Oral ONC201 in Adult Recurrent Glioblastoma and 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. Identifier: NCT02525692
Recruitment Status : Recruiting
First Posted : August 17, 2015
Last Update Posted : May 15, 2018
Information provided by (Responsible Party):
Oncoceutics, Inc.

Brief Summary:
ONC201 is a new drug candidate that kills cancer cells but not normal cells in laboratory studies and has been previously evaluated in a phase I clinical trial in advanced cancer patients. This clinical trial will enroll patients with recurrent glioblastoma or recurrent WHO Grade IV gliomas with the H3 K27M mutation.

Condition or disease Intervention/treatment Phase
Recurrent Glioblastoma Diffuse Midline Glioma H3 K27M Glioma Drug: ONC201 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Oral ONC201 in Adult Recurrent Glioblastoma and H3 K27M-mutant Glioma
Study Start Date : January 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: ONC201 (Q3W GBM) Drug: ONC201
Experimental: ONC201 (Q1W GBM) Drug: ONC201
Experimental: ONC201 (Q1W GBM Surgical) Drug: ONC201
Experimental: ONC201 (Q1W H3 K27M Glioma) Drug: ONC201
Experimental: ONC201 (Q1W H3 K27M Glioma Surgical) Drug: ONC201

Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: 6 months ]

Information from the National Library of Medicine

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

Inclusion Criteria:

For Arm A, B, and C: Histologically confirmed World Health Organization Grade IV glioblastoma. WHO Grade IV gliomas will be allowed on protocol.

For Arm D and E: WHO Grade IV glioma as per above and tumor must harbor a histone H3 K27M mutation as evidenced by testing any tumor sample with a immunohistochemistry or DNA sequencing test.

Unequivocal evidence of progressive disease on contrast-enhanced brain computerized tomography (CT) or magnetic resonance imaging (MRI) as defined by Response Assessment in Neuro-Oncology Criteria (RANO), or have documented recurrent glioblastoma on diagnostic biopsy.

Previous first line therapy with at least radiotherapy and temozolomide.

For Arm A: Any number of recurrences are allowable. For Arm B: First recurrence (only) glioblastoma who had a complete tumor resection at first diagnosis. For Arm C: Patients must have clinical and/or radiographic evidence of first recurrence of glioblastoma (only) and be eligible for salvage surgical resection as deemed by the site Investigator.

Must be 12 weeks from radiotherapy. If patients are within 12 weeks of radiotherapy, then the progressive lesion must be outside of the high-dose radiation target volume or have unequivocal evidence of progressive tumor on a biopsy specimen.

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.

All adverse events Grade > 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved, except for alopecia.

Male or Female age ≥18 years.

Karnofsky Performance Status (KPS) ≥ 60% (see Appendix A).

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 ≥ 100,000/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.

CT or MRI within 14 days prior to start of study drug.

Corticosteroid dose must be stable or decreasing for at least 5 days prior to the scan. For Arm B: Corticosteroid dose must be stable or decreasing for at least 2 weeks prior to study entry.

The effects of ONC201 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Male subjects should agree to use adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of therapy.

Archival tissue for evaluation of correlative objectives (if available). Archival tissue is required for Arms B and C.

Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients.

Current or planned participation in a study of an investigational agent or using an investigational device.

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.

Active infection requiring systemic therapy.

Prior stereotactic radiotherapy, convection enhanced delivery (CED) or brachytherapy must have had a biopsy to confirm radiographic progression is consistent with progressive tumor and not treatment-related necrosis. If the recurrent lesion is outside of any prior high-dose radiation target volume or distant from the prior CED or brachytherapy site, subjects will be considered eligible

Pregnant 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.

Known HIV-positive test on combination antiretroviral therapy.

Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias or bradycardia. 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.

Active illicit drug use or diagnosis of alcoholism.

Prior bevacizumab for treatment of glioblastoma. The rationale for restricting enrollment to patients who have not had prior bevacizumab therapy is that data regarding the efficacy of any therapy after progression on bevacizumab therapy are lacking.

Tumors with isocitrate dehydrogenase 1 (IDH1) or 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.

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 cervical cancer that has undergone potentially curative therapy.

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.

Concomitant use of CYP3A4/5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration.

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.

Planned concurrent use Optune™. Prior use of the device is allowable.

For Arm D: Evidence of leptomeningeal spread of disease.

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 identifier (NCT number): NCT02525692

United States, Florida
Miami Cancer Institute Recruiting
Miami, Florida, United States, 33176
Contact: Danieska Sandino   
Principal Investigator: Yazmin Odia, MD, MS         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Isabel Arrillaga, MD, PhD    617-726-2000   
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Patrick Wen, MD    617-632-2166   
Sponsors and Collaborators
Oncoceutics, Inc.

Responsible Party: Oncoceutics, Inc. Identifier: NCT02525692     History of Changes
Other Study ID Numbers: ONC006
First Posted: August 17, 2015    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018

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