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Trial record 3 of 5 for:    2OHOA

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04299191
Recruitment Status : Not yet recruiting
First Posted : March 6, 2020
Last Update Posted : March 6, 2020
Sponsor:
Collaborators:
Hackensack Meridian Health
Dana-Farber Cancer Institute
Laminar Pharma Inc
Information provided by (Responsible Party):
Laminar Pharmaceuticals

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 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.


Condition or disease Intervention/treatment Phase
High-grade Glioma Solid Tumor, Unspecified, Child Drug: 2-OHOA Phase 1 Phase 2

Detailed Description:

The dose of 2-OHOA each patient will receive will depend on the dose cohort into which they are enrolled.

Once a patient is allocated a dose of 2-OHOA (either in the dose escalation phase or the expanded safety cohort), it is planned that they will continue to receive the same dose on a daily basis in treatment cycles of 21 days (3 weeks), which may be repeated continuously without therapy interruption, until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion is met as defined in Section 5.5). In the event of significant gastrointestinal toxicity, the treatment schedule may be modified from continuous dosing to an intermittent regime (e.g. 1 week of dosing followed by 1 week not dosing), except during Cycle 1 of the dose escalation phase.

In the case of toxicity, the dose of 2-OHOA may be reduced or delayed by no more than 14 days at the discretion of the Investigator. Treatment "holidays" of no more than 14 days are also permitted for reasons other than toxicity, except during Cycle 1 of the dose escalation phase.

Intra-patient dose escalation may be permitted in certain specific circumstances (and only if ≤ Grade 2 toxicity was observed during previous treatment cycles), but toxicity will not be considered for definition of DLT.

It is expected that most patients will receive between one and 6 cycles of 2-OHOA for a treatment period of 3 to 18 weeks. The treatment period may be extended provided that no DLT has been observed and if in the opinion of the Investigator the patient is showing benefit from treatment with 2-OHOA.

Patients demonstrating clinical benefit from 2-OHOA will have the option of continuing treatment under compassionate use once the study has concluded.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Sequential Assignment
Intervention Model Description:

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.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study of 2-hydroxyoleic Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors
Estimated Study Start Date : March 2020
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation
The dose level corresponds to 80% of the maximum tolerated dose of 2-OHOA in adult patients when adjusted for body surface area. The escalation will be to the 100%, and 120% of the maximum tolerated dose of 2-OHOA 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 2-OHOA-related toxicities.
Drug: 2-OHOA

Once a patient is allocated a dose of 2-OHOA, 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 2-OHOA 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 2-OHOA.





Primary Outcome Measures :
  1. Safety and Tolerability of 2-OHOA [ Time Frame: Between 1 to 6 cycles (each cycle is 3 weeks) ]

    To determine the safety and tolerability of 2-OHOA 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].


  2. To identify the Recommended Phase 2 Dose (RP2D) of 2-OHOA in pediatric patients [ Time Frame: Between 1 to 6 cycles (each cycle is 3 weeks) ]
    The RP2D of 2-OHOA in pediatric patients will be the Maximum Tolerated Dose during the safety cohort and it's well tolerared.


Secondary Outcome Measures :
  1. Characterize 2-OHOA PK profile [ Time Frame: 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 2-OHOA dose) ]
    The maximum plasma drug concentration observed

  2. Characterize 2-OHOA PK profile [ Time Frame: 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 2-OHOA dose) ]
    The time at which the maximum plasma concentration is observed

  3. Characterize 2-OHOA PK profile [ Time Frame: 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 2-OHOA dose) ]
    The area under the plasma concentration versus time curve from time zero to the last quantifiable sampling point, AUC0-t, calculated by using the linear trapezoidal method

  4. Characterize 2-OHOA PK profile [ Time Frame: 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 2-OHOA dose) ]
    Accumulation ratio (R Cmax). Accumulation ratio calculated from Cmax after repeat dosing and Cmax after single dosing

  5. Characterize 2-OHOA PK profile [ Time Frame: 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 2-OHOA dose) ]
    Accumulation ratio (R AUC0-t) Accumulation ratio calculated from AUC(0-t) after repeat dosing and AUC(0-t) after single dosing

  6. To assess the preliminary anti-tumor efficacy of 2-OHOA [ Time Frame: Screening and every four cycles (12 weeks) ]
    Efficacy will be assessed by radiological response of the tumor to treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04299191


Contacts
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Contact: Adrian Gerald McNicholl +34971439886 a.mcnicholl@laminarpharma.com

Locations
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United States, New Jersey
Hackensack Meridian Health, Inc
Edison, New Jersey, United States, 08837
Contact: Derek Hanson, MD    155-199-6542    derek.hanson@hackensackmeridian.org   
Principal Investigator: Derek Hanson, MD         
Sponsors and Collaborators
Laminar Pharmaceuticals
Hackensack Meridian Health
Dana-Farber Cancer Institute
Laminar Pharma Inc
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Responsible Party: Laminar Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04299191    
Other Study ID Numbers: MIN-001P-1501
First Posted: March 6, 2020    Key Record Dates
Last Update Posted: March 6, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glioma
Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue