C30, version 3.0 and brain cancer specific QLQ-BN20.
The QLQ-BN20 is a 20-item patient self-report questionnaire that was developed specifically as a module for subjects with brain cancer. It consists of four domain scores, including future uncertainty, visual disorder, motor dysfunction, and communication deficit, as well as seven individual symptom items (headache, seizures, drowsiness, hair loss, itching, difficulty with bladder control, and weakness of both legs). Subjects rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A retrospective validation study has been conducted confirming its psychometric validity.
Measured: Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression
To evaluate Health-related Quality of Life (HRQoL)
HRQoL assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC-QLQ C30, version 3.0 and brain cancer specific QLQ-BN20.
The EORTC QLQ-C30/BN20 as outlined in SoA. These assessments should be completed prior to study drug administration and any other study procedures being performed at these visits, and prior to discussing with the subject that their disease has progressed.
Measured: Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2020
- Study start1 Dec 2019
- Primary completion15 Jan 2026 (estimated)
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary GlioblastomaStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized, double-blind, placebo-controlled, 2 parallel arms (1:1), adjuvant trial to assess the efficacy of LAM561 vs placebo in patients with ndGBM. The 2 arms are: Arm A: SoC + placebo for LAM561; Arm B: SoC + 12g/day of LAM561 Treatment consists of 3 phases: 1. Chemoradiotherapy (6 to 7 weeks) * RT in daily fractions of 2Gy, 5 days per week (60Gy) * TMZ 75mg/m2 daily (maximum of 49 days) * Placebo or LAM561 for 4 weeks (from week 3 to week 6, both inclusive) -Washout period (4 weeks) 2. Maintenance (4-week cycles, maximum of 6 cycles) * Placebo/LAM561 daily in the first 3 weeks of each cycle, followed by 7 days washout * TMZ 150-200mg/m2 daily in the first 5 days of each cycle 3. Monotherapy: 4-week cycles until disease progression, unacceptable toxicity or lack of clinical benefit Placebo/LAM561 daily in the first 3 weeks of each cycle followed by 7 days washout
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laminar Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Laboratory Corporation of America, Northern Institute for Cancer Research, Newcastle, Theradis pharma, LIPODOM THERAPEUTICS
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04250922
- Sponsor's protocol ID
- MIN-003-1806
- Acronym
- CLINGLIO
- Status last verified
- Nov 2025
- First submitted
- 18 Jun 2019
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Adjuvant Trial in Newly Diagnosed Primary Glioblastoma Subjects to Assess the Efficacy and Safety of LAM561 in Combination With Radiotherapy and Temozolomide Standard of Care Treatment.
- ClinicalTrials.gov ID
- NCT04250922
- Acronym / sponsor ID
- CLINGLIO / MIN-003-1806
- Conditions
- Primary Glioblastoma, Glioblastoma Multiforme
- Keywords
- malignant
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 144 participants (actual)
- Lead sponsor
- Laminar PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Laboratory Corporation of America, Northern Institute for Cancer Research, Newcastle, Theradis pharma, LIPODOM THERAPEUTICS
- Study start
- 1 Dec 2019 (actual)
- Primary completion
- 15 Jan 2026 (estimated)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 31 Jan 2020 (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.
The proposed Phase IIB/III randomized, double-blind, placebo-controlled trial in subjects with newly diagnosed primary glioblastoma multiforme (ndGBM) aims to compare the efficacy and safety of LAM561 versus placebo, given with standard of care (SoC) therapy of radiation therapy plus temozolomide (TMZ), followed by an adjuvant treatment of 6 month period of TMZ and then LAM561 or placebo in monotherapy.
Detailed description
This is a randomized, double-blind, placebo-controlled, 2 parallel arms (1:1 ratio), adjuvant trial to assess the efficacy of LAM561 versus placebo in patients with newly diagnosed, IDH1 wildtype, GBM. In all arms, patients will receive the SoC and will be randomized to receive either placebo or LAM561 dose.
The study is planned to enrol 140 patients. The primary endpoints of the study are PFS (for CMA) and OS (for FMA) as assessed after observing at least 66 PFS events and at least 90 OS events, respectively. It is expected that the analysis for PFS will be performed 1-2 years earlier than the analysis for OS.
An IDMC (Independent Data Monitoring Committee) meeting took place to assess the trial's futility and safety data from the start of the trial until September 2023. The IDMC had open access to the data without blinding; after analysis IDMC concluded that there were no concerns that would necessitate stopping the study for ethical reasons or safety issues that could adversely affect patients due to taking the medication, so the study is continuing as normal with no changes.
