Neoplasms

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Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

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.

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.

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.

LAM561

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.

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).

Adrian Gerald McNicholl

Elodie Vauleon, Dr.

Frederic Dhermain, Dr.

Elizabeth Cohen-Jonathan Moyal, Dr.

Giuseppe Lombardi, Dr.

Francesco DiMeco Dr.

Veronica Villani, Dr.

Riccardo Soffietti Dr.

Sonia García, Dr.

Miriam Alonso, Dr.

Regina Gironés Dr.

Estela Pineda, Dr.

Maria Martinez Dr.

Maria Vieito, Dr.

Pedro Pérez Segura, Dr.

Juan Manuel Sepulveda-Sanchez, Dr.

Júlia Giner, Dr.

Joanne Lewis, Dr.

Helen Benghiat, Dr.

Harris Fiona, Dr.

Liam Welsh, Dr.

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.

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.

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

At the Screening Visit, the IRT will assign a unique number to the subject. The site will use the IRT to receive drug kit numbers and a unique randomization number.

Subjects will be randomized to Arm A or B in a 1:1 ratio. Drug kit numbers and treatment content will be assigned according to a list generated before the start of the study. At interim, the IRT vendor will transfer the list of attribution to the iSCs. After the final lock, the list of attribution will be transmitted to the company involved in analysis. The IRT vendor will be in charge of the stock management/logistics in each site and shipments. Upon receipt of study drug, the study site will acknowledge receipt in the IRT system.

The investigators, the study site personnel and subject will remain blinded to throughout the course of the study. The IRT will provide access to for a subject in case of medical emergency. If sponsor/clinical team should break the blind, the reason will be documented on the eCRF.

LAM561 With RT and TMZ for Adults With Glioblastoma

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.

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, as assessed by

- Overall Survival (OS)

Changes in neurological function, based on Neurologic Assessment in Neuro-Oncology (NANO) criteria

Time to Progression (TTP) (as assessed using RANO criteria)

Blood samples for determination of plasma concentrations of LAM561 in combination with RT and/or TMZ.

Maximum Plasma Concentration \[Cmax\]

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)

Blood samples for determination of plasma concentrations of LAM561 in combination with RT and/or TMZ.

Area Under the plasma concentration-time Curve (AUC)

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.

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.

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.

Laboratory Corporation of America

Northern Institute for Cancer Research, Newcastle

Theradis pharma

LIPODOM THERAPEUTICS

Laminar Pharmaceuticals

The dose level corresponds to 80% of the maximum tolerated dose of LAM561 in adult patients when adjusted for body surface area. The escalation will be to the 100%, and 120% of the maximum tolerated dose of LAM561 in adult patients when adjusted for body surface area. Dose escalation decisions will be made by all active Investigators in collaboration with the Medical Monitor when at least three patients have completed the DLT observation period (Cycle 1) at each dose level. When the third patient at any given dose level has received 14 days of therapy, an "escalation teleconference" will be scheduled after that patient has completed the DLT observation period (Cycle 1). The decision to progress to the next dose level will be made on the basis of review of all significant LAM561-related toxicities.

Once a patient is allocated a dose of LAM561, they will receive the same dose on a daily basis in treatment cycles of 21 days (3 weeks), which may be repeated without therapy interruption until a criterion for discontinuation (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" criterion) is met.

The starting dose will be 2.8 g/m2 twice daily. If tolerated, doses will be escalated to 3.5 g/m2 twice daily and then to a third dose level of 4.2 g/m2 twice daily. These dose levels correspond to 80%, 100%, and 120% of the maximum tolerated dose of LAM561 in adult patients when adjusted for body surface area. A total of 3 dose cohorts are anticipated for the dose escalation phase of the study, with up to 6 patients enrolled at each dose level according to a standard "3+3" design. During each dose cohort, at least 1 week must elapse between the first and subsequent patients receiving treatment with LAM561.

