Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: A report from the 11715 study group

David F. McDermott, Jeffrey A. Sosman, Rene Gonzalez, F. Stephen Hodi, Gerald P. Linette, Jon Richards, James W. Jakub, Muralidhar Beeram, Stefano Tarantolo, Sanjiv Agarwala, Gary Frenette, Igor Puzanov, Lee D Cranmer, Karl Lewis, John Kirkwood, J. Michael White, Chenghua Xia, Kiran Patel, Evan M Hersh

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Abstract

Purpose: This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma. Patients and Methods: This randomized, double-blind, placebo-controlled, multicenter study enrolled chemotherapy-naïve patients with stage III (unresectable) or IV melanoma. A total of 101 patients received placebo plus dacarbazine (n = 50) or sorafenib plus dacarbazine (n = 51). On day 1 of a 21-day cycle, patients received intravenous dacarbazine 1,000 mg/m2 for a maximum of 16 cycles. Oral sorafenib 400 mg or placebo was administered twice a day continuously. The primary end point was progressionfree survival (PFS) by independent assessment. Secondary and tertiary end points included time to progression (TTP), response rate, and overall survival (OS). Results: Median PFS in the sorafenib plus dacarbazine arm was 21.1 weeks versus 11.7 weeks in the placebo plus dacarbazine arm (hazard ratio [HR], 0.665; P = .068). There were statistically significant improvements in PFS rates at 6 and 9 months, and in TTP (median, 21.1 v 11.7 weeks; HR, 0.619) in favor of the sorafenib plus dacarbazine arm. No difference in OS was observed (median, 51.3 v 45.6 weeks in the placebo plus dacarbazine and sorafenib plus dacarbazine arms, respectively; HR, 1.022). The regimen was well tolerated and had a manageable toxicity profile. Conclusion: Sorafenib plus dacarbazine was well tolerated in patients with advanced melanoma and yielded an encouraging improvement in PFS. Based on these findings, additional studies with the combination are warranted in this patient population.

Original languageEnglish (US)
Pages (from-to)2178-2185
Number of pages8
JournalJournal of Clinical Oncology
Volume26
Issue number13
DOIs
StatePublished - 2008
Externally publishedYes

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Dacarbazine
Melanoma
Placebos
Survival
Survival Rate
sorafenib
Multicenter Studies
Safety
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma : A report from the 11715 study group. / McDermott, David F.; Sosman, Jeffrey A.; Gonzalez, Rene; Hodi, F. Stephen; Linette, Gerald P.; Richards, Jon; Jakub, James W.; Beeram, Muralidhar; Tarantolo, Stefano; Agarwala, Sanjiv; Frenette, Gary; Puzanov, Igor; Cranmer, Lee D; Lewis, Karl; Kirkwood, John; White, J. Michael; Xia, Chenghua; Patel, Kiran; Hersh, Evan M.

In: Journal of Clinical Oncology, Vol. 26, No. 13, 2008, p. 2178-2185.

Research output: Contribution to journalArticle

McDermott, DF, Sosman, JA, Gonzalez, R, Hodi, FS, Linette, GP, Richards, J, Jakub, JW, Beeram, M, Tarantolo, S, Agarwala, S, Frenette, G, Puzanov, I, Cranmer, LD, Lewis, K, Kirkwood, J, White, JM, Xia, C, Patel, K & Hersh, EM 2008, 'Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: A report from the 11715 study group', Journal of Clinical Oncology, vol. 26, no. 13, pp. 2178-2185. https://doi.org/10.1200/JCO.2007.14.8288
McDermott, David F. ; Sosman, Jeffrey A. ; Gonzalez, Rene ; Hodi, F. Stephen ; Linette, Gerald P. ; Richards, Jon ; Jakub, James W. ; Beeram, Muralidhar ; Tarantolo, Stefano ; Agarwala, Sanjiv ; Frenette, Gary ; Puzanov, Igor ; Cranmer, Lee D ; Lewis, Karl ; Kirkwood, John ; White, J. Michael ; Xia, Chenghua ; Patel, Kiran ; Hersh, Evan M. / Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma : A report from the 11715 study group. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 13. pp. 2178-2185.
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abstract = "Purpose: This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma. Patients and Methods: This randomized, double-blind, placebo-controlled, multicenter study enrolled chemotherapy-na{\"i}ve patients with stage III (unresectable) or IV melanoma. A total of 101 patients received placebo plus dacarbazine (n = 50) or sorafenib plus dacarbazine (n = 51). On day 1 of a 21-day cycle, patients received intravenous dacarbazine 1,000 mg/m2 for a maximum of 16 cycles. Oral sorafenib 400 mg or placebo was administered twice a day continuously. The primary end point was progressionfree survival (PFS) by independent assessment. Secondary and tertiary end points included time to progression (TTP), response rate, and overall survival (OS). Results: Median PFS in the sorafenib plus dacarbazine arm was 21.1 weeks versus 11.7 weeks in the placebo plus dacarbazine arm (hazard ratio [HR], 0.665; P = .068). There were statistically significant improvements in PFS rates at 6 and 9 months, and in TTP (median, 21.1 v 11.7 weeks; HR, 0.619) in favor of the sorafenib plus dacarbazine arm. No difference in OS was observed (median, 51.3 v 45.6 weeks in the placebo plus dacarbazine and sorafenib plus dacarbazine arms, respectively; HR, 1.022). The regimen was well tolerated and had a manageable toxicity profile. Conclusion: Sorafenib plus dacarbazine was well tolerated in patients with advanced melanoma and yielded an encouraging improvement in PFS. Based on these findings, additional studies with the combination are warranted in this patient population.",
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T1 - Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma

T2 - A report from the 11715 study group

AU - McDermott, David F.

AU - Sosman, Jeffrey A.

AU - Gonzalez, Rene

AU - Hodi, F. Stephen

AU - Linette, Gerald P.

AU - Richards, Jon

AU - Jakub, James W.

AU - Beeram, Muralidhar

AU - Tarantolo, Stefano

AU - Agarwala, Sanjiv

AU - Frenette, Gary

AU - Puzanov, Igor

AU - Cranmer, Lee D

AU - Lewis, Karl

AU - Kirkwood, John

AU - White, J. Michael

AU - Xia, Chenghua

AU - Patel, Kiran

AU - Hersh, Evan M

PY - 2008

Y1 - 2008

N2 - Purpose: This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma. Patients and Methods: This randomized, double-blind, placebo-controlled, multicenter study enrolled chemotherapy-naïve patients with stage III (unresectable) or IV melanoma. A total of 101 patients received placebo plus dacarbazine (n = 50) or sorafenib plus dacarbazine (n = 51). On day 1 of a 21-day cycle, patients received intravenous dacarbazine 1,000 mg/m2 for a maximum of 16 cycles. Oral sorafenib 400 mg or placebo was administered twice a day continuously. The primary end point was progressionfree survival (PFS) by independent assessment. Secondary and tertiary end points included time to progression (TTP), response rate, and overall survival (OS). Results: Median PFS in the sorafenib plus dacarbazine arm was 21.1 weeks versus 11.7 weeks in the placebo plus dacarbazine arm (hazard ratio [HR], 0.665; P = .068). There were statistically significant improvements in PFS rates at 6 and 9 months, and in TTP (median, 21.1 v 11.7 weeks; HR, 0.619) in favor of the sorafenib plus dacarbazine arm. No difference in OS was observed (median, 51.3 v 45.6 weeks in the placebo plus dacarbazine and sorafenib plus dacarbazine arms, respectively; HR, 1.022). The regimen was well tolerated and had a manageable toxicity profile. Conclusion: Sorafenib plus dacarbazine was well tolerated in patients with advanced melanoma and yielded an encouraging improvement in PFS. Based on these findings, additional studies with the combination are warranted in this patient population.

AB - Purpose: This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma. Patients and Methods: This randomized, double-blind, placebo-controlled, multicenter study enrolled chemotherapy-naïve patients with stage III (unresectable) or IV melanoma. A total of 101 patients received placebo plus dacarbazine (n = 50) or sorafenib plus dacarbazine (n = 51). On day 1 of a 21-day cycle, patients received intravenous dacarbazine 1,000 mg/m2 for a maximum of 16 cycles. Oral sorafenib 400 mg or placebo was administered twice a day continuously. The primary end point was progressionfree survival (PFS) by independent assessment. Secondary and tertiary end points included time to progression (TTP), response rate, and overall survival (OS). Results: Median PFS in the sorafenib plus dacarbazine arm was 21.1 weeks versus 11.7 weeks in the placebo plus dacarbazine arm (hazard ratio [HR], 0.665; P = .068). There were statistically significant improvements in PFS rates at 6 and 9 months, and in TTP (median, 21.1 v 11.7 weeks; HR, 0.619) in favor of the sorafenib plus dacarbazine arm. No difference in OS was observed (median, 51.3 v 45.6 weeks in the placebo plus dacarbazine and sorafenib plus dacarbazine arms, respectively; HR, 1.022). The regimen was well tolerated and had a manageable toxicity profile. Conclusion: Sorafenib plus dacarbazine was well tolerated in patients with advanced melanoma and yielded an encouraging improvement in PFS. Based on these findings, additional studies with the combination are warranted in this patient population.

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