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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05580562




Registration number
NCT05580562
Ethics application status
Date submitted
27/09/2022
Date registered
14/10/2022
Date last updated
29/05/2024

Titles & IDs
Public title
ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study)
Scientific title
ONC201 for the Treatment of Newly Diagnosed H3 K27M-mutant Diffuse Glioma Following Completion of Radiotherapy: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study
Secondary ID [1] 0 0
ONC201-108
Universal Trial Number (UTN)
Trial acronym
ACTION
Linked study record

Health condition
Health condition(s) or problem(s) studied:
H3 K27M 0 0
Glioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - ONC201
Treatment: Drugs - ONC201 + Placebo
Other interventions - Placebo

Experimental: ONC201 Twice Weekly Group -

Experimental: ONC201 Once Weekly Group -

Placebo Comparator: Placebo Group -


Treatment: Drugs: ONC201
Participants = 52.5 kg will receive 625 mg of ONC201 (5 × 125-mg capsules) dosing days; participants < 52.5 kg will receive a dose (and corresponding number of capsules) scaled by body weight and rounded to 125-mg increments.

Treatment: Drugs: ONC201 + Placebo
Participants = 52.5 kg will receive 625 mg of ONC201 (5 × 125-mg capsules) or matching placebo on dosing days; participants < 52.5 kg will receive a dose (and corresponding number of capsules) scaled by body weight and rounded to 125-mg increments

Other interventions: Placebo
Participants will receive placebo (same number of capsules as the ONC201 dose) on dosing days
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival (OS)
Timepoint [1] 0 0
From date of randomization until date of death from any cause, assessed up to approximately 44 months
Primary outcome [2] 0 0
Progression free survival (PFS) as assessed by using RANO-HGG criteria
Timepoint [2] 0 0
From date of randomization until the date of first documented progression assessed up to approximately 44 months
Secondary outcome [1] 0 0
Incidence of adverse events
Timepoint [1] 0 0
From date of randomization up to 44 months
Secondary outcome [2] 0 0
Change from baseline in clinical laboratory parameters
Timepoint [2] 0 0
From date of randomization up to 44 months
Secondary outcome [3] 0 0
PFS using RANO-HGG criteria
Timepoint [3] 0 0
From date of randomization up to 44 months
Secondary outcome [4] 0 0
Corticosteroid response
Timepoint [4] 0 0
From date of randomization up to 44 months
Secondary outcome [5] 0 0
Performance status response
Timepoint [5] 0 0
From date of randomization up to 44 months

Eligibility
Key inclusion criteria
1. Able to understand the study procedures and agree to participate in the study by
providing written informed consent (by participant or legally authorized
representative), and assent when applicable.

2. Body weight = 10 kg at time of randomization.

3. Histologically diagnosed H3 K27M-mutant diffuse glioma (new diagnosis). Detection of a
missense K27M mutation in any histone H3-encoding gene detected by testing of tumor
tissue (immunohistochemistry [IHC] or next-generation sequencing [NGS] in a Clinical
Laboratory Improvement Amendments [CLIA]-certified or equivalent laboratory). [Site to
provide (as available): = 10 unstained formalin-fixed paraffin-embedded (FFPE) slides
from tumor tissue.]

4. At least one, high-quality, contrast-enhanced MRI of the brain obtained prior to
starting radiotherapy for submission to sponsor's imaging vendor for central read. For
participants who had a surgical resection, this scan must be post-resection; for
participants who did not have a resection, this scan may be pre- or post-biopsy.

5. At least one, high-quality, contrast-enhanced MRI of the brain obtained 2 to 6 weeks
after completion of frontline radiotherapy. If unable to obtain contrast-enhanced
imaging due to lack of venous access after multiple attempts, a patient may still be
eligible after collection of a nonenhanced MRI of the brain. [Site to also provide all
available MRIs completed prior to initiating treatment with study intervention.]

