HIF-2 Alpha Inhibitor PT2385 in Treating Patients With Recurrent Glioblastoma
Condition: Recurrent Glioblastoma
MeSH terms: Glioblastoma; Recurrence
Intervention: HIF-2alpha Inhibitor PT2385; Pharmacological Study; Laboratory Biomarker Analysis; Pharmacogenomic Study
Intervention description: Given PO; Correlative studies; Correlative studies; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well HIF-2 alpha inhibitor PT2385 works in treating patients
      with recurrent glioblastoma. HIF-2 alpha inhibitor PT2385 may stop the growth of tumor cells
      by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  • Patients must have histologically confirmed glioblastoma that is progressive or
             recurrent following radiation therapy and temozolomide according to the Response
             Assessment in Neuro-Oncology (RANO) criteria with:

               -  New contrast-enhancing lesion outside of radiation field on decreasing, stable,
                  or increasing doses of corticosteroids

               -  Increase by >= 25% in the sum of the products of perpendicular diameters between
                  the postradiotherapy scan with the smallest tumor measurement and a scan at least
                  12 weeks from completion of radiation therapy (RT) + temozolomide (TMZ), on
                  stable or increasing doses of corticosteroids

                  ** Note: clinical deterioration not attributable to concurrent medication or
                  comorbid conditions is sufficient to declare progression on current treatment but
                  not for entry onto a clinical trial for recurrence

                    -  Tumor O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation status
                       must be available; results of routinely used methods for MGMT methylation
                       testing (e.g. mutagenically separated polymerase chain reaction, (MSPCR), or
                       quantitative polymerase chain reaction (PCR)) are acceptable

                    -  Patients must have a tumor tissue form indicating availability of archived
                       tissue from a previous surgery for glioblastoma, completed and signed by a
                       pathologist

                    -  Patients must have measurable (defined by at least 1 cm x 1 cm)
                       contrast-enhancing disease by magnetic resonance imaging (MRI) imaging
                       within 21 days of starting treatment

                    -  Patients must be able to undergo MRI of the brain with gadolinium; patients
                       must be maintained on a stable or decreasing dose of corticosteroid regimen
                       (no increase for 5 days) prior to this baseline MRI

                    -  Patients must be in first recurrence of glioblastoma following radiation
                       therapy and temozolomide

                    -  Patients must have recovered from severe toxicity of prior therapy; the
                       following intervals from previous treatments are required to be eligible:

               -  12 weeks from the completion of radiation

               -  6 weeks from a nitrosourea chemotherapy

               -  3 weeks from a non-nitrosourea chemotherapy

               -  4 weeks from any investigational (not Food and Drug Administration
                  (FDA)-approved) agents

               -  2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g.,
                  erlotinib, hydroxychloroquine, etc.)

                    -  Patients must have a Karnofsky performance status >= 60% (i.e. the patient
                       must be able to care for himself/herself with occasional help from others)

                    -  Absolute neutrophil count >= 1,500/microliter (mcL)

                    -  Platelets >= 100,000/mcL

                    -  Hemoglobin >= 9 g/dL

                    -  Total bilirubin =< institutional upper limit of normal

                    -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
                       (SGOT))/ alanine aminotransferase (ALT) (serum glutamate pyruvate
                       transaminase (SGPT)) =< 4 x institutional upper limit of normal

                    -  Creatinine =< institutional upper limit of normal OR creatinine clearance >=
                       60 ml/min/1.73m^2 for patients with creatinine levels above institutional
                       normal

                    -  Activated partial thromboplastin time (APTT) or partial thromboplastin time
                       (PTT) =< 1.5 x institutional upper limit of normal

                    -  Patients must be able to provide written informed consent

                    -  Women of childbearing potential must have a negative serum pregnancy test
                       prior to study start; women of childbearing potential and men must agree to
                       use adequate contraception (hormonal or barrier method of birth control;
                       abstinence) prior to study entry, for the duration of study participation,
                       and through 30 days after the last dose of study drug; should a woman become
                       pregnant or suspect she is pregnant while participating in this study, she
                       should inform her treating physician immediately; men treated or enrolled on
                       this protocol must also agree to use adequate contraception prior to the
                       study, for the duration of study participation, and through 30 days after
                       the last dose of study drug

                    -  Patients must have no concurrent malignancy except curatively treated basal
                       or squamous cell carcinoma of the skin or carcinoma in situ of the cervix,
                       breast, or bladder; patients with prior malignancies must be disease-free
                       for >= five years

                    -  Patients must be able to swallow tablets

        Exclusion Criteria:

          -  • Patients receiving any other investigational agents are ineligible

               -  Patients must not have received prior anti- Vascular endothelial growth factor
                  (VEGF) therapy including bevacizumab (i.e. patients must be bevacizumab naive)

               -  Patients with a history of allergic reactions attributed to compounds of similar
                  chemical or biologic composition to PT2385 are ineligible

               -  Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for
                  treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic
                  drugs or not be taking any anti-epileptic drugs; patients previously treated with
                  EIAED may be enrolled if they have been off the EIAED for 10 days or more prior
                  to the first dose of PT2385

               -  Patients with a history of bleeding diathesis are ineligible

               -  Patients who have not recovered to < Common Terminology Criteria for Adverse
                  Events (CTCAE) grade 2 toxicities related to prior therapy are ineligible

               -  Patients with uncontrolled intercurrent illness including, but not limited to,
                  ongoing or active infection, symptomatic congestive heart failure, clinically
                  significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, or
                  psychiatric illness/social situations that would limit compliance with study
                  requirements, are ineligible

               -  Pregnant women are excluded from this study; breastfeeding should be discontinued
                  if the mother is treated with PT2385

               -  Human immunodeficiency virus (HIV)-positive patients on combination
                  antiretroviral therapy are ineligible due to potential drug-drug interactions
                  with PT2385