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

NCT04299191 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: MIN-001P-1501
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

High-grade Glioma; Solid Tumor, Unspecified, Child

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability of LAM561

  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 \[ECGs\].

  Between 1 to 6 cycles (each cycle is 3 weeks)

• To identify the Recommended Phase 2 Dose (RP2D) of LAM561 in pediatric patients

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

  Between 1 to 6 cycles (each cycle is 3 weeks)

Secondary Outcomes (6)

• Characterize LAM561 PK profile

  During cycles 1 (Days 1, 8 and 15) and 2 (Day 1) (each cycle is 3 weeks) and at the end of study visit (30 days of the last LAM561 dose)

• Characterize LAM561 PK profile

  During cycles 1 (Days 1, 8 and 15) and 2 (Day 1) (each cycle is 3 weeks) and at the end of study visit (30 days of the last LAM561 dose)

• Characterize LAM561 PK profile

  During cycles 1 (Days 1, 8 and 15) and 2 (Day 1) (each cycle is 3 weeks) and at the end of study visit (30 days of the last LAM561 dose)

• Characterize LAM561 PK profile

  During cycles 1 (Days 1, 8 and 15) and 2 (Day 1) (each cycle is 3 weeks) and at the end of study visit (30 days of the last LAM561 dose)

• Characterize LAM561 PK profile

  During cycles 1 (Days 1, 8 and 15) and 2 (Day 1) (each cycle is 3 weeks) and at the end of study visit (30 days of the last LAM561 dose)

Study Arms (1)

Dose Escalation

EXPERIMENTAL

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.

Drug: LAM561

Interventions

LAM561 DRUG

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.

Dose Escalation

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age \<18 years
• Diagnosis: Patients must have a histologically- or cytologically-confirmed advanced solid malignancy that is progressive, recurrent or refractory to standard-of-care treatment, or for which there is no standard therapy. Examples of tumors that lack a standard therapy include, but are not limited to, high-grade glioma, diffuse midline glioma, and diffuse intrinsic pontine glioma. For patients with a radiographic diagnosis of diffuse midline glioma or diffuse intrinsic pontine glioma, histologic or cytologic confirmation of their diagnosis is not required.
• Timing of therapy:
• Patients must be enrolled before treatment begins. Treatment must start within 14 days of study enrollment.
• All clinical and laboratory studies to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated in the eligibility section.
• Patients must have a Lansky or Karnofsky performance status score of ≥ 50%, corresponding to ECOG categories of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
• Able to swallow and ingest oral medication or have a NG or G-tube for drug administration
• Able to undergo adequate tumor imaging, via computerized tomography (CT) or magnetic resonance imaging (MRI) scans or any other standardized tumor assessment method based on tumor type (PET, MIBG, etc) to evaluate disease evolution
• Adequate hematologic, renal, liver function as demonstrated by laboratory values:
• ANC ≥ 1,000/ul
• Hemoglobin ≥8.0 gm/dl
• Platelet count ≥ 100,000/ul
• Adequate Liver Function Defined As
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and
• SGPT (ALT) \< 2.5 x upper limit of normal (ULN) for age.

You may not qualify if:

• Age ≥ 18 years
• Known hypersensitivity to any component of the study drug
• Use of any other investigational drug within five half-lives of that drug prior to the first dose of LAM561
• Any National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE version 4.0) \>Grade 1 toxicities from prior chemotherapy or radiotherapy that could impact on safety outcome assessment
• Any surgery within 14 days prior to the first dose of LAM561 (excluding shunt or line insertion)
• Known \>Grade 1 intracranial or intratumoral hemorrhage either by CT or MRI scan within the last 1 month. Patients with resolving hemorrhage changes, punctuate hemorrhage or hemosiderin may enter the study
• A history of significant or uncontrolled cardiovascular disease, including New York Heart Association Class III-IV heart failure, a left ventricular ejection fraction which is clinically significantly abnormal as measured by 2-dimensional (2-D) echocardiogram or Multi Gated Acquisition(MUGA) scan, unstable angina or myocardial infarction within the preceding 6 months
• Known impairment of gastrointestinal (GI) function that could alter the absorption of study drug (e.g. active Crohn's disease, malabsorption syndrome or states, unresolved diarrhea, small bowel resection or gastric by-pass surgery)
• Patients who are unable to take oral medications because of significant uncontrolled vomiting will be excluded.
• A history of uncontrolled hyperlipidemia and/or the need for concurrent lipid lowering therapy
• Concurrent severe and/or uncontrolled other medical disease (e.g. uncontrolled diabetes mellitus, active uncontrolled infection) that could compromise participation in the study
• Need for warfarin, phenytoin or sulphonylureas (glibenclamide, glimepiride, glipizide,glyburide or nateglanide)
• Any serious and/or unstable pre-existing medical, psychiatric or other condition which in the Investigator's opinion could interfere with subject safety, obtaining written informed consent, or compliance with the study protocol
• Pregnant female patients are not eligible for this study. Pregnancy tests with a negative result must be obtained in all post-menarchal females.
• Lactating females must agree they will not breastfeed a child while on this study.

Sponsors & Collaborators

• Laminar Pharmaceuticals: lead
• Hackensack Meridian Health: collaborator
• Dana-Farber Cancer Institute: collaborator
• Laminar Pharma Inc: collaborator

Study Sites (3)

Arkansas Children's Research Institute

Little Rock, Arkansas, 72202, United States

RECRUITING

University of Miami Hospital

Miami, Florida, 33146, United States

RECRUITING

Hackensack Meridian Health, Inc

Edison, New Jersey, 08837, United States

RECRUITING

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Adrian Gerald McNicholl

CONTACT

+34971439886; clinical.dev@laminarpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: March 6, 2020
• Study Start: September 1, 2020
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 20, 2025

Record last verified: 2025-11

Locations

US (3)