Study of 2-hydroxyoleic Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors

• Status: Recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

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 2-OHOA 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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Laminar Pharmaceuticals
• Collaborators: Dana-Farber Cancer Institute; Hackensack Meridian Health; Laminar Pharma Inc

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.

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 (see Section 6.1)

3. Use of any other investigational drug within five half-lives of that drug prior to the first dose of 2-OHOA

4. 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)

5. 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

6. Any surgery within 14 days prior to the first dose of 2-OHOA (excluding shunt or line insertion)

7. 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

8. 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

9. 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)

10. Patients who are unable to take oral medications because of significant uncontrolled vomiting will be excluded.

11. A history of uncontrolled hyperlipidemia and/or the need for concurrent lipid lowering therapy

12. Concurrent severe and/or uncontrolled other medical disease (e.g. uncontrolled diabetes mellitus, active uncontrolled infection) that could compromise participation in the study

13. Need for warfarin, phenytoin or sulphonylureas (glibenclamide, glimepiride, glipizide,glyburide or nateglanide)

14. 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

15. Pregnant female patients are not eligible for this study. Pregnancy tests with a negative result must be obtained in all post-menarchal females.

16. Lactating females must agree they will not breastfeed a child while on this study.

17. 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.