Recruiting PHASE1 Central Nervous System Neoplasms

New treatment option for Central Nervous System Neoplasms

Official title Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms

ClinicalTrials.gov ID: NCT04541082

What this study is testing

What is ONC206?

ONC206 is an investigational medicine, given as an once-weekly pill taken by mouth, being studied as a potential treatment for central nervous system neoplasms.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: The primary objective of this Phase 1, open-label, dose-escalation, and exploratory study is to evaluate the safety and tolerability profile (establish the maximum-tolerated dose) and evaluate the occurrence of dose-limiting toxicities (DLTs) following single weekly or multiple-day weekly dose regimens of single-agent, oral ONC206 in patients with recurrent, primary central nervous system (CNS) neoplasms.

Phase 1: an early, usually small safety study
You might receive a placebo (an inactive treatment) instead of the study drug. You may not know which one you got.

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 and older

You may be able to join if

Patients must meet all the following criteria to participate in the study:
Patients aged ≥18 years with a recurrent, primary CNS neoplasm. For all cohorts, patients must have a histologically confirmed primary CNS neoplasm...
Patients must have recurrent and measurable disease as defined by RANO criteria, using either the HGG and/or LGG RANO criteria based on tumor type...
Patients must have a Karnofsky Performance Score (KPS) of greater than or equal to 70. Patients with severe paraparesis/paraplegia who need minimal...
(Inclusion Criterion #4 was removed in Amendment 3.)

You likely can't join if

Patients who meet any of the following criteria will be excluded from the study:
(Exclusion Criterion #1 was removed in Amendment 3)
Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC206 (e.g., ONC201) or its...
Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations...
Patients who are unable or unwilling to abide by the study protocol or cooperate fully with the Investigator.
Patients with a known HIV-positive test on combination anti-retroviral therapy are ineligible for this initial first-in-human trial because of the...

See the full eligibility criteria

Who can join

Patients must meet all the following criteria to participate in the study:
Patients aged ≥18 years with a recurrent, primary CNS neoplasm. For all cohorts, patients must have a histologically confirmed primary CNS neoplasm. Primary CNS neoplasms in this study include, but are not limited to...
Patients must have recurrent and measurable disease as defined by RANO criteria, using either the HGG and/or LGG RANO criteria based on tumor type, after having received established standard of care treatment for their...
Patients must have a Karnofsky Performance Score (KPS) of greater than or equal to 70. Patients with severe paraparesis/paraplegia who need minimal assistance for self-care due to their motor deficit but are otherwise...
(Inclusion Criterion #4 was removed in Amendment 3.)
Patients must not have received prior investigational or approved cytotoxic chemotherapy within 28 days prior to the first dose of study drug (Cycle 1, Day 1); 42 days in the case of nitrosoureas; 42 days in the case of...
(Inclusion Criterion #6 was removed in Amendment 7.)
Patients with AEs Grade ≥2 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must have all their AEs resolved prior to the first dose of study drug (Cycle 1, Day 1), except for alopecia or...
Patients must not have undergone major surgery 4 weeks prior to the first dose of study drug (Cycle 1, Day 1) and must have completely recovered from any surgery (minor surgical procedures such as skin biopsies and port...
Patients must have normal organ and marrow function as defined below:
Absolute neutrophil count (ANC) ≥1,500/mcL.
Platelets ≥100,000/mcL.
Hemoglobin ≥9.0 mg/dL without transfusion in 2 prior weeks.
Total bilirubin ≤1.5 × upper limit of normal (ULN) (patients with Gilbert's syndrome may be included with total bilirubin \>1.5 × ULN if direct bilirubin is ≤1.5 × ULN).
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5 × ULN.
Measured or estimated creatinine clearance (CLcr) ≥40 mL/minute for patients with creatinine levels above normal. CLcr will be calculated by the Cockcroft-Gault equation for renal function.
(Inclusion Criterion #10 was removed in Amendment 3)
Patients must provide a tumor specimen (paraffin-embedded block and/or frozen tissue) from a prior resection or biopsy available that is sufficient to perform biomarker assays, ≥15 unstained slides for...
Dependent upon dose level assignment and drug formulation (i.e., capsules versus powder in bottle [PIB]), patients must be able to either swallow oral capsules or swallow liquids.
Patients must provide study-specific informed consent prior to enrollment. No Durable Power of Attorney or Next of Kin can provide initial consent.
Patients must be able to tolerate a magnetic resonance imaging (MRI) study with intravenous gadolinium contrast.
(Inclusion Criterion #15 was removed in Amendment 6)
Patients must have a negative COVID-19 test within 72 hours of the first dose of study drug (Cycle 1, Day 1). Patients who had documented COVID-19 infection within 90 days of treatment but more than 20 days from...
(Inclusion Criterion #17 was removed in Amendment 6)

