PNOC029: Evaluating how tolerable and effective targeted treatment with Tovorafenib is in children and young adults with craniopharyngiomaTovorafenib for the Treatment of Newly Diagnosed or Recurrent Craniopharyngioma in Children and Young Adults

Inclusion

Inclusion Criteria:

Newly Diagnosed Participants:

• Newly diagnosed craniopharyngioma, as based on imaging characteristics and central radiology review. Participants will initially be screened within confines of a screening consent and only those participants with findings consistent with craniopharyngioma and without findings suggesting an indeterminate lesion or lesion of an alternative diagnosis (including abnormal tumor markers found in blood or cerebral spinal fluid (CSF), if completed as part of standard of care (SOC) work-up or if lesion concerning for alternate diagnosis) will move ahead with enrollment on the treatment protocol. Additionally, for participants that have undergone initial biopsy to confirm diagnosis, are within 6 weeks of radiographic diagnosis, and are planned to undergo follow up second surgery for additional tumor resection as per standard of care recommendations, these participants will also be considered eligible.
• Participants must be surgical candidates for biopsy or resection and planned for standard of care biopsy or resection.

Recurrent Participants:

• Recurrent craniopharyngioma, as based on histologic confirmation at time of initial diagnosis (participants with Adamantinomatous craniopharyngioma (ACP) will only be eligible for the recurrent arm).
• Recurrent craniopharyngioma without prior histologic confirmation will initially be screened within confines of a screening consent and only those participants with findings consistent with craniopharyngioma and without findings suggesting an indeterminate lesion or lesion of an alternative diagnosis (including abnormal tumor markers found in blood or CSF, if completed as part of SOC work-up or if lesion concerning for alternate diagnosis) will move ahead with enrollment on the treatment protocol.
• Participants should be surgical candidates for biopsy or resection. If participants are not surgical candidates, but have available archival tumor tissue, they will be enrolled into the exploratory cohort.
• Participants must be willing to provide archival tissue, a minimum of 10-20 paraffin embedded unstained slides OR 1 block with tumor content of 40% or greater is required. Participants who do not meet this criteria may be discussed on a case-by-case basis with the Study Chair(s).
• Participants can have been previously treated with surgical resection alone, cyst drainage and biopsy alone, radiation therapy, other systemic therapies, or any combination thereof.

• Prior Therapy:

  • Had their last dose of myelosuppressive chemotherapy >= 21 days prior to study registration (>=42 days if nitrosourea therapy).
  • Had their last dose of hematopoietic growth factor >=14 days (long-acting growth factor) or >=7 days (short-acting growth factor) prior to study registration, or beyond the time during which adverse events (AEs) are known to occur.
  • Had their last dose of biologic (anti-neoplastic agent) >=7 days prior to study registration, or beyond the time during which AEs are known to occur.
  • Had their last dose of monoclonal antibodies >=21 days prior to study registration.

Radiation:

• Had their last fraction of local irradiation to primary tumor >=12 weeks prior to registration; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression.
• At least 14 days after local palliative radiation (small-port).

All Participants:

• Age 1 to 39 years.
• Participants continuing on maintenance therapy after standard of care biopsy/resection must have measurable disease, as defined as lesions that can be accurately measured in two dimensions (longest diameter to be recorded) with a minimum size of no less than double the slice thickness. Previously irradiated lesions are considered non-measurable except in cases of documented progression of the lesion since the completion of radiation therapy. Participants without measurable disease may continue on study and will be followed for study endpoints, but will not be included as part of target accrual.
• Performance Score: 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.
• Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration. The participant steroid dose should be no more than a steroid-equivalent of dexamethasone 0.1 mg/kg/day (or maximum 4mg/day; whichever is the lower dose) at time of enrollment. Participants that have been stable on physiologic hormone replacement for hypopituitarism are allowed.

• Organ Function Requirements:

  • Adequate Bone Marrow Function defined as:

    • Peripheral absolute neutrophil count (ANC) >=1000/mm3.
    • Platelet count >= 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).

  • Adequate Renal Function defined as-

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

  • Adequate Liver Function defined as-

    • Bilirubin (sum of conjugated + unconjugated) <= 1.5 x upper limit of normal (ULN) for age (except in participants with documented Gilbert syndrome).
    • Serum glutamic-pyruvic transaminase (SGPT)((alanine aminotransferase (ALT)) <= 3 x ULN.
    • Serum albumin >=2 g/dL (20g/L).
  • Adequate Neurologic Function defined as participants with seizure disorder may be enrolled if well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.
  • Adequate Pulmonary Function defined as no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry of > 92% while breathing room air.
  • prothrombin time (PT) /partial thromboplastin time (PTT)/International Normalized Ratio (INR) within institutional normal limits or deemed appropriate for surgical intervention by the treating team for patients undergoing surgery biopsy/resection
• The effects of Tovorafenib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (non-hormonal contraception; barrier method of birth control; abstinence - note, tovorafenib can make hormonal contraceptives ineffective) prior to study entry, for the duration of study participation and 28 days after completion of Tovorafenib administration, whichever is later. 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.
• A legal parent/guardian or participants must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.
• Ability to complete the PedsQL Core Module. Patients must enroll on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution.