Assessment of the safety and efficacy of ONC206 in children with malignant brain tumors

Switzerland, United States (ICTRP)

ID di studio ICTRP
NCT04732065 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
Open label Phase 1 and Target Validation study of ONC206 in Children and Young Adults with Newly Diagnosed or Recurrent Diffuse Midline Glioma (DMG), and Other Recurrent Primary Malignant Central Nervous System (CNS) Tumors (BASEC)

Titolo accademico
PNOC023: Open Label Phase 1 and Target Validation Study of ONC206 in Children and Young Adults With Newly Diagnosed or Recurrent Diffuse Midline Glioma (DMG), and Other Recurrent Primary Malignant Central Nervous System (CNS) Tumors (ICTRP)

Titolo pubblico
ONC206 for Treatment of Newly Diagnosed, Recurrent Diffuse Midline Gliomas, and Other Recurrent Malignant CNS Tumors (ICTRP)

Malattie studiate
Diffuse Midline Glioma (DMG);Glioblastoma;Recurrent Ependymoma;Recurrent Malignant Central Nervous System Neoplasm;Spinal Cord Glioma;World Health Organization (WHO) Grade III Glioma;CNS Tumor;Central Nervous System Tumor (ICTRP)

Intervento studiato
Drug: ONC206;Radiation: Standard of Care Radiation Therapy;Procedure: Optional Proton (1H) MR spectroscopy (MRS) (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
Gender: All
Maximum age: 21 Years
Minimum age: 2 Years
Inclusion Criteria:

- ARM A: Children and young adults with DMG, H3K27 altered (Dose escalation: 2-21
years of age; Dose expansion: 2 years of age and above) who completed at least one
line of prior therapy. Prior treatment must have included focal radiation therapy
and patients must be within 4-14 weeks from completion of radiation therapy to
registration (patients must start treatment within 1 week from registration), have
not started any other therapies post-radiation, and have no evidence of disease
progression.

- ARM A: Tumor tissue confirmation of DMG, H3K27 altered is mandatory and pathology
must be consistent with a DMG, H3K27 altered.

- ARM A: Participants must have recovered from all acute side effects of prior
therapy.

- ARM A: From the projected start of scheduled study treatment, 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), 4
weeks from antibodies and must be at least 7 days since the completion of therapy
with a biologic or small molecule agent. For any biologic or small molecule agent
with known adverse events that can occur beyond 7 days after administration, the
period prior to enrollment must be beyond the time during which adverse events are
known to occur (these should be discussed with the study team)

- ARM B: Newly diagnosed children and young adults (Dose escalation: 2-21 years of
age; Dose expansion: 2 years of age and above) with a diagnosis of DMG, H3K27
altered are eligible, including spinal cord DMGs.

- ARM B: Tumor tissue confirmation of DMG is mandatory and pathology must be
consistent with a DMG, H3K27 altered.

- ARM C: Children and young adults with DMGs (Dose escalation: 2-21 years of age; Dose
expansion: 2 years of age and above) who have evidence of progression but have not
been treated for this progression and are recommended to get re-irradiation.

- ARM C: Patients must have undergone prior focal radiation therapy as part of their
initial therapy and should be at least 6 months from prior radiation therapy. If
timing is less than 6 months from prior focal radiation, these patients need to be
discussed with the study chair(s).

- ARM C: Tumor tissue confirmation is mandatory and pathology must be consistent with
a DMG, H3K27 altered.

- ARM C: Participants must have recovered from all acute side effects of prior therapy

- ARM C: From the projected start of scheduled study treatment, 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), 4
weeks from antibodies and must be at least 7 days since the completion of therapy
with a biologic or small molecule agent. For any biologic or small molecule agent
with known adverse events that can occur beyond 7 days after administration, the
period prior to enrollment must be beyond the time during which adverse events are
known to occur (these should be discussed with the study team)

- ARM D: Children and young adults with recurrent primary malignant CNS tumors (Dose
escalation: 2-21 years of age; Dose expansion: 2 years of age and above ) who have
evidence of progression but have not been treated for this progression .
Participants who received a surgical resection for that progression are eligible if
surgery has no curative intent. These patients need to be discussed with the study
team.

