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First-in-Human Trial for People with Recurrent Rare CNS Tumors

, by Alyssa Harrell, NCI Communications Fellow

Older woman holding and reading pill bottle with a glass of water and younger woman looking at her phone.
Credit: iStock

NCI-CONNECT launched a first-in-human phase 1 clinical trial for people with recurrent rare brain and spine tumors. Clinical trials are done to find out if a new treatment is safe and effective in humans. Clinical trials are important for rare central nervous system (CNS) cancers because treatment options are limited, especially when the cancer comes back.  

Brett Theeler, M.D., neurologist and neuro-oncologist in the United States Army Medical Corps and clinical collaborator at the NCI Center for Cancer Research's Neuro-Oncology Branch, is taking a hopeful step forward to treat recurrent CNS cancers in a new first-in-human trial with ONC206, an oral, targeted cancer therapy. The trial tests the dosing and safety of ONC206 in adult patients.

“It is rare in neuro-oncology to get an opportunity to perform a first-in-human phase 1 clinical trial, because most drugs go through testing in people with non-CNS tumor types before we can test them in people with CNS tumors,” says Dr. Theeler.

This trial is a first step in the development of a novel drug for primary brain tumor patients.

Brett Theeler, M.D.

The trial aims to find the maximum safely tolerated dose of ONC206 in people with recurrent primary CNS tumors. The dose and schedule determined in this phase 1 trial can be used for next phase ONC206 studies to see if it is an effective treatment that can improve outcomes for patients. 

Understanding the Trial Design

The rationale for studying ONC206 is based on ONC201, a previously studied drug that similarly blocks dopamine receptors, which are prominent proteins in the CNS. The ONC201 drug has shown benefit in some patients with diffuse midline gliomas with histone mutations, an incurable and aggressive type of brain cancer.

Other CNS tumors that have dopamine receptors include glioblastoma, lower grade gliomas, and medulloblastoma. Because ONC206 has the same mechanism of action as ONC201 but is a more potent blocker of dopamine receptors, the new trial will include all of the NCI-CONNECT rare CNS tumor types.

The ONC206 study is a basket trial, which means it is studying patients who have different types of cancer. “Basket trials for rare cancers are optimal, because even a small number of treatment responses could serve as motivation for a larger clinical trial,” says Dr. Theeler. “And this trial is unique because it includes rare primary CNS tumors, which are often not included in early phase clinical trials. Most phase 1 trials in neuro-oncology are for recurrent glioblastomas.”

Knowing the Criteria

The clinical trial is for adults (age 18 or older) with recurrent primary brain or spine tumors. Participants must be able to take oral capsules, have had no major surgeries four weeks prior to beginning the trial, and meet the additional entrance criteria.

Trial participants are given the drug ONC206 to take orally once per week. The dose can be taken at home or during hospital visits. As the trial continues, patients may be enrolled in a trial arm where they receive the drug two or more days per week. This trial requires multiple visits to NIH in Bethesda, Maryland for lab tests, safety evaluations, and other follow-up appointments each month.

“We ensure that participants feel appreciated, supported, and cared for while on the trial,” says Kelly Mentges, the Neuro-Oncology Branch research nurse for the trial. “Treatment options for these cancer types are definitely an unmet need, and hopefully this study will be one of the first to introduce another viable treatment option for people with brain and spine tumors.”

For questions or to enroll in this study, the patient's treating physician can contact the Neuro-Oncology Branch.

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