Randomized phase II trial of sorafenib with temsirolimus or tipifarnib in untreated metastatic melanoma (S0438)

Kim A. Margolin*, James Moon, Lawrence E. Flaherty, Christopher D. Lao, Wallace L. Akerley, Megan Othus, Jeffrey A. Sosman, John M. Kirkwood, Vernon K. Sondak

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Purpose: Signaling pathway stimulation by activating mutations of oncogenes occurs in mostmelanomas and can provide excellent targets for therapy, but the short-term therapeutic success is limited by intrinsic and acquired resistance. The mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT/mTOR pathways are activated in most cutaneous melanomas. The purpose of this trial was to prospectively evaluate 2 molecularly targeted drug combinations in patients with untreated metastatic melanoma. Experimental Design: This randomized phase II study enrolled patients between May 2008 and November 2009 with nonocular melanoma, no prior systemic chemotherapy, and no history of brain metastasis. Arm A received oral sorafenib 200 mg twice daily plus i.v. temsirolimus 25 mg weekly; and arm B received oral sorafenib 400 mg every morning, 200 mg every night daily plus oral tipifarnib 100 mg twice daily, 3 weeks of every 4. The primary objectives were to evaluate progression-free survival (PFS), objective response rate, and toxicity for the 2 regimens. Results: On arm A (63 evaluable patients), the median PFS was 2.1 months and median overall survival (OS) was 7 months. Three patients achieved partial response (PR). Thirty-nine evaluable patients were accrued to arm B, which closed after first-stage accrual; the median PFS was 1.8 months and OS was 7 months, with 1 patient achieving PR. Conclusions: The combinations of molecularly targeted agents tested did not show sufficient activity to justify further use. Newer agents and improved patient selection by characterization of the molecular targets in individual tumors show great promise and should be incorporated into future studies, along with appropriate laboratory correlates.

Original languageEnglish (US)
Pages (from-to)1129-1137
Number of pages9
JournalClinical Cancer Research
Issue number4
StatePublished - Feb 15 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Randomized phase II trial of sorafenib with temsirolimus or tipifarnib in untreated metastatic melanoma (S0438)'. Together they form a unique fingerprint.

Cite this