Glasdegib (PF-04449913) With Temozolomide Newly Diagnosed Glioblastoma

Inclusion Criteria

• •Ability to understand and the willingness to sign a written informed consent document.
• •Male or Female ≥18 years old.
• •Newly diagnosed GBM confirmed by biopsy or resection no more than 4 to 6 weeks before registration.
• •Patients candidates for Stupp treatment
• •Patients must have at least 15 unstained slides or 1 tissue block (frozen or paraffin embedded) available from a prior biopsy or surgery (archival tumor material).
• •Patients must have sufficient time for recovery from prior surgery (at least 4 weeks).
• •ECOG ≤ 1.
• •Adequate hematologic function: Hematocrit ≥ 29%, Leukocytes \> 3,000/mcL, ANC ≥ 1,500 cells/ul, platelets ≥ 100,000 cells/ul.
• •Adequate liver function: Bilirubin ≤ 2 x ULN; AST (SGOT) ≤ 2.5 X ULN
• •Creatinine within normal institutional limits or creatinine clearance \> 60 mL/min for subjects with creatinine levels above institutional normal.
• •The effects of SHH pathway inhibitors on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence; surgical sterilization) prior to study entry and for the duration of study participation and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
• •Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 2 weeks prior to starting treatment.
• •Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
• •Patients who have had prior stereotactic radiotherapy, convection enhanced delivery or brachytherapy (as gliosis/scarring from these modalities may limit delivery).
• •Pregnant women are excluded from this study because the potential for teratogenic or abortifacient effects is unknown (glasdegib has been shown to be teratogenic in nonclinical embryo-fetal development studies in rats and mice at subtherapeutic exposures). Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated.
• •HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to glasdegib.
• •Other severe acute or chronic medical condition, uncontrolled intercurrent illness or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.
• •Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 180 days after the last dose of the study treatment.