Testing NEO212 for treating certain brain tumors and metastases

An Open-label Phase 1/2 Dose Finding, Safety and Efficacy Study of Oral NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Uncontrolled Brain Metastasis in Patients With Select Solid Tumors.

This study is testing a new treatment called NEO212 for people with certain types of brain tumors to see if it is safe and effective when combined with standard treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 134 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Neonc Technologies, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 6 sites (Beverly Hills, California and 5 other locations)
• Trial ID: NCT06047379 on ClinicalTrials.gov

What this trial studies

This multi-site, Phase 1/2 clinical trial evaluates the safety, pharmacokinetics, and efficacy of NEO212 in patients with radiographically-confirmed progression of Astrocytoma IDH-mutant and Glioblastoma IDH-wildtype, as well as those with uncontrolled brain metastases. The trial consists of a dose escalation Phase 1 to determine the maximum tolerated dose (MTD) of NEO212, followed by a safety run-in Phase 2a to confirm the MTD when combined with standard of care treatments. Up to 54 patients will be enrolled across the phases to assess the treatment's effectiveness and safety profile.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with specific types of brain tumors or solid tumors that have metastasized to the brain.

Not a fit: Patients with stable disease not requiring treatment or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with aggressive brain tumors and metastases.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination and regimen is novel.

Eligibility criteria

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 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 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 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 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.
* 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 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.
* Patient must have measurable/evaluable CNS disease per RANO or RANO-BM criteria
* Patient with select solid tumors 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.

Exclusion Criteria: (all Phases)

* Patient in Phase 1 concurrently receiving any other antitumor therapy.
* Patient in Phase 2a or 2b who is concurrently receiving any SOC therapy not listed in Appendix 1.
* Patients with metastases to the spinal cord parenchyma.
* Patients with metastases to the meninges.
* Patient has received stereotactic or highly conformal radiotherapy to CNS lesions within 2 weeks before receipt of NEO212.
* Patient with history of known leptomeningeal involvement.
* Patient has prior history or new diagnosis of secondary cancer within five years prior to the date of informed consent, except for basal cell carcinoma or squamous cell carcinoma of the skin.
* Patient has a corrected QT interval (using Fridericia's correction formula) (QTcF) of \>470 msec, a history of additional risk factors for TdP (e.g. heart failure, hypokalemia), and/or the use of concomitant medications that prolong QT/QTc interval.
* Patient had surgery within 7 days prior to the date of informed consent.
* Patient has not recovered to Grade 1 from treatment related adverse events due to chemotherapy, immunotherapy, or radiation therapy.
* Patient had prior treatment with perillyl alcohol.
* Patient has a history of allergic reactions attributed to perillyl alcohol.
* Patients in Phase 2b with Astrocytoma IDH-mutant, or Glioblastoma IDH-wildtype who have had more than one recurrence or progression of his/her primary CNS tumor(s).

Where this trial is running

Beverly Hills, California and 5 other locations

• Precision NextGen Oncology — Beverly Hills, California, United States (Recruiting)
• OPN Healthcare, Inc — Glendale, California, United States (Recruiting)
• University of Southern California — Los Angeles, California, United States (Recruiting)
• Vanderbilt University Medical Center — Nashville, Tennessee, United States (Recruiting)
• Baylor, Scott and White Research Institute — Dallas, Texas, United States (Recruiting)
• Northwest Medical Specialties — Tacoma, Washington, United States (Recruiting)

Study contacts

• Study coordinator: Christopher Beardmore

Conditions Diffuse Astrocytoma, IDH-Mutant; Glioblastoma, IDH-wildtype; Brain Metastases, Adult; Cervical Cancer; Colorectal Cancer; Esophageal Cancer; Esophageal Squamous Cell Carcinoma; Gastric Cancer