6. Received frontline radiotherapy

1. Initiated radiotherapy within 12 weeks from the initial diagnosis of H3
K27M-mutant diffuse glioma.

2. Completed radiotherapy within 2 to 6 weeks prior to randomization

3. Completed standard fractionated radiotherapy (eg. 54 to 60 Gy in 28 to 33
fractions given over approximately 6 weeks or hypofractionated radiotherapy (eg.
40 Gy in 15 fractions given over approximately 3 weeks).

7. Karnofsky Performance Status or Lansky Performance Status = 70 at time of
randomization.

8. Stable or decreasing dose of corticosteroids and anti-seizure medications for 7 days
prior to randomization, if applicable. Stable steroid dose is defined as = 2 mg/day
increase (based on dexamethasone dose or equivalent dose of an alternative steroid).
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Primary spinal tumor.

2. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter
and diffuse involvement of the pons.

3. Evidence of leptomeningeal spread of disease or cerebrospinal fluid dissemination.

4. Any known concurrent malignancy.

5. New lesion(s) outside of the radiation field.

6. Received whole-brain radiotherapy.

7. Received proton therapy for glioma.

8. Use of any of the following treatments within the specified time periods prior to
randomization:

1. ONC201 or ONC206 at any time.

2. Systemic bevacizumab (includes biosimilars) at any time since the initial
diagnosis of H3 K27M-mutant diffuse glioma.

3. Temozolomide within past 3 weeks.

4. Tumor treating fields at any time.

5. DRD2 antagonist within past 2 weeks.

6. Any investigational therapy within past 4 weeks.

7. Strong CYP3A4 inhibitors within 3 days.

8. Strong CYP3A4 inducers (includes enzyme-inducing antiepileptic drugs) within 2
weeks.

9. Laboratory test results meeting any of the following parameters within 2 weeks prior
to randomization:

1. Absolute neutrophil count < 1.0 × 109/L or platelets < 75 × 109/L.

2. Total bilirubin > 1.5 × upper limit of normal (ULN) (participants with Gilbert's
syndrome may be included with total bilirubin > 1.5 × ULN if direct bilirubin is
= 1.5 × ULN).

3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN.

4. Creatinine clearance = 60 mL/min as calculated by the Cockcroft Gault equation
(or estimated glomerular filtration rate < 60 mL/min/1.73 m2).

10. QTc > 480 msec (based on mean from triplicate electrocardiograms) during screening.

11. Known hypersensitivity to any excipients used in the study intervention formulation.

12. Pregnant, breastfeeding, or planning to become pregnant while receiving study
intervention or within 3 months after the last dose. Participants of childbearing
potential must have a negative serum pregnancy test within 72 hours prior to receiving
the first dose of study intervention.

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

14. Any other condition (eg, medical, psychiatric, or social) that, in the opinion of the
investigator, may interfere with participant safety or the ability to complete the
study according to the protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/01/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2026
Actual
Sample size
Target
450
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
Royal North Shore Hospital - Sydney
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [4] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [5] 0 0
Olivia Newton-John Cancer Research Institute (ONJCRI) - Heidelberg
Recruitment hospital [6] 0 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2065 - Sydney
Recruitment postcode(s) [3] 0 0
- Herston
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
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United States of America
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Arizona
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California
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Connecticut
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District of Columbia
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Florida
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Georgia
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Indiana
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Wien
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London
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Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Chimerix
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, double-blind, placebo-controlled, parallel-group, international, Phase
3 study in patients with newly diagnosed H3 K27M-mutant diffuse glioma to assess whether
treatment with ONC201 following frontline radiotherapy will extend overall survival and
progression-free survival in this population. Eligible participants will have histologically
diagnosed H3 K27M-mutant diffuse glioma and have completed standard frontline radiotherapy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05580562
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Tarapore, PhD
Address 0 0
Country 0 0
Phone 0 0
1-919-806-1074
Fax 0 0
Email 0 0
clinicaltrials@chimerix.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05580562