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Phase I/II study of mocetinostat in combination with gemcitabine for patients with advanced pancreatic cancer and other advanced solid tumors.

Publication ,  Journal Article
Chan, E; Chiorean, EG; O'Dwyer, PJ; Gabrail, NY; Alcindor, T; Potvin, D; Chao, R; Hurwitz, H
Published in: Cancer Chemother Pharmacol
February 2018

PURPOSE: To evaluate the safety and efficacy of mocetinostat (a Class I/IV HDAC inhibitor) in combination with gemcitabine in patients with solid tumors, including pancreatic cancer. METHODS: In this open-label, non-randomized Phase I/II study (NCT00372437) sequential cohorts of patients with solid tumors received gemcitabine (1000 mg/m2, day 1 of three consecutive weeks, 4-week cycles) and oral mocetinostat [50-110 mg, three times per week (TIW)]. The maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) was determined based on dose-limiting toxicities in Cycle 1 (Phase I study). The MTD/RP2D was further evaluated in patients with advanced pancreatic cancer (Phase II study) using a two-stage design. The Phase II primary endpoint was overall response rate (ORR). RESULTS: Forty-eight patients were enrolled into the Phase I (n = 25) and Phase II (n = 23) studies. In the Phase I study, the MTD/RP2D was mocetinostat 90 mg TIW + gemcitabine 1000 mg/m2. Grade ≥ 3 treatment-related adverse events (AEs) were reported by 81% of all patients, the most frequent being fatigue (38%) and thrombocytopenia (19%). The ORR was 11% in the Phase I study (n = 2 patients with pancreatic cancer, responses lasting for 16.8 and 4.0 months, respectively). As no responses were seen in the Phase II cohort, the study was terminated. CONCLUSIONS: Mocetinostat TIW in combination with gemcitabine was associated with significant toxicities in patients with advanced pancreatic cancer. The level of clinical activity of this treatment combination was not considered high enough to merit further testing in this setting.

Duke Scholars

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

February 2018

Volume

81

Issue

2

Start / End Page

355 / 364

Location

Germany

Related Subject Headings

  • Treatment Outcome
  • Pyrimidines
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Humans
  • Histone Deacetylase Inhibitors
 

Citation

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Chan, E., Chiorean, E. G., O’Dwyer, P. J., Gabrail, N. Y., Alcindor, T., Potvin, D., … Hurwitz, H. (2018). Phase I/II study of mocetinostat in combination with gemcitabine for patients with advanced pancreatic cancer and other advanced solid tumors. Cancer Chemother Pharmacol, 81(2), 355–364. https://doi.org/10.1007/s00280-017-3494-3
Chan, Emily, E Gabriela Chiorean, Peter J. O’Dwyer, Nashat Y. Gabrail, Thierry Alcindor, Diane Potvin, Richard Chao, and Herbert Hurwitz. “Phase I/II study of mocetinostat in combination with gemcitabine for patients with advanced pancreatic cancer and other advanced solid tumors.Cancer Chemother Pharmacol 81, no. 2 (February 2018): 355–64. https://doi.org/10.1007/s00280-017-3494-3.
Chan E, Chiorean EG, O’Dwyer PJ, Gabrail NY, Alcindor T, Potvin D, et al. Phase I/II study of mocetinostat in combination with gemcitabine for patients with advanced pancreatic cancer and other advanced solid tumors. Cancer Chemother Pharmacol. 2018 Feb;81(2):355–64.
Chan, Emily, et al. “Phase I/II study of mocetinostat in combination with gemcitabine for patients with advanced pancreatic cancer and other advanced solid tumors.Cancer Chemother Pharmacol, vol. 81, no. 2, Feb. 2018, pp. 355–64. Pubmed, doi:10.1007/s00280-017-3494-3.
Chan E, Chiorean EG, O’Dwyer PJ, Gabrail NY, Alcindor T, Potvin D, Chao R, Hurwitz H. Phase I/II study of mocetinostat in combination with gemcitabine for patients with advanced pancreatic cancer and other advanced solid tumors. Cancer Chemother Pharmacol. 2018 Feb;81(2):355–364.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

February 2018

Volume

81

Issue

2

Start / End Page

355 / 364

Location

Germany

Related Subject Headings

  • Treatment Outcome
  • Pyrimidines
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Humans
  • Histone Deacetylase Inhibitors