After 45 events for PFS are observed, a formal interim analysis will be performed and the data reviewed by an Independent Data Monitoring Committee (IDMC) or may be activated by the IDMC 12 months after the inclusion of the last patient if follow up is sufficient to identify an overall PFS or OS significant deviation from the literature. After reviewing the interim results, the iDMC will make recommendations regarding: the sample size and the continuation of the trial overall.
Further, the sample size and events will be re-estimated to ensure that the statistical power is maintained given the estimated treatment effect at interim analysis. The events/sample size increase will be based on the considerations of the success probability.
For that purpose, based on the conditional power, the interim results will be classified into the following zones: favourable, unfavourable or promising.
If the interim results fall in the promising zone, then it is planned to increase the total number of events both for PFS and OS by up to 50%, with up to 99 events for PFS and up to 135 events for OS. The total sample size will also be increased to up to 210 patients to ensure the desired number of events within a realistic time. If the interim results are favourable or unfavourable, the study size will remain as initially planned with 66 events for PFS and 90 for OS, collected from 140 patients.
The IDMC committee experts met in February 2024 after 45 PFS events occurred in the trial. Unblinded medical and clinical statistical data from 103 patients were evaluated to assess the efficacy - progression free survival (tumour growth or clinical deterioration) - of LAM561. The IDMC confirmed that, at the current level of evidence, after evaluating the Conditional Power of the unblinded results, no futility has been identified and recommends continuation of the study without modification.
In November 2024, After reaching 66 PFS events as stated by protocol, the independent data monitoring committee (IDMC) analyzed the data and recommended: (1) Continue the trial without modifications until 90 OS events (overall survival), when the final analysis will be carried out, estimated for Q4 2026; (2) that the trial should not be stopped for reasons of safety or futility and (3) opening the study, that is, removing the blind. From that moment, patients, doctors and Laminar as sponsor are able to know if any patient received placebo or LAM561.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- This is a randomized, double-blind, placebo-controlled, 2 parallel arms (1:1), adjuvant trial to assess the efficacy of LAM561 vs placebo in patients with ndGBM. The 2 arms are: Arm A: SoC + placebo for LAM561; Arm B: SoC + 12g/day of LAM561 Treatment consists of 3 phases: 1. Chemoradiotherapy (6 to 7 weeks) * RT in daily fractions of 2Gy, 5 days per week (60Gy) * TMZ 75mg/m2 daily (maximum of 49 days) * Placebo or LAM561 for 4 weeks (from week 3 to week 6, both inclusive) -Washout period (4 weeks) 2. Maintenance (4-week cycles, maximum of 6 cycles) * Placebo/LAM561 daily in the first 3 weeks of each cycle, followed by 7 days washout * TMZ 150-200mg/m2 daily in the first 5 days of each cycle 3. Monotherapy: 4-week cycles until disease progression, unacceptable toxicity or lack of clinical benefit Placebo/LAM561 daily in the first 3 weeks of each cycle followed by 7 days washout
| Arm | Type | Receives |
|---|---|---|
| Arm A: SoC + placebo for LAM561 | Placebo comparator | Drug: TMZ, Radiation: RTChemoradiation Phase: all subjects undergo focal RT, with a treatment given 5 days per week over ~6 weeks (no more than 7 weeks). TMZ will be administered at 75 mg/m2 orally, once daily, continuously throughout the RT for a maximum of 49 days. Subjects in Arm A will receive placebo every day from Day 1 of week 3 to the end of this Phase. The start of the first cycle during the Maintenance (Adjuvant) Phase will be scheduled ~28 days (and never more than 42 days) after the last day of chemoradiation. During the Maintenance Phase, subjects will receive oral TMZ 150-200 mg/m2 once daily on Days 1-5 of each 28-day cycle for 6 cycles. Subjects in Arm A will receive placebo every day during the first 3 weeks of each 28-day cycle and until progression. Patients will continue with Placebo after cycle 6 of the monotherapy phase until end of study. Adjuvant treatment will be discontinued upon determination of tumour progression, unacceptable toxicity or refusal to continue study treatment. |
| Arm B: SoC + 12 g/day of LAM561 | Experimental | Drug: LAM561, Drug: TMZ, Radiation: RTChemoradiation Phase: all subjects undergo focal RT, with a treatment given 5 days per week over ~6 weeks (no more than 7 weeks). TMZ will be administered at 75 mg/m2 orally, once daily, continuously throughout the RT for a maximum of 49 days. Subjects in Arm B will receive LAM561 every day from Day 1 of week 3 to the end of this Phase. The start of the first cycle during the Maintenance Phase will be scheduled ~28 days (and never more than 42 days) after the last day of chemoradiation. During the Maintenance Phase, subjects will receive oral TMZ 150-200 mg/m2 once daily on Days 1-5 of each 28-day cycle for 6 cycles. Subjects in Arm B will receive LAM561 during the Maintenance Phase. Patients will continue to be administered with LAM561 after cycle 6 of the monotherapy phase until end of study. Adjuvant treatment will be discontinued upon determination of tumour progression, unacceptable toxicity or refusal to continue study treatment. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Written informed consent, signed and dated
- Subjects who are able to understand and follow instructions during the trial
- Age ≥18 and ≤75
- Subjects with newly histologically confirmed intracranial malignant glioma (glioblastoma WHO Grade IV) that is IDH1 wildtype (local assessment) and who are scheduled to receive chemo-radiotherapy with temozolomide
- Ability to swallow and retain oral medication
Key exclusion criteria (18 listed)
- Known hypersensitivity to any component of the investigational product.