Kevin Bielamowicz, MD

Derek Hanson, MD

An open label, non-randomized study in pediatric patients with advanced high-grade gliomas and other solid tumors.

The study will be performed in two phases: a dose escalation phase in up to 18 patients following a standard "3+3" design to establish dose-limiting toxicity (DLT) and a "safe" dose of LAM561 followed by an expanded safety cohort of up to 10 patients treated at the Maximum Tolerated Dose (MTD). If the MTD is well tolerated in the expanded safety cohort, that dose becomes the Recommended Phase 2 Dose (RP2D).

Glioma patients and other solid tumor patients (including non-glial brain tumors) will be treated as a single cohort. Patients with either tumor type will be allowed to enroll on the study as positions are made available. No tumor type will be given priority over another and there is no minimum number of glioma patients or solid tumor patients that must be enrolled on the trial.

The dose of LAM561 each patient will receive will depend on the dose cohort into which they are enrolled.

Once a patient is allocated a dose of LAM561 (either in the dose escalation phase or the expanded safety cohort), it is planned that they will continue to receive the same dose on a daily basis in treatment cycles of 21 days (3 weeks), which may be repeated continuously without therapy interruption, until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion is met as defined in Section 5.5). In the event of significant gastrointestinal toxicity, the treatment schedule may be modified from continuous dosing to an intermittent regime (e.g. 1 week of dosing followed by 1 week not dosing), except during Cycle 1 of the dose escalation phase.

In the case of toxicity, the dose of LAM561 may be reduced or delayed by no more than 14 days at the discretion of the Investigator. Treatment "holidays" of no more than 14 days are also permitted for reasons other than toxicity, except during Cycle 1 of the dose escalation phase.

Intra-patient dose escalation may be permitted in certain specific circumstances (and only if ≤ Grade 2 toxicity was observed during previous treatment cycles), but toxicity will not be considered for definition of DLT.

It is expected that most patients will receive between one and 6 cycles of LAM561 for a treatment period of 3 to 18 weeks. The treatment period may be extended provided that no DLT has been observed and if in the opinion of the Investigator the patient is showing benefit from treatment with LAM561.

Patients demonstrating clinical benefit from LAM561 will have the option of continuing treatment under compassionate use once the study has concluded.

Study of LAM561 Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors

To determine the safety and tolerability of LAM561 in pediatric patients (under 18 years) when administered orally using a continuous dosing schedule.

It will be evaluated through the adverse events \[AEs\], physical examinations and vital signs, laboratory safety tests and 12-lead electrocardiograms \[ECGs\].

The RP2D of LAM561 in pediatric patients will be the Maximum Tolerated Dose during the safety cohort and it's well tolerared.

The maximum plasma drug concentration observed

The time at which the maximum plasma concentration is observed

The area under the plasma concentration versus time curve from time zero to the last quantifiable sampling point, AUC0-t, calculated by using the linear trapezoidal method

Accumulation ratio (R Cmax). Accumulation ratio calculated from Cmax after repeat dosing and Cmax after single dosing

Accumulation ratio (R AUC0-t) Accumulation ratio calculated from AUC(0-t) after repeat dosing and AUC(0-t) after single dosing

Efficacy will be assessed by radiological response of the tumor to treatment

Hackensack Meridian Health

Dana-Farber Cancer Institute

Laminar Pharma Inc

Intervention: LAM561. 7 dose cohorts of up to 6 patients have been performed in the dose escalation phase. The starting dose cohort received 250 mg twice daily.

Intervention: LAM561. 4g three times daily

Intervention: LAM561 at the MTD: 4g three times daily. Up to 10 patients with malignant glioma.

Intervention: LAM561 at the MTD: 4g three times daily. Up to 10 patients with other advanced solid tumours that are suitable for biopsy.

Patients will receive treatment cycles of 21 days, until any criterion for discontinuation (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion) is met.

