PNOC022: A Combination Therapy Trial using an Adaptive Platform Design for Children and Young Adults with Diffuse Midline Gliomas (DMGs) including Diffuse Intrinsic Pontine Gliomas (DIPGs) at Initial Diagnosis, Post-Radiation Therapy and at Time of Progressio
- Conditions
- Diffuse midline glioma'sHigh grade brain tumors10029211
- Registration Number
- NL-OMON53539
- Lead Sponsor
- Prinses Máxima Centrum voor Kinderoncologie
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 30
Cohort 1A and 1B (participants with newly diagnosed DMG prior to radiation
therapy)
-New diagnosis of DMG with imaging and/or pathology consistent with a DMG,
including spinal cord tumors. In cohort 1B, previous tumor tissue confirmation
of DMG is mandatory and pathology must be consistent with a DMG including
diffuse midline glioma H3K27M mutant; WHO Grade 3 and 4 H3 wildtype gliomas.
Cohort 2A and 2B (participants with DMG who have completed radiation therapy)
-Diagnosis of DMG with imaging and/or pathology consistent with a DMG,
including spinal cord tumors, who have completed standard-of-care radiation
therapy. In cohort 2B, previous tumor tissue confirmation of DMG is mandatory
and pathology must be consistent with a DMG including diffuse midline glioma
H3K27M mutant; WHO Grade 3 and 4 H3 wildtype gliomas.
-Participants must be within 4-14 weeks of completion of radiation.
Cohort 3A and 3B (participants with DMG at progression)
-Diagnosis of recurrent DMG with imaging and/or pathology consistent with a
DMG, including spinal cord tumors, who have completed standard-of-care
radiation therapy. In Cohort 3B, previous tumor tissue confirmation of DMG is
mandatory and pathology must be consistent with a DMG including diffuse midline
glioma H3K27M mutant; WHO Grade 3 and 4 H3 wildtype gliomas.
-Participants must have evidence of progression and not have received any
treatment for this progression and have not previously received re-irradiation.
All Cohorts
-Age 2 to 39 years.
-Participants must have recovered from all acute side effects of prior therapy.
-Participant body weight must be above the minimum necessary for the
participant to receive ONC201 (at least 10 kg).
-From the projected start of scheduled study treatment, the following time
periods must have elapsed: At least 7 days after last dose of a biologic agent
or beyond time during which adverse events are known to occur for a biologic
agent, 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 (21 days for bevacizumab when used for tumordirected
therapy, guidance on use for pseudoprogression is below), or 4 weeks (or 5
halflives, whichever is shorter) from other anti-tumor therapies.
o For participants who have received radiotherapy, participants in Cohort 2
must be between 4 and 14 weeks from the completion of local up-front
radiotherapy and not have received additional therapy beyond completion of
radiation therapy.
o The use of bevacizumab to control radiation therapy-induced edema is allowed
(if used for tumor-directed therapy, please see required time period above).
* Dosing limitations are as follows: Bevacizumab (or equivalent) for up to a
maximum of 5 doses, dosing per institutional standard. There is no required
washout period.
* Prior use of temozolomide during radiation at maximum of the standard
pediatric dosing (defined as 90 mg/m2 /dose continuously during radiation
therapy for 42 days) or dexamethasone is allowed. Corticosteroids: Participants
who are receiving dexamethasone must be on a stable or decreasing dose for at
least 3 days prior to baseline MRI scan.
-The participant must have adequate organ function (see protocol for details;
protocol v3.0 dd 26JAN2023
Cohort 1A and 1B (participants with newly diagnosed DMG prior to radiation
therapy)
-Prior exposure to radiation therapy.
-Thalamic H3K27M DMG*
Cohort 2A and 2B
-For tumors that do not have a pontine or spinal cord epicenter the following
specific exclusion criteria apply:
--Thalamic H3K27M DMG that has undergone standard radiation without concurrent
therapy (other than temozolomide)*
Cohort 1A and 2A (participants with newly diagnosed DMG prior to radiation
therapy and who have not previously undergone tumor tissue collection prior to
study entry)
-Deemed not appropriate for tissue resection/biopsy.
Cohort 3A and 3B (participants with DMG at progression)
-Prior exposure to re-irradiation for tumor progression.
-Patients who participated in trials investigating ONC201 in the upfront
setting will not be eligible. Prior ONC201 exposure as part of PNOC022 or
expanded access programs will be allowed.*
All Cohorts
-Diagnosis of a histone H3 wildtype Grade 2 diffuse astrocytoma
-Investigational Drugs
o Participants who are currently receiving another investigational drug.
Investigational imaging agents or agents used to enhance tumor visibility on
imaging or during tumor biopsy/resection should be discussed with the study
chairs.
-Anti-cancer Agents
o Participants who are currently receiving other anti-cancer agents.
-Participants with a known disorder that affects their immune system, such as
HIV or Hepatitis B or C, or an auto-immune disorder requiring systemic
cytotoxic or immunosuppressive therapy. Note: Participants that are currently
using inhaled, intranasal, ocular, topical or other non-oral or non-IV steroids
are not necessarily excluded from the study but need to be discussed with the
study chair.
-Participants with uncontrolled infection or other uncontrolled systemic
illness.
-Female participants of childbearing potential must not be pregnant or
breast-feeding. Female participants of childbearing potential must have a
negative serum or urine pregnancy test prior to the start of therapy (as
clinically indicated).
-Active illicit drug use or diagnosis of alcoholism.
-History of allergic reactions attributed to compounds of similar chemical or
biologic composition as the agents used in study.
-Evidence of disseminated disease, including multi-focal disease, diffuse
leptomeningeal disease or evidence of CSF dissemination.
-Known additional malignancy that is progressing or requires active treatment
within 3 years of start of study drug.
-Concomitant use of potent 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 I), during the treatment phase of the
study and within 2 weeks prior to starting treatment. Concurrent
corticosteroids is allowed.
*Exclusion criteria do not apply to patient of <=18 years old who have thalamic
disease; these patients can still be included in the PNOC022 trial at the
Prinses Máxima Center. Exclusion criteria do apply to patients over the age of
18 years old who have thalamic disease. These patients can be enrolled in the
ACTION trial.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Cohort 1 and 2: progression-free survival at 6 months<br /><br>Cohort 3: overall survival at 7 months</p><br>
- Secondary Outcome Measures
Name Time Method