NCT04299191

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Sponsor: Laminar Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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. The first cohort of patients has been concluded, and a DSMB meeting was held on 03 April 2023 to assess the safety information in order to initiate the second cohort. The DSMB concluded the safety findings were supportive of initiation of the second cohort, and the second cohort was initiated. This second cohort has been concluded and another meeting of the DSMB was held on 17 January 2025 to review the safety information and concluded to commence the third cohort of patients with a new dose of idroxioleic acid (2-OHOA).

Conditions

• High-grade Glioma
• Solid Tumor, Unspecified, Child

Interventions

Type	Name	Description
DRUG	LAM561	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.

Timeline

• Start date: 2020-09-01
• Primary completion: 2026-10-01
• Completion: 2026-12-01
• First posted: 2020-03-06
• Last updated: 2025-11-20

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study