Clinical Study

Phase II Trial Of Smo/ Akt/ Nf2/Cdk Inhibitors In Progressive Meningiomas With Smo/ Akt/ Nf2/Cdk Pathway Mutations

Posted Date: May 15, 2019

  • Investigator: Rekha Chaudhary
  • Specialties: Cancer, Oncology
  • Type of Study: Drug

This phase II trial will study how well vismodegib, focal adhesion kinase (FAK) inhibitor GSK2256098, and capivasertib work in treating patients with meningioma that is growing, spreading, or getting worse (progressive). Vismodegib, FAK inhibitor GSK2256098, capivasertib, and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Efficacy will be determined by progression free survival and response rate defined as a confirmed complete response or partial response. There will be 4 arms in this study. In arm A, patients will receive vismodegib PO QD. In arm B, Patients will receive FAK inhibitor GSK2256098 PO BID. In arm 3, Patients will receive capivasertib PO BID on days 1-4. In arm 4, Patients will receive abemaciclib PO Q12H.


Patients Must Have Histologically Proven Intracranial Meningioma As Documented By Central Pathology Review. Presence Of Smo, Ptch1, Nf2, Cdkn2a, Akt1, Pik3ca, Pten Mutations, Cdkn2a Copy Number Loss, Cdk4, Cdk6, Ccnd1, Ccnd2, Ccnd3, Or Ccne1 Copy Number Gain In Tumor Sample As Documented Specifically By The Central Laboratory, Regardless Of Whether Prior Genotype Testing Outside Of The Central Laboratory Was Performed. Measurable Disease Present. Absolute Neutrophil Count (Anc) >= 1,500/Mm^3. Platelet Count >= 100,000/Mm^3. Creatinine Or =< 1.5 Mg/Dl X Upper Limit Of Normal (Uln) Or Calculated (Calc.) Creatinine Clearance > 50 Ml/Min. Urine Protein:Creatinine Ratio (Upc) =< 45 Mg/Mmol. Total Bilirubin =< 1.5 X Upper Limit Of Normal (Uln); Except In Case Of Gilbert's Disease. Aspartate Aminotransferase (Ast)/Alanine Aminotransferase (Alt) =< 2.5 X Uln. Sodium, Potassium, Total Calcium (Corrected For Serum Albumin) & Phosphorus Within Normal Limits Per Institutional Guidelines. Qtcf < 450 Msec. Mean Resting Heart Rate (Determined From Ekg) 50-100 Beats Per Minute (Bmp). No Uncontrolled Medical Comorbidities Per Investigator Discretion. For Patients With Nf2 Or Smo/Ptch1 Mutations: No Uncontrolled Diabetes Defined As A Known Diabetic With Hba1c > 7.5 Or Fasting Glucose > 140 Mg/Dl. No Past Medical History Of Interstitial Lung Disease, Drug-Induced Interstitial Lung Disease, Radiation Pneumonitis Which Required Steroid Treatment, Or Any Evidence Of Clinically Active Interstitial Lung Disease. No Previous Allogeneic Bone Marrow Transplant. No Known Immunodeficiency Syndrome. No Refractory Nausea And Vomiting, Chronic Gastrointestinal Diseases, Inability To Swallow The Formulated Product Or Previous Significant Bowel Resection That Would Preclude Adequate Absorption Of Capivasertib. No Current Disease Or Condition Known To Interfere With Absorption, Distribution, Metabolism, Or Excretion Of Drugs. No Unresolved Toxicities From Prior Therapy Greater Than Common Terminology Criteria For Adverse Events (Ctcae) Grade 1 At The Time Of Registration.


A071401, Cancer, Brain, Smo/Akt/Nf2 Mutation, Meningioma

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