Study of LAM561 Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors
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.
• 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.
• 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
• No history of QTc prolongation, and a normal QTc interval at screening/baseline (QTc ≤450 msec)
⁃ No evidence of a bleeding diathesis
⁃ Negative pregnancy test in women of childbearing potential within 7 days of initiating investigational therapy
⁃ Patient or legal guardian must give written, informed consent or assent (when applicable) -
⁃ Recent mothers must agree not to breast feed while receiving medications on study.