J1271: A Randomized Three Arm Phase II Study of (1) Everolimus, (2)Estrogen Deprivation Therapy (EDT) with Leuprolide + Letrozole and (3) Everolimus + EDT in Patients with Unresectable Fibrolamellar Hepatocellular Carcinoma (FLL-HCC)
â?¢Progression-free survival at 6 months (PFS6) â?¢To evaluate median progression-free survival â?¢To evaluate median overall survival â?¢To evaluate objective response rate by RECIST 1.1 guidelines â?¢To evaluate rate of conversion to resectable status â?¢To evaluate safety/toxicity profiles â?¢To evaluate correlative tissue and serum biomarkers
1.Subjects greater than or equal to 12 years old 2.Pathologically confirmed diagnosis of advanced and/or unresectable FLL_HCC 3.ECOG performance status 0-2; Lansky performance score of greater than or equal to 60% for subject 12-16 years of age 4.Adequate hematologic, renal and hepatic function 5.Measurable disease 6.Prior systemic therapy is allowed 7.Concurrent antiviral therapy for hepatitis B is permitted 8.Must have negative pregnancy result for women of child bearing potential 9.Must have completed all anticancer therapy greater than 4 weeks before the start of study 10.No major surgery or significant traumatic injury within 4 weeks of start of study drug 11.No systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed 12.No concurrent oral contraceptive use or hormonal replacement therapy 13.No use of an aromatase inhibitor, GnRH agonist and/or tamoxifen within the past 30 days. Subjects previously on fulvestrant or a q3 month GnRH agonist must have discontinued these medications for at least 3 months 14.No concurrent use of potent CYP3A4 and/or P-glycoprotein inhibitors or potent CYP3A4 inducers 15.No investigational drug received within one month of study enrollment 16.No uncontrolled brain or leptomeningeal mets 17.No severe, uncontrolled medical conditions 18.No psychiatric illness/social situations that would limit compliance with the study 19.No subjects that have received any form of transplant and that are on any form of immunosuppressive therapy. Transplanted subject that are off immunosuppressive therapy for at least 4 weeks are allowed on study 20.No know HIV positive 21.No immunization with a live vaccine less than 1 week of initiating study therapy or during therapy 22.BSA canâ??t be less than 1m2
This is a multi-institutional randomization three arms phase II clinical trial, consisting of two parts. In part 1 of this study, subjects with advanced (recurrent or metastatic), unresectable FLL-HCC will be randomized to one of three arms: Arm A; Arm B; or Arm C. Upon disease progression, subjects in Arm A or Arm B may proceed to Part 2 of the study in which they will receive combination therapy.
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