Patients are expected to receive between one and 6 cycles of treatment. The treatment period may be extended if clinical benefit is shown.

In the event of significant GI toxicity, the treatment schedule may be modified from continuous dosing to an intermittent regime In the case of toxicity, the dose of LAM561 may be reduced or delayed by up to 14 days at the discretion of the Investigator. A maximum of two dose reductions will be permitted per patient. Treatment "holidays" of no more than 14 days are also permitted for reasons other than toxicity. Intra-patient dose escalation may be permitted in certain specific circumstances.

Professor Johann de Bono, MB ChB FRCP MSc PhD

Prof. Ruth Plummer, BMBCh, MRCP, Cert Me

Dr Jordi Rodon

Dr Juanita Lopez

Dr Ricardo Fernandez Rodriguez

Dr Ander Urruticoechea Ribate

This is a phase 1/2A, open label, non-randomized study in patients with advanced solid tumours including malignant glioma

This is an open label, non-randomized study in patients with advanced solid tumours including malignant glioma. The study will be performed in two phases - a dose escalation phase following a standard "3+3" design to establish dose-limiting toxicity (DLT) and a safe dose of LAM561 followed by two expanded safety cohorts (approximately 10 of whom have malignant glioma and approximately 10 of whom have other advanced solid tumours that are suitable for biopsy) treated at the maximum tolerated dose (MTD). If the MTD is well tolerated in the expanded safety cohorts, that dose becomes the recommended phase 2 dose (RP2D). During each dose cohort, at least one week must elapse between the first and subsequent patients receiving treatment with LAM561. Patients may receive palliative localized radiotherapy, if needed (however, this lesion cannot be a target lesion for evaluation of the treatment response).

Safety, pharmacokinetics (PK), pharmacodynamics and efficacy will be evaluated during the study at pre-defined timepoints

A Phase 1/2A Study of LAM561 in Adult Patients With Advanced Solid Tumours

A Phase 1/2A Dose Escalation Study of LAM561 in Adult Patients With Advanced Solid Tumours Including Malignant Glioma

All adverse events will be recorded including clinically significant physical examinations and vital signs, laboratory safety tests and 12-lead electrocardiograms

Full profiles on Day 1 and Day 21 (dose escalation phase only), trough measurements on Day 8, 15 and 21

Effect on glial fibrillary acidic protein in glioma patients and effect on sphingomyelin and dihydrofolate reductase in patients with other solid tumours

Blood samples for future analysis of micro RNA

Measurement by CT or MRI scan. Changes scored according to Response Assessment in Neuro-oncology (RANO) criteria (for glioma patients) or Response evaluation criteria in solid tumours (RECIST v1.1) (for other solid tumour patients).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
LAM561 With RT and TMZ for Adults With Glioblastoma	NCT04250922	Primary Gliobla... Glioblastoma Mu...	LAM561 TMZ RT	18 Years - 75 Years	Laminar Pharmaceuticals
Study of LAM561 Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors	NCT04299191	High-grade Glio... Solid Tumor, Un...	LAM561	- 18 Years	Laminar Pharmaceuticals
A Phase 1/2A Study of LAM561 in Adult Patients With Advanced Solid Tumours	NCT01792310	Glioma Other Solid Tum...	LAM561	18 Years -	Laminar Pharmaceuticals
LAM561 With RT and TMZ for Adults With Glioblastoma	NCT04250922	Primary Gliobla... Glioblastoma Mu...	LAM561 TMZ RT	18 Years - 75 Years	Laminar Pharmaceuticals
LAM561 With RT and TMZ for Adults With Glioblastoma	NCT04250922	Primary Gliobla... Glioblastoma Mu...	LAM561 TMZ RT	18 Years - 75 Years	Laminar Pharmaceuticals

Spots Global Cancer Trial Database for lam561

Every month we try and update this database with for lam561 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lam561

Every month we try and update this database with for lam561 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lam561 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.