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ONC201 in Pediatric H3 K27M Gliomas

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ClinicalTrials.gov Identifier: NCT03416530
Recruitment Status : Recruiting
First Posted : January 31, 2018
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Oncoceutics, Inc.

Brief Summary:
This is a multicenter, open-label, two arm, dose escalation, phase I study of oral ONC201 in pediatric patients with newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) and recurrent/refractory H3 K27M gliomas. Arm A will define the RP2D for single agent ONC201 in pediatric patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy. This will allow for recurrent patients and also patients who have not yet recurred, but have completed radiation and will inevitably recur based on prior clinical experience and the literature. Arm B will define the RP2D for ONC201 in combination with radiation in pediatric patients with newly diagnosed DIPG.

Condition or disease Intervention/treatment Phase
Diffuse Intrinsic Pontine Glioma Glioma, Malignant Drug: ONC201 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ONC201 in Newly Diagnosed Diffuse Intrinsic Pontine Glioma and Recurrent/Refractory Pediatric H3 K27M Gliomas
Actual Study Start Date : January 29, 2018
Estimated Primary Completion Date : January 24, 2020
Estimated Study Completion Date : July 24, 2020


Arm Intervention/treatment
Experimental: ONC201 in relapsed/refractory H3 K27M glioma
Pediatric patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent/refractory disease.
Drug: ONC201
ONC201 is a orally active, small molecule DRD2 antagonist that kills cancer cells but not normal cells.

Experimental: ONC201 in newly diagnosed DIPG
Pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. If H3 K27M status of tumor is unknown or archival tumor tissue is not available, then patients must agree to submit a post-mortem biopsy specimen.
Drug: ONC201
ONC201 is a orally active, small molecule DRD2 antagonist that kills cancer cells but not normal cells.




Primary Outcome Measures :
  1. RP2D [ Time Frame: 28 days ]
    Determination of recommended Phase 2 dose (RP2D) as a single agent or in combination with radiation



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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 2 to less than 19 years of age.
  2. Patient body weight must be above the minimum necessary for the patient to receive the ONC201 dose indicated for the currently enrolling dose level. The minimum body weight ranges from 10 to 35kg depending on the dose level.
  3. Arm A: Patients with glioma who are positive for the H3 K27M mutation (positive testing in CLIA laboratory) and have completed at least one line of prior therapy. Evidence of progression is not required so that ONC201 may be administered to patients in the maintenance setting or to patients with recurrent disease. Post-mortem biopsy is required if H3 K27M status of tumor is unknown and archival tumor tissue not available.

    Arm B: Patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible with or without histologic confirmation. Post-mortem biopsy is required if H3 K27M status of tumor is unknown and archival tumor tissue not available.

  4. Evaluable disease by RANO.
  5. Karnofsky ≥ 50 for patients ≥ 16 years of age, and Lansky ≥ 50 for patients < 16 years of age.
  6. From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.
  7. Adequate organ function defined as:

    Bone Marrow:

    • Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 and
    • Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).

    Renal Function:

    • Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70mL/min/1.73 m2 or normal serum creatinine based on age as shown below or GFR > 70ml/min/1.73m^2: Age < 5 years: 0.8 mg/dL maximum Age 5 to < 10 years: 1.0 mg/dL maximum Age 10 to < 15 years: 1.2 mg/dL maximum Age > 15 years: 1.5 mg/dL maximum

    Liver Function:

    • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age and
    • SGPT (ALT) ≤ 110 U/L and
    • Serum albumin ≥ 2 g/dL.

    Neurologic Function:

    • Patients with seizure disorder may be enrolled if seizure disorder is well controlled.
  8. Ability to understand a written informed consent document, and the willingness to sign it. Assent will be obtained when appropriate based on the subjects age.
  9. For Arm A: Patients can have had any number of prior therapies, however must have had previous therapy with at least radiotherapy. All adverse events Grade > 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved to grade 1 or baseline, except for alopecia and sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment, are acceptable. Patients must be at least 2 weeks from the completion of myelosuppressive chemotherapy and/or biologic agent and must be at least 6 weeks post hematopoetic stem cell rescue following myeloablative therapy.
  10. For patients post pubertal: Female patients must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator.
  11. Corticosteroid dose must be stable or decreasing for at least 3 days prior to the baseline MRI scan.
  12. Ability to be able to swallow and retain orally administered medication.
  13. Archival tumor specimen: All subjects in Arm A must submit at least 5 unstained slides from a tumor specimen that harbors H3 K27M mutation. For subjects in Arm B, at least 5 unstained slides must be submitted if archival tissue is available from the DIPG. If no archival tumor tissue is available, or if H3 K27M status of tumor is unknown, then subjects must agree to submit a post-mortem biopsy specimen.

Exclusion Criteria:

  1. Current or planned participation in a study of another investigational agent or using an investigational device.
  2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients.
  3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
  4. Any known clinically significant active infection including bacterial, fungal or viral including hepatitis B (HBV), hepatitis C (HCV) or any underlying disease or in the recent past which could compromise enrollment and safety of the patient.
  5. Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias or bradycardia, unless arrhythmia is controlled and after Cardiology has cleared patient to receive ONC201. Receiving therapeutic agents known to prolong QT interval will be excluded. History of CHF, or MI or stroke in the last 3 months will be excluded.
  6. Active illicit drug use or diagnosis of alcoholism.
  7. Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.
  8. Concomitant use of potent CYP3A4/5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration.
  9. Concomitant use of potent CYP3A4/5 inducers, which include enzyme inducing antiepileptic drugs (EIAEDs) (see Appendix B), during the treatment phase of the study and within 2 weeks prior to starting treatment. Concurrent dexamethasone is allowed.

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): NCT03416530


Contacts
Contact: Clinical Operations Oncoceutics 1-888-ONCORXS info@oncoceutics.com

Locations
United States, Florida
Miami Cancer Institute Recruiting
Miami, Florida, United States, 33176
Contact: Danieska Sandino       danieskas@baptisthealth.net   
Principal Investigator: Yazmin Odia, MD, MS         
United States, Michigan
University of Michigan Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Carl Koschmann, MD    734-936-9814    ckoschma@umich.edu   
Principal Investigator: Carl Koschmann, MD         
United States, New York
New York University Recruiting
New York, New York, United States, 10016
Contact: Sharon Gardner, MD    646-929-7870    Sharon.Gardner@nyumc.org   
Principal Investigator: Sharon Gardner, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Soumen Khatua, MD    713-792-2121    SKhatua@mdanderson.org   
Principal Investigator: Wafik Zaky, MD         
Principal Investigator: Soumen Kahtua, MD         
Sponsors and Collaborators
Oncoceutics, Inc.

Responsible Party: Oncoceutics, Inc.
ClinicalTrials.gov Identifier: NCT03416530     History of Changes
Other Study ID Numbers: ONC014
First Posted: January 31, 2018    Key Record Dates
Last Update Posted: July 20, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue