GlioblastomaPhase 2NCT04629209
A Phase II, Open Label Study of ONC201 in Adults With EGFR-low Glioblastoma
A Phase 2 study testing ONC201 in people with Glioblastoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
This is an open-label, two arm study. The trial will enroll a total of up to 36 patients. Arm A will enroll up to a total of 6 evaluable patients and Arm B will enroll up to a total of 30 evaluable patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- ONC201
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jun 2024to 30 Jun 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have histologically confirmed World Health Organization Grade IV glioblastoma.
- Patient must have all of the following in their most recently resected archival tumor tissue: (1) absence of EGFR gene amplification by FISH, (2) absence of EGFRvIII expression by RT-PCR, and (3) low EGFR expression by IHC.
- For Arm A: Patients must be eligible for salvage surgical resection as deemed by the site Investigator.
- For Arm B: Unequivocal evidence of recurrence (progressive disease) on contrast-enhanced brain CT or MRI as defined by RANO criteria, or have documented recurrent glioma on diagnostic biopsy.
- Patient must have measurable disease by RANO criteria.
- Patient must have had previous therapy with at least radiotherapy.
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- Patient must have an interval of at least 90 days from the completion of radiotherapy prior to the first dose of ONC201. If patients are within 90 days of radiotherapy, they may still be eligible if they meet one or more of the following criteria.
- Progressive tumor is outside the original high-dose radiotherapy target volume as determined by the treating investigator, or
- Histologic confirmation of tumor through biopsy or resection, or 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.
- From the projected start of ONC201, 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 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.
- Patient must be ≥18 years of age.
- Patient must have a Karnofsky Performance Status (KPS) ≥ 60
- Patient must have 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 ≤ ULN OR creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above normal.
- Patient must have a contrast-enhanced head CT or brain MRI and total spine MRI within 14 days prior to start of study drug.
- Corticosteroid dose must be stable or decreasing for at least 3 days prior to the baseline CT or MRI scan.
- 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.
- WOCBP must have a negative serum or urine pregnancy test within 28 days of initiation of dosing.
- Contraception is not required for men with documented vasectomy.
- Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential.
- Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
- Availability of formalin-fixed paraffin-embedded tumor tissue.
- Patient must have the ability to be able to swallow and retain orally administered medication.
- Patient must have the ability to understand and the willingness to sign a written informed consent document. Only patients who have capacity to consent will be enrolled in the study.
Who cannot join
- Patient has a midline glioma.
- Patient has a known histone H3 K27M mutation.
- Patient has a known IDH1 (isocitrate dehydrogenase 1) or IDH2 mutations or 1p/19q co-deletion.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients (See Section 8).
- Presence of diffuse leptomeningeal disease or evidence of CSF dissemination.
- Current or planned participation in a study of an investigational agent or using an investigational device.
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- 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.
- Pregnant and/or breastfeeding women or unable to maintain use of contraception while on study and for 30 days after the last dose of study drug.
- Known HIV-positive test on combination antiretroviral therapy.
- Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias or bradycardia, unless arrhythmia is controlled and after Cardiology has cleared patient to receive ONC201.
- History of CHF, or MI or stroke in the last 3 months.
- Receiving therapeutic agents known to prolong QT interval.
- Active illicit drug use or diagnosis of alcoholism that would interfere with study compliance or the assessment of outcomes.
- 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, in situ melanoma, 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. An interval of 1 week for stereotactic brain biopsy from the start of ONC201 is acceptable.
- Concomitant use of potent CYP3A4/5 inhibitors during the treatment phase of the study and within 72 hours prior to starting ONC201.
- 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 ONC201. Concurrent dexamethasone is allowed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
This is an open-label, two arm study. The trial will enroll a total of up to 36 patients. Arm A will enroll up to a total of 6 evaluable patients and Arm B will enroll up to a total of 30 evaluable patients. Arm A will explore the intra-tumoral ONC201 concentrations and pharmacodynamic activity in adult EGFR-low glioblastoma patients. Arm B will determine the radiographic efficacy of ONC201 in adult recurrent EGFR-low glioblastoma patients. All patients will be treated with oral ONC201 (625 mg) twice weekly, 2 consecutive days on and 5 days off per week schedule.
- Conditions
- Glioblastoma
- Being tested
- ONC201
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ONC201Drug
ONC201 is a orally active, small molecule DRD2 antagonist that kills cancer cells but not normal cells.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: ONC201 with Surgical Resection in Glioblastoma | Experimental | Patients must be eligible for salvage surgical resection as deemed by the site Investigator. ONC201 will be administered orally, twice a week (2 consecutive days on and 5 days off per week) schedule at a dose of 625mg. Receives: Drug: ONC201 |
| Arm B: ONC201 in Glioblastoma | Experimental | Unequivocal evidence of recurrence (progressive disease) on contrast-enhanced brain CT or MRI as defined by RANO criteria, or have documented recurrent glioma on diagnostic biopsy. ONC201 will be administered orally, twice a week (2 consecutive days on and 5 days off per week) schedule at a dose of 625mg. Receives: Drug: ONC201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intra-tumoral ONC201 concentrations
intra-tumoral ONC201 concentrations in adult EGFR-low glioblastoma patients. The drug concentrations will be measured in micrograms per milliliters.
Measured: 11 Days
Objective Response Rate
Objective Response Rate of ONC201 in adult recurrent EGFR-low glioblastoma patients. Measured using the RANO criteria.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2020
- Study start28 Jun 2024 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion30 Jun 2025 (estimated)
Why it stopped: Change in approach to study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- University of Minnesota
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04629209
- Sponsor's protocol ID
- 2020LS093
- Other IDs
- ONC026
- Status last verified
- Nov 2023
- First submitted
- 10 Nov 2020
- Last updated
- 24 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open Label Study of ONC201 in Adults With EGFR-low Glioblastoma
- ClinicalTrials.gov ID
- NCT04629209
- Acronym / sponsor ID
- 2020LS093
- Conditions
- Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Change in approach to study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Collaborators
- University of Minnesota
- Study start
- 28 Jun 2024 (estimated)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 16 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, two arm study. The trial will enroll a total of up to 36 patients. Arm A will enroll up to a total of 6 evaluable patients and Arm B will enroll up to a total of 30 evaluable patients. Arm A will explore the intra-tumoral ONC201 concentrations and pharmacodynamic activity in adult EGFR-low glioblastoma patients. Arm B will determine the radiographic efficacy of ONC201 in adult recurrent EGFR-low glioblastoma patients. All patients will be treated with oral ONC201 (625 mg) twice weekly, 2 consecutive days on and 5 days off per week schedule.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: ONC201 with Surgical Resection in Glioblastoma | Experimental | Drug: ONC201Patients must be eligible for salvage surgical resection as deemed by the site Investigator. ONC201 will be administered orally, twice a week (2 consecutive days on and 5 days off per week) schedule at a dose of 625mg. |
| Arm B: ONC201 in Glioblastoma | Experimental | Drug: ONC201Unequivocal evidence of recurrence (progressive disease) on contrast-enhanced brain CT or MRI as defined by RANO criteria, or have documented recurrent glioma on diagnostic biopsy. ONC201 will be administered orally, twice a week (2 consecutive days on and 5 days off per week) schedule at a dose of 625mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Patient must have histologically confirmed World Health Organization Grade IV glioblastoma.
- Patient must have all of the following in their most recently resected archival tumor tissue: (1) absence of EGFR gene amplification by FISH, (2) absence of EGFRvIII expression by RT-PCR, and (3) low EGFR expression by IHC.
- For Arm A: Patients must be eligible for salvage surgical resection as deemed by the site Investigator.
- For Arm B: Unequivocal evidence of recurrence (progressive disease) on contrast-enhanced brain CT or MRI as defined by RANO criteria, or have documented recurrent glioma on diagnostic biopsy.
- Patient must have measurable disease by RANO criteria.
Key exclusion criteria (18 listed)
- Patient has a midline glioma.
- Patient has a known histone H3 K27M mutation.
- Patient has a known IDH1 (isocitrate dehydrogenase 1) or IDH2 mutations or 1p/19q co-deletion.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients (See Section 8).
- Presence of diffuse leptomeningeal disease or evidence of CSF dissemination.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ONC201ONC201 is a orally active, small molecule DRD2 antagonist that kills cancer cells but not normal cells. | Drug | Arm A: ONC201 with Surgical Resection in Glioblastoma, Arm B: ONC201 in Glioblastoma |
Primary outcome
Intra-tumoral ONC201 concentrations
Time frame: 11 Days
intra-tumoral ONC201 concentrations in adult EGFR-low glioblastoma patients. The drug concentrations will be measured in micrograms per milliliters.
Objective Response Rate
Time frame: 6 months
Objective Response Rate of ONC201 in adult recurrent EGFR-low glioblastoma patients. Measured using the RANO criteria.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ONC201 in people with Glioblastoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intra-tumoral ONC201 concentrations (time frame: 11 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2023.