Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib

• Drug: Sorafenib
  
  Subjects randomized to arm B will take sorafenib 400 mg (2 x 200 mg tablets) PO, BID (total daily dose of 800 mg).
• Drug: temsirolimus (Torisel)
  
  Subjects randomized to arm A will receive temsirolimus (Torisel) 25 mg via IV infusion once weekly. This infusion is to be administered over a 30-60 minute period. Subjects are to be pre-treated with 25-50 mg IV diphenhydramine (or comparable IV antihistamine) approximately 30 minutes before temsirolimus infusion.

• Experimental: 1
  
  Intervention: Drug: Sorafenib
• Experimental: 2
  
  Intervention: Drug: temsirolimus (Torisel)

• de Velasco G, McKay RR, Lin X, Moreira RB, Simantov R, Choueiri TK. Comprehensive Analysis of Survival Outcomes in Non-Clear Cell Renal Cell Carcinoma Patients Treated in Clinical Trials. Clin Genitourin Cancer. 2017 Dec;15(6):652-660.e1. doi: 10.1016/j.clgc.2017.03.004. Epub 2017 Mar 21.
• Grünwald V, Lin X, Kalanovic D, Simantov R. Early Tumour Shrinkage: A Tool for the Detection of Early Clinical Activity in Metastatic Renal Cell Carcinoma. Eur Urol. 2016 Dec;70(6):1006-1015. doi: 10.1016/j.eururo.2016.05.010. Epub 2016 May 26.
• Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, Senico P, Niethammer A, Lu DR, Hariharan S, Motzer RJ. Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Mar 10;32(8):760-7. doi: 10.1200/JCO.2013.50.3961. Epub 2013 Dec 2.

Inclusion Criteria:

• Histologically confirmed diagnosis of mRCC (regardless of histology or nephrectomy status) with well-documented Radiological PD by RECIST criteria or clinical PD as judged by the investigator while receiving first-line sunitinib therapy. Subjects must have at least 1 cycle of sunitinib therapy (minimum of four weeks continuously).
• At time of randomization, at least 2 weeks since prior treatment with sunitinib, palliative radiation therapy, and/or surgery.

• At time of randomization, there must be at least 1 measurable lesion per RECIST. Lesions that have been previously irradiated or embolized cannot be selected as target lesions.

  • More criteria apply

Exclusion Criteria:

• Metastatic CNS from RCC.
• Subjects who discontinued Sutent therapy due specifically to intolerance.
• Prior systemic therapy for mRCC other than sunitinib.

• Active ketonuria, secondary to poorly controlled diabetes mellitus

  • More criteria apply