- ARM D: Prior tumor tissue confirmation is mandatory and pathology from the primary
tumor must be consistent with malignant CNS tumor (diagnosis of ependymoma is
allowed).Tissue at the time of progression is not required.

- ARM D: Participants must have recovered from all acute side effects of prior therapy

- ARM D: From the projected start of scheduled study treatment, 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), 4
weeks from antibodies and must be at least 7 days since the completion of therapy
with a biologic or small molecule agent. For any biologic or small molecule agent
with known adverse events that can occur beyond 7 days after administration, the
period prior to enrollment must be beyond the time during which adverse events are
known to occur (these should be discussed with the study team). Bevacizumab used for
pseudoprogression does not require a wash out period.

- TARGET VALIDATION: Newly diagnosed children and adults (2 years of age and above)
with imaging consistent with a DMG, H3K27 altered are eligible.

- TARGET VALIDATION: Children and young adults with recurrent primary malignant CNS
tumors, including recurrent DMG, (2 years of age and above) who have evidence of
progression but have not been treated for this progression.

- TARGET VALIDATION: Participants must undergo tumor tissue collection as part of
their standard of care

- Participants who are receiving steroids must be on a stable or decreasing dose for
at least 3 days prior to baseline MRI scan.

- Peripheral absolute neutrophil count (ANC) >= neutrophil 1.0 g/l.

- Platelet count >= 100 x 10^9/L (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment).

- Serum creatinine < 1.5 Upper Limit normal (ULN) based on age and gender.

- Total bilirubin <= 1.5 x upper limit of normal (ULN) for age; in presence of
Gilbert's syndrome, total bilirubin < 3 x ULN or direct bilirubin < 1.5 x ULN.

- Alanine aminotransferase (ALT) <= 3 x ULN.

- Aspartate aminotransferase (AST) <= 3 x ULN.

- Patients with seizure disorder may be enrolled if seizure disorder is well
controlled

- The effects of ONC206 on the developing human fetus is unknown. For this reason,
females of child-bearing potential and males must agree to use adequate
contraception. Adequate methods include: hormonal or barrier method of birth
control; or abstinence prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while she
or her partner is participating in this study, she should inform her treating
physician immediately. Males treated or enrolled on this protocol must also agree to
use adequate contraception prior to the study and for the duration of study
participation

- Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants
=< 16 years of age. Participants who are unable to walk because of paralysis, but
who are up in a wheelchair, will be considered ambulatory for the purpose of
assessing the performance score

- Participants must be willing to provide adequate tissue. A minimum of 10-20 paraffin
embedded unstained slides OR 1 block with tumor content of 40% or greater is
required. Fronzen tissue is also acceptable. Participants who previously enrolled on
PNOC022 and provided adequate tissue, may not need to submit additional tissue -
confirm with Study Ch (ICTRP)

non disponibile

Endpoint primari e secondari
Proportion of participants with dose-limiting toxicities (DLT);Maximum tolerated dose (MTD) of ONC206 (ICTRP)

Mean maximum concentration (Cmax) of ONC206;Mean corresponding time (Tmax) of ONC206;Area under the curve (AUC) of ONC206;Elimination half-life (t1/2) of ONC206;Mean Total body clearance (CL) for ONC206;Mean Volume of Distribution (Vd) for ONC206 (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
Chimerix;Mithil Prasad Foundation;Storm the Heavens Fund;The ChadTough Defeat DIPG Foundation;National Cancer Institute (NCI);Dana-Farber Cancer Institute (ICTRP)

Contatti aggiuntivi
Sabine Mueller, MD, PhD;PNOC Operations, PNOC023@ucsf.edu, (415) 502-1600, University of California, San Francisco, (ICTRP)

ID secondari
NCI-2021-00046, R01CA266596, 200814 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT04732065 (ICTRP)