Study on the Safety and Effectiveness of NEO212 for Patients with Certain Brain Tumors or Brain Metastasis

Inclusion Criteria

• Patient must be ≥ 18yrs of age.

• Patient must have the ability to understand, and the willingness to sign, a written informed consent form.

• Patient has been on a stable or decreasing dose of steroids for at least five days prior to the date of informed consent.

• Any toxicity from prior therapy must be resolved or at maximum Grade 1 prior to initiation of NEO212.

• If progression of disease occurs within 90 days or conformal radiation, the progression/recurrence must be outside of the radiation field or proven by biopsy/resection.

• Patient with Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype must have a Karnofsky Performance Status (KPS) of ≥ 60.

• Patient with select solid tumors (see Appendix 2) must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

• Patient must have an expected survival or at least three months.

• Patient must have a baseline MRI of the brain with gadolinium within 14 days of administration of NEO212.

• Patient with select solid tumors (see Appendix 2) must have a baseline CT scan with IV contrast and oral contrast of neck, chest, abdomen and pelvis within 14 days of administration of NEO212.

• Patients must be able to comply with all study assessments.

• If patient suffers from seizures (s)he must be controlled on a stable dose of anti-epileptics for 14-days prior to the date of informed consent.

• Patient must have adequate organ and marrow function as follows:

  • Absolute neutrophil count ≥ 1,500/microliter
  • Platelets ≥ 100,000/microliter
  • Total bilirubin within normal institutional limits
  • AST (SGOT) / ALT (SPGT) ≤ 2.5 x institutional upper limit of normal
  • Creatinine clearance (CrCl) of >60 mL/min (using the Cockcroft-Gault formula or 24- hour urine collection).

• Female patients of child-bearing potential and male patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for 30 days prior to the first dose of NEO212, for the duration of study participation, and for 90 days following completion of therapy.

A female of child-bearing potential is any women (regardless of sexual orientation, not having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has not had menses at any time in the preceding 12 consecutive months).
• A negative serum pregnancy test will be required of all female patients of child-bearing potential within seven days prior to the receipt of NEO212.
• A serum pregnancy test will be repeated immediately if pregnancy is suspected.

Phase 1: (dose escalation)

• Patient must:

  • have radiographically confirmed Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype following previous radiation therapy or treatment with temozolomide and radiation, or
  • have select solid tumors (see Appendix 2) with uncontrolled metastases to the brain (confirmed by cranial CT or MRI) that is not controlled by surgery or radiation therapy and receiving one of the protocol approved SOC regimens.

• Patients receiving prior systemic therapy must have a minimum wash-out period (defined as the period prior to receipt of the first dose of NEO212) of:

  • 28 days or 5 half-lives (whichever is shorter) elapsed from the administration from any experimental agent;
  • 2 weeks from administration of immunotherapies;
  • 28 days from administration of cytotoxic agents; and
  • 7 days from administration of non-cytotoxic agents (interferon, tamoxifen, thalidomide, cis-retinoic acid, and herbal medicine).

NOTE: No washout is necessary for alternating electrical fields.

Phase 2a: (safety run-in)

• Patient must have select solid tumors (see Appendix 2) with uncontrolled metastases to the brain (confirmed by cranial CT or MRI) that is not controlled by surgery or radiation therapy and receiving one of the protocol approved SOC regimens.
• Patients receiving prior systemic therapy must be receiving one of the protocol approved Standard of Care (SOC) regimens listed on Appendix 1.
• Patient must have measurable/evaluable CNS disease per RANO or RANO-BM criteria.
• Patient must have measurable/evaluable systemic disease per RECIST v1.1 criteria.

Phase 2b: (efficacy)

• Patient must:

  • have radiographically confirmed Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype following previous radiation therapy or treatment with temozolomide and radiation, or
  • have select solid tumors (see Appendix 2) with uncontrolled metastases to the brain (confirmed by cranial CT or MRI) that is not controlled by surgery or radiation therapy and receiving one of the protocol approved SOC regimens.

• Patients receiving prior systemic therapy must be receiving one of the protocol approved Standard of Care (SOC) regimens listed on Appendix 1.

• Patient must have measurable/evaluable CNS disease per RANO or RANO-BM criteria

• Patient with select solid tumors (see Appendix 2) must have measurable/evaluable systemic disease per RECIST v1.1 criteria.

• Creatinine clearance (CrCl) of >60 mL/min (using the Cockcroft-Gault formula or 24-hour urine collection). Female patients of child-bearing potential and male patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for 30 days prior to the first dose of NEO212, for the duration of study participation, and for 90 days following completion of therapy.

9.2

Exclusion Criteria

• Patients in Phase 1 cannot be receiving any other cancer treatments.
• Patients in Phase 2a or 2b cannot be receiving any standard treatments not specified in the study.
• Patients with cancer spread to the spinal cord or the membranes covering the brain and spinal cord are excluded.
• Patients who have had more than one recurrence or progression of their brain tumors are not eligible.
• Patients who have received certain types of brain radiation therapy within two weeks before starting NEO212 are excluded.
• Patients with a history of cancer spread to the brain's protective layers are not eligible.
• Patients with a history of another cancer within the last five years, except for certain skin cancers, are excluded.
• Patients with certain heart conditions or medications affecting heart rhythm are not eligible.
• Patients who had surgery within seven days before starting the study are excluded.
• Patients who have not recovered from side effects of previous cancer treatments are not eligible.
• Patients who have previously been treated with perillyl alcohol or have allergies to it are excluded.
• Patients with autoimmune diseases requiring systemic treatment or conditions needing immunosuppression are not eligible.