- Any other investigational drug within the preceding 30 days. Prior, concomitant, or planned concomitant treatment with anti-neoplastic aim including (but not limited) to NovoTumor Treatment Fields (Novo TTF), bevacizumab, intratumoural or intracavitary anti-neoplastic therapy (e.g Gliadel wafers), or other experimental therapeutics intended to treat the tumour.
- Subjects who underwent "only biopsy" resection
- Anticancer therapy within 4 weeks of study entry (6 weeks for mitomycin and nitrosoureas)
- Other major surgery within the preceding 30 days
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 |
|---|---|---|
| LAM561Subjects in Arm B will receive orally LAM561 during the Chemoradiation Phase. Subjects in Arm B will receive LAM561 orally during the Maintenance (Adjuvant) Phase. Patients will continue to be administered with LAM561/Placebo after cycle 6 of the monotherapy phase until end of study. Adjuvant treatment will be discontinued upon determination of tumour progression as defined by RANO criteria, unacceptable toxicity, or refusal to continue study treatment. | Drug | Arm B: SoC + 12 g/day of LAM561 |
| TMZTMZ will be administered at 75 mg/m2, orally, once daily, continuously from Day 1 of radiotherapy to the last day of radiation for a maximum of 49 days. During the Maintenance (Adjuvant) Phase, all subjects will receive oral TMZ 150 - 200 mg/m2 once daily on Days 1 - 5 of each 28-day cycle for 6 cycles. | Drug | Arm A: SoC + placebo for LAM561, Arm B: SoC + 12 g/day of LAM561 |
| RTDuring the Chemoradiation Phase, all subjects will undergo focal RT, with one treatment given daily 5 days per week over approximately 6 weeks (and no more than 7 weeks). | Radiation | Arm A: SoC + placebo for LAM561, Arm B: SoC + 12 g/day of LAM561 |
Primary outcome
To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ.
Time frame: Assessed after observing at least 66 PFS events
To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ, as assessed by - Progression Free Survival (PFS) using the Response Assessment in Neuro-Oncology (RANO) criteria
To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ.
Time frame: Assessed after observing at least 90 OS events
To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ, as assessed by - Overall Survival (OS)
8 secondary outcomes
To evaluate measures of clinical response
Time frame: Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression
To evaluate additional measures of efficacy
Time frame: Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression
To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) parameters
Time frame: At week 3 and 5 (day in both cases) of chemo-radiotherapy phase and at day 1 and 15 of cycle 1 of the maintenance phase
To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) parameters
Time frame: At week 3 and 5 (day in both cases) of chemo-radiotherapy phase and at day 1 and 15 of cycle 1 of the maintenance phase
To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) parameters
Time frame: At week 3 and 5 (day in both cases) of chemo-radiotherapy phase and at day 1 and 15 of cycle 1 of the maintenance phase
To evaluate Health-related Quality of Life (HRQoL)
Time frame: Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression
To evaluate Health-related Quality of Life (HRQoL)
Time frame: Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression
To evaluate Health-related Quality of Life (HRQoL)
Time frame: Baseline and Post-baseline: day 1 of each odd cycle of maintenance/monotherapy phase and at progression
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Individual participant dataSharing planned: Undecided
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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.
22 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing LAM561, TMZ and RT in people with Primary Glioblastoma and Glioblastoma Multiforme, run by Laminar Pharmaceuticals at 22 sites in 5 countries.
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 16 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: under way, not looking for participants, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Spain, France, Italy, United Kingdom, Israel. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
To evaluate the efficacy of LAM561 in combination with the standard of care (SoC) treatment of radiotherapy (RT) and TMZ. (time frame: Assessed after observing at least 66 PFS events). 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?
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 20 Nov 2025.