What rules you out

Patients who meet any of the following criteria will be excluded from the study:
(Exclusion Criterion #1 was removed in Amendment 3)
Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC206 (e.g., ONC201) or its excipients.
Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
Patients who are unable or unwilling to abide by the study protocol or cooperate fully with the Investigator.
Patients with a known HIV-positive test on combination anti-retroviral therapy are ineligible for this initial first-in-human trial because of the potential for PK interactions with ONC206.
Patients with active cardiac disease, including any of the following:
Corrected QT interval (QTc) ≥470 msec on screening electrocardiogram (ECG; using the QTc by Fridericia's [QTcF] formula);
Angina pectoris that requires the use of anti-anginal medication;
Ventricular arrhythmias except for benign premature ventricular contractions;
Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication;
Conduction abnormality requiring a pacemaker;
Valvular disease with documented compromise in cardiac function; and/or
Symptomatic pericarditis.
Patients with a history of cardiac dysfunction including any of the following:
Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction function;
History of documented congestive heart failure (New York Heart Association functional classification III-IV); and/or
Documented cardiomyopathy.
Patients who have had an ischemic or hemorrhagic stroke in the last 3 months. If the patient has had a recent tumor resection, cerebral ischemic or hemorrhagic changes that occur peri operatively are not an exclusion.
Patients with refractory epilepsy are excluded. Patients with primarily or secondarily generalized seizures in the 28 days prior to study enrollment will be excluded. Peri-operative seizures, defined as seizures...
Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ONC206 (uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
Patients who have been treated with any hematopoietic colony-stimulating growth factors (CSFs) (e.g., granulocyte-CSF, granulocyte-macrophage-CSF) ≤2 weeks prior to starting study drug. Erythropoietin or darbepoetin...
Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin derivative anticoagulant.
Patients who are taking strong inhibitors or inducers of cytochrome P450 (CYP) 3A4, 2D6, 1A2, 2C9, and 2C19 within at least 14 days prior to the first dose of study drug (Cycle 1, Day 1); these medications are excluded...
Women who are pregnant or breast feeding.
Women of child-bearing potential with a positive serum pregnancy test ≤72 hours prior to the first dose of study drug (Cycle 1, Day 1).
Patients who are receiving concomitant standard and/or investigational anti-cancer therapy.
Patients with alcohol or substance abuse which, in the opinion of the Investigator, would interfere with compliance or safety.
Patients with the presence of any other serious and/or unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with patients' safety, obtaining informed consent or...
Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, or men who do not agree to use highly effective contraception during treatment and for 16 additional weeks after the...
True abstinence: When this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable...
Sterilization: Females must have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In case of oophorectomy alone, only when the reproductive status of the woman...
Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). For female patients on the study, the vasectomized male partner should be the sole partner for...
If patients are not practicing true abstinence and/or if the patient or sexual partner have not had a sterilization procedure as listed above, patients and their sexual partners must follow double barrier contraception...
Females of childbearing potential:
Must use an intrauterine device or intrauterine system, during dosing of any study agent and for 16 weeks after final dose of study drug; or
Must use a double barrier method of contraception: use of an occlusive cap (diaphragm or cervical/vault cap) with spermicide for women combined with use of a condom by their male partners capable of conceiving offspring.
Males capable of conceiving offspring must use condoms during dosing of study agent and for an additional 16 weeks after final dose of study drug. Note: Oral, implantable, or injectable contraceptives may be affected by...
Previous receipt of ONC201, placebo, or blinded study drug from an ONC201 clinical study, or from any other source for H3 K27M-mutant diffuse glioma on or after 01 January 2023.

The study team makes the final eligibility decision.

Where it's taking place

Bethesda, Maryland, United States

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Bethesda, Maryland, United States. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.