Study of LAM561 Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors
High-grade Glioma, Solid Tumor, Unspecified, Child
About this trial
This is an interventional treatment trial for High-grade Glioma
Eligibility Criteria
Inclusion Criteria:
- 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.
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.
Exclusion Criteria:
- Age ≥ 18 years
- Known hypersensitivity to any component of the study drug (see Section 6.1)
- Use of any other investigational drug within five half-lives of that drug prior to the first dose of 2-OHOA
- Anti-cancer therapy within 4 weeks prior to the first dose of 2-OHOA (6 weeks for mitomycin and nitrosureas, 4 weeks for curative-intent radiotherapy, and 2 weeks for palliative radiotherapy)
- 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 2-OHOA (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.
- 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.
Sites / Locations
- Hackensack Meridian Health, IncRecruiting
Arms of the Study
Arm 1
Experimental
Dose Escalation
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.