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A phase II trial of RAD001 in patients (Pts) with metastatic renal cell carcinoma (MRCC)
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2007
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PathologyTumor BiologyOncologyGenitourinary CancerCancer Cell BiologyRadiopharmaceutical TherapyAnti-tumor ActivityRadiation OncologyCancer ResearchMolecular OncologyPhase Ii TrialResponse RateCancer TreatmentPharmacologyTumor ResponseUrologyImmune Checkpoint InhibitorTumor SuppressorMedicine
5107 Background: RAD001 is an oral mammalian target of Rapamycin (mTOR) inhibitor. Three mechanisms of anti-tumor activity; shuts down tumor response to nutrients and growth factors; cell cycle arrest at late G1 and anti-angiogenesis via VEGF. Molecular alterations in the mTOR modular pathway increase sensitivity in PTEN deficient tumors such as RCC. Endpoints: time-to-progression (TTP), response rate (RR), overall survival (OS), toxicity, and to assess changes in metabolic imaging utilizing CT-PET. Methods: Eligibility included; predominant clear cell, progressive measurable MRCC, adequate organ/marrow function, zubrod performance status (ZPS) = 2, no more than 1 prior therapy, and no active CNS involvement. RAD001 is given orally at a dose of 10mg daily without an interruption (28-day cycle), with dose modifications for toxicity. Re-evaluation was assessed every 2 cycles (8 weeks). RECIST criteria is utilized. TTP and OS are determined from entry into the study. Results: 41 pts have been enrolled. 37 pts are evaluable for response/toxicity. 2 pts toxicity only. 2 pts screened failures. 31 were male/8 female, median age 60 (38–80) years. 31 pts received prior therapy. 23 pts had a ZPS of 0, 13 /1 and 3/2. Sites of disease included; lung, nodal, liver, bone, adrenal, and kidney. 9 pts had 1 metastatic site, 17 pts/2 and 13 pts/3 or more. 15 pts continue to receive RAD001. 12 pts had partial responses, 19 pts were stable for 3+ months. Median duration of therapy is 8+ (range 01–20+) months. Treatment related adverse events; mucositis, skin rash, pneumonitis, hypophosphatemia, hyperglycemia, hypertriglyceridemia, hypercholesterolemia, thrombocytopenia, anemia and elevated LFTs. PET scans have demonstrated decreased metabolic activity in responding or stable pts. Median overall survival is 11.5+ months (range 01–20+). Conclusion: RAD001 has promising anti-tumor activity in pts with MRCC demonstrated by partial response rate. Anti-tumor activity is further suggested by prolonged TTP =3 months. Anti-tumor activity, toxicity and metabolic imaging correlation will be presented. An additional 40 pts who failed prior sunitinib or sorafenib therapy are being enrolled. No significant financial relationships to disclose.