SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma

Scott M. Schuetze, J. Kyle Wathen, David R. Lucas, Edwin Choy, Brian L. Samuels, Arthur P. Staddon, Kristen N. Ganjoo, Margaret Von Mehren, Warren A. Chow, David M. Loeb, Hussein A. Tawbi, Daniel A. Rushing, Shreyaskumar R. Patel, Dafydd G. Thomas, Rashmi Chugh, Denise K. Reinke, Laurence H. Baker

Research output: Contribution to journalArticle

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Abstract

BACKGROUND Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma. METHODS Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ≥6 months) with a target of ≥25%. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a <1% chance the CBR was ≥25%. RESULTS A total of 200 patients were enrolled. Accrual was stopped early in 5 cohorts because of low CBR. The leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ≥25% in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36% of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11% of patients. CONCLUSIONS Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity.

Original languageEnglish (US)
Pages (from-to)868-874
Number of pages7
JournalCancer
Volume122
Issue number6
DOIs
StatePublished - Mar 15 2016
Externally publishedYes

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Sarcoma
Leiomyosarcoma
Dasatinib
Rhabdomyosarcoma
Disease-Free Survival
Survival

Keywords

  • adaptive
  • Bayesian
  • Choi
  • dasatinib
  • phase 2
  • sarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Schuetze, S. M., Wathen, J. K., Lucas, D. R., Choy, E., Samuels, B. L., Staddon, A. P., ... Baker, L. H. (2016). SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma. Cancer, 122(6), 868-874. https://doi.org/10.1002/cncr.29858

SARC009 : Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma. / Schuetze, Scott M.; Wathen, J. Kyle; Lucas, David R.; Choy, Edwin; Samuels, Brian L.; Staddon, Arthur P.; Ganjoo, Kristen N.; Von Mehren, Margaret; Chow, Warren A.; Loeb, David M.; Tawbi, Hussein A.; Rushing, Daniel A.; Patel, Shreyaskumar R.; Thomas, Dafydd G.; Chugh, Rashmi; Reinke, Denise K.; Baker, Laurence H.

In: Cancer, Vol. 122, No. 6, 15.03.2016, p. 868-874.

Research output: Contribution to journalArticle

Schuetze, SM, Wathen, JK, Lucas, DR, Choy, E, Samuels, BL, Staddon, AP, Ganjoo, KN, Von Mehren, M, Chow, WA, Loeb, DM, Tawbi, HA, Rushing, DA, Patel, SR, Thomas, DG, Chugh, R, Reinke, DK & Baker, LH 2016, 'SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma', Cancer, vol. 122, no. 6, pp. 868-874. https://doi.org/10.1002/cncr.29858
Schuetze SM, Wathen JK, Lucas DR, Choy E, Samuels BL, Staddon AP et al. SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma. Cancer. 2016 Mar 15;122(6):868-874. https://doi.org/10.1002/cncr.29858
Schuetze, Scott M. ; Wathen, J. Kyle ; Lucas, David R. ; Choy, Edwin ; Samuels, Brian L. ; Staddon, Arthur P. ; Ganjoo, Kristen N. ; Von Mehren, Margaret ; Chow, Warren A. ; Loeb, David M. ; Tawbi, Hussein A. ; Rushing, Daniel A. ; Patel, Shreyaskumar R. ; Thomas, Dafydd G. ; Chugh, Rashmi ; Reinke, Denise K. ; Baker, Laurence H. / SARC009 : Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma. In: Cancer. 2016 ; Vol. 122, No. 6. pp. 868-874.
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abstract = "BACKGROUND Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma. METHODS Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ≥6 months) with a target of ≥25{\%}. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a <1{\%} chance the CBR was ≥25{\%}. RESULTS A total of 200 patients were enrolled. Accrual was stopped early in 5 cohorts because of low CBR. The leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ≥25{\%} in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36{\%} of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11{\%} of patients. CONCLUSIONS Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity.",
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AU - Choy, Edwin

AU - Samuels, Brian L.

AU - Staddon, Arthur P.

AU - Ganjoo, Kristen N.

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N2 - BACKGROUND Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma. METHODS Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ≥6 months) with a target of ≥25%. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a <1% chance the CBR was ≥25%. RESULTS A total of 200 patients were enrolled. Accrual was stopped early in 5 cohorts because of low CBR. The leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ≥25% in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36% of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11% of patients. CONCLUSIONS Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity.

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