We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

ONC201 in Adults With Recurrent H3 K27M-mutant Glioma

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: NCT03295396
Recruitment Status : Recruiting
First Posted : September 27, 2017
Last Update Posted : March 8, 2018
Information provided by (Responsible Party):
Oncoceutics, Inc.

Brief Summary:
The primary objective of this phase II trial is to determine the efficacy and safety of ONC201, an oral small molecule imipridone DRD2 antagonist, in adult subjects with recurrent high-grade glioma. This study will test the research hypothesis that histone H3 K27M mutation sensitizes to oral administration of ONC201 in gliomas.

Condition or disease Intervention/treatment Phase
Glioma Drug: ONC201 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-label Study of ONC201 in Adults With Recurrent High-grade Glioma
Actual Study Start Date : October 31, 2017
Estimated Primary Completion Date : November 1, 2019
Estimated Study Completion Date : November 1, 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Intervention Details:
    Drug: ONC201
    ONC201 is an oral, small molecule selective antagonist of DRD2 that induces tumor cell death.

Primary Outcome Measures :
  1. Overall response rate [ Time Frame: Through study completion, an average of 1 year ]
    Best overall response rate by RANO

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.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically confirmed diagnosis of glioma (any histology, including but not limited to glioblastoma, astrocytoma, oligodendroglioma, malignant glioma, high-grade glioma, etc.) in any tumor sample and presence of histone H3 K27M mutation by a CLIA-approved immunohistochemistry or DNA sequencing test on any glioma tumor sample.
  2. Unequivocal evidence of progressive disease on contrast-enhanced brain CT or MRI as defined by RANO criteria, or have documented recurrent glioma on diagnostic biopsy.
  3. Measurable disease by RANO criteria.
  4. Patients can have had any number of prior therapies, however must have had previous therapy with at least radiotherapy.
  5. Interval of at least 8 weeks from the completion of radiotherapy. If patients are within 8 weeks of radiotherapy, they may still be eligible if they meet one or more of the following criteria.

    1. Progressive tumor is outside the original high-dose radiotherapy target volume as determined by the treating investigator, or
    2. Histologic confirmation of tumor through biopsy or resection, or
    3. Nuclear medicine imaging, MR spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than pseudoprogression or radiation necrosis obtained within 28 days of registration.
  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. 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.
  8. Male or Female age ≥18 years.
  9. Karnofsky Performance Status (KPS) ≥ 60.
  10. Adequate organ and marrow function as defined below, all screening labs should be performed within 14 days of treatment initiation:

    • leukocytes ≥ 3,000/mcL
    • absolute neutrophil count ≥ 1,500/mcL
    • platelets ≥ 75,000/mcL
    • hemoglobin > 8.0 mg/dL
    • total bilirubin ≤ 2.0 x upper limit of normal
    • AST (SGOT)/ALT (SGPT) ≤ 2.5 × upper limit of normal
    • creatinine OR creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above normal.
  11. Contrast-enhanced CT or MRI within 14 days prior to start of study drug.
  12. Corticosteroid dose must be stable or decreasing for at least 3 days prior to the baseline CT or MRI scan.
  13. The effects of ONC201 on the developing human fetus are unknown. For this reason, women of childbearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry and for the duration of study participation and for 30 days after the last dose of therapy. Highly effective contraceptive measures include: stable use of oral contraceptives such as combined estrogen and progestogen and progestogen only hormonal contraception or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; intrauterine hormone-releasing system (IUS); bilateral tubal ligation; vasectomy and sexual abstinence.

    1. WOCBP must have a negative serum or urine pregnancy test within 28 days of initiation of dosing.
    2. Contraception is not required for men with documented vasectomy.
    3. Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential.
    4. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
  14. Availability of a paraffin-embedded or frozen tumor-tissue block with a minimum of 1 cm2 of tumor surface area, or 20 unstained slides from the tumor tissue specimen if a tumor block cannot be submitted.
  15. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients.
  2. Current or planned participation in a study of an investigational agent or using an investigational device.
  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. Active infection requiring systemic therapy.
  5. Pregnant and/or breastfeeding women because ONC201 is novel agent with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ONC201, breastfeeding should be discontinued if the mother is treated with ONC201.
  6. Known HIV-positive test on combination antiretroviral therapy.
  7. Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias or bradycardia, unless arrhythmia is controlled and after Cardiology has cleared patient to receive ONC 201. 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.
  8. Active illicit drug use or diagnosis of alcoholism.
  9. Tumors with known IDH1 (isocitrate dehydrogenase 1) or known IDH2 mutations as determined by immunohistochemistry for the IDH1 R132H variant or by direct sequencing. IDH1/2-mutant gliomas have a markedly longer overall survival rate compared to those with IDH1/2-wildtype glioma (Parsons et al., 2008; Yan et al., 2009), indicating IDH1/2-mutant gliomas have a distinct natural history.
  10. Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ melanoma or in situ cervical cancer that has undergone potentially curative therapy.
  11. Any surgery (not including minor diagnostic procedures such as lymph node biopsy) within 2 weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures. An interval of 1 week for stereotactic brain biopsy from the start of study treatment is acceptable.
  12. Concomitant use of potent CYP3A4/5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration.
  13. Concomitant use of potent CYP3A4/5 inducers, which include enzyme inducing antiepileptic drugs (EIAEDs), during the treatment phase of the study and within 2 weeks prior to starting treatment.

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): NCT03295396

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

United States, New York
New York University School of Medicine Recruiting
New York, New York, United States, 10016
Contact: Amy Patel, RN    212-731-6267    amie.patel@nyumc.org   
Sponsors and Collaborators
Oncoceutics, Inc.

Responsible Party: Oncoceutics, Inc.
ClinicalTrials.gov Identifier: NCT03295396     History of Changes
Other Study ID Numbers: ONC013
First Posted: September 27, 2017    Key Record Dates
Last Update Posted: March 8, 2018
Last Verified: March 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:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue