Treatment of pediatric patients with advanced solid tumors using LAM561

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

This study is testing a new treatment called LAM561 for children with advanced solid tumors to see if it's safe and how well it works.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: N/A to 18 Years
• Sex: All
• Sponsor: Laminar Pharmaceuticals (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 3 sites (Little Rock, Arkansas and 2 other locations)
• Trial ID: NCT04299191 on ClinicalTrials.gov

What this trial studies

This clinical trial is an open-label, non-randomized study evaluating the safety and efficacy of LAM561 in pediatric patients with advanced high-grade gliomas and other solid tumors. The study consists of two phases: a dose escalation phase to determine the maximum tolerated dose (MTD) and an expanded safety cohort to further assess the safety of this dose. Patients will receive LAM561 daily in 21-day treatment cycles until disease progression or unacceptable toxicity occurs. The trial aims to establish a recommended phase 2 dose based on the findings from the initial cohorts.

Who should consider this trial

Good fit: Ideal candidates for this study are pediatric patients under 18 years old with advanced solid malignancies that are progressive, recurrent, or refractory to standard treatments.

Not a fit: Patients with tumors that have established effective standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for children with advanced solid tumors that currently have limited or no effective treatments.

How similar studies have performed: While this approach is novel for pediatric solid tumors, similar studies in adult populations have shown promising results with targeted therapies.

Eligibility criteria

Inclusion Criteria:

1. Age \<18 years
2. 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.
3. 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.
4. 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.
5. Able to swallow and ingest oral medication or have a NG or G-tube for drug administration
6. 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
7. 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.
8. Adequate Renal Function Defined As Either

   * Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2
   * or a serum creatinine less than or equal to the institutional normal for age
9. No history of QTc prolongation, and a normal QTc interval at screening/baseline (QTc ≤450 msec)
10. No evidence of a bleeding diathesis
11. Negative pregnancy test in women of childbearing potential within 7 days of initiating investigational therapy
12. Patient or legal guardian must give written, informed consent or assent (when applicable) -
13. Recent mothers must agree not to breast feed while receiving medications on study.

Exclusion Criteria:

1. Age ≥ 18 years
2. Known hypersensitivity to any component of the study drug
3. Use of any other investigational drug within five half-lives of that drug prior to the first dose of LAM561
4. 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
5. Any surgery within 14 days prior to the first dose of LAM561 (excluding shunt or line insertion)
6. 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
7. 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
8. 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)
9. Patients who are unable to take oral medications because of significant uncontrolled vomiting will be excluded.
10. A history of uncontrolled hyperlipidemia and/or the need for concurrent lipid lowering therapy
11. Concurrent severe and/or uncontrolled other medical disease (e.g. uncontrolled diabetes mellitus, active uncontrolled infection) that could compromise participation in the study
12. Need for warfarin, phenytoin or sulphonylureas (glibenclamide, glimepiride, glipizide,glyburide or nateglanide)
13. 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
14. Pregnant female patients are not eligible for this study. Pregnancy tests with a negative result must be obtained in all post-menarchal females.
15. Lactating females must agree they will not breastfeed a child while on this study.
16. Males and females of reproductive potential may not participate unless they agree to use an effective contraceptive method and continue to do so for at least 6 months after the completion of therapy.

Where this trial is running

Little Rock, Arkansas and 2 other locations

• Arkansas Children's Research Institute — Little Rock, Arkansas, United States (Recruiting)
• University of Miami Hospital — Miami, Florida, United States (Recruiting)
• Hackensack Meridian Health, Inc — Edison, New Jersey, United States (Recruiting)

Study contacts

• Study coordinator: Adrian Gerald McNicholl

Conditions High-grade Glioma; Solid Tumor, Unspecified, Child