A Phase I Study of an MPS1 Inhibitor (BAY 1217389) in Combination with Paclitaxel Using a Novel Randomized Continual Reassessment Method for Dose Escalation.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 12 2021
01 12 2021
Historique:
received:
29
10
2020
revised:
05
01
2021
accepted:
09
09
2021
pubmed:
15
9
2021
medline:
8
4
2022
entrez:
14
9
2021
Statut:
ppublish
Résumé
Monopolar spindle 1 (MPS1) kinase inhibitor, BAY 1217389 (BAY) synergizes with paclitaxel. This phase I study assessed the combination of BAY with paclitaxel using a novel randomized continuous reassessment method (rCRM) to improve dose determination. Patients with solid tumors were randomized to receive oral BAY (twice daily 2-days-on/5-days-off) with weekly paclitaxel (90 mg/m In total, 75 patients were enrolled. The main dose-limiting toxicities were hematologic toxicities (55.6%). The MTD of BAY was established at 64 mg twice daily with paclitaxel. Inclusion of a control arm enabled the definitive attribution of grade ≥3 neutropenia to higher BAY exposure [AUC The combination of BAY with paclitaxel was associated with considerable toxicity without a therapeutic window. However, the use of the rCRM design enabled us to determine the exposure-toxicity relation for BAY. Therefore, we propose that the rCRM could improve dose determination in phase I trials that combine agents with overlapping toxicities.
Identifiants
pubmed: 34518310
pii: 1078-0432.CCR-20-4185
doi: 10.1158/1078-0432.CCR-20-4185
doi:
Substances chimiques
Paclitaxel
P88XT4IS4D
Types de publication
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6366-6375Commentaires et corrections
Type : ErratumIn
Informations de copyright
©2021 American Association for Cancer Research.
Références
Bayat Mokhtari R, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, et al. Combination therapy in combating cancer. Oncotarget. 2017;8:38022–43.
Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109–19.
Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB, et al. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016;375:23–34.
Chan A, Miles DW, Pivot X. Bevacizumab in combination with taxanes for the first-line treatment of metastatic breast cancer. Ann Oncol. 2010;21:2305–15.
Dong L, Zhu LN, Xie BJ, Li JB, Ding T, Jiang YF, et al. Comparative effectiveness of taxane-containing regimens for treatment of HER2-negative metastatic breast cancer: a network meta-analysis. Pharmacotherapy. 2019;39:1126–36.
Xie BJ, Zhu LN, Ma C, Li JB, Dong L, Zhu ZN, et al. A network meta-analysis on the efficacy of HER2-targeted agents in combination with taxane-containing regimens for treatment of HER2-positive metastatic breast cancer. Breast Cancer. 2020;27:186–96.
Ghersi D, Willson ML, Chan MM, Simes J, Donoghue E, Wilcken N. Taxane-containing regimens for metastatic breast cancer. Cochrane Database Syst Rev. 2015;2015:CD003366.
Ghersi D, Wilcken N, Simes RJ. A systematic review of taxane-containing regimens for metastatic breast cancer. Br J Cancer. 2005;93:293–301.
Maher JF, Villalona-Calero MA. Taxanes and capecitabine in combination: rationale and clinical results. Clin Breast Cancer. 2002;2:287–93.
Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007;608:1–22.
Wengner AM, Siemeister G, Koppitz M, Schulze V, Kosemund D, Klar U, et al. Novel Mps1 kinase inhibitors with potent antitumor activity. Mol Cancer Ther. 2016;15:583–92.
Jemaa M, Galluzzi L, Kepp O, Senovilla L, Brands M, Boemer U, et al. Characterization of novel MPS1 inhibitors with preclinical anticancer activity. Cell Death Differ. 2013;20:1532–45.
Schulze VK, Klar U, Kosemund D, Wengner AM, Siemeister G, Stockigt D, et al. Treating cancer by spindle assembly checkpoint abrogation: discovery of two clinical candidates, BAY 1161909 and BAY 1217389, targeting MPS1 kinase. J Med Chem. 2020;63:8025–42.
Beuselinck B, Wildiers H, Wynendaele W, Dirix L, Kains JP, Paridaens R. Weekly paclitaxel versus weekly docetaxel in elderly or frail patients with metastatic breast carcinoma: a randomized phase-II study of the Belgian Society of Medical Oncology. Crit Rev Oncol Hematol. 2010;75:70–7.
Gradishar WJ, Kaklamani V, Sahoo TP, Lokanatha D, Raina V, Bondarde S, et al. A double-blind, randomised, placebo-controlled, phase 2b study evaluating sorafenib in combination with paclitaxel as a first-line therapy in patients with HER2-negative advanced breast cancer. Eur J Cancer. 2013;49:312–22.
Horiguchi J, Rai Y, Tamura K, Taki T, Hisamatsu K, Ito Y, et al. Phase II study of weekly paclitaxel for advanced or metastatic breast cancer in Japan. Anticancer Res. 2009;29:625–30.
Klaassen U, Wilke H, Strumberg D, Eberhardt W, Korn M, Seeber S. Phase I study with a weekly 1 h infusion of paclitaxel in heavily pretreated patients with metastatic breast and ovarian cancer. Eur J Cancer. 1996;32A:547–9.
Lombardi D, Crivellari D, Scuderi C, Magri MD, Spazzapan S, Sorio R, et al. Long-term, weekly one-hour infusion of paclitaxel in patients with metastatic breast cancer: a phase II monoinstitutional study. Tumori. 2004;90:285–8.
Nishimura R, Ogawa T, Kato M, Tanaka M, Hamada Y, Shibata T, et al. Weekly paclitaxel in the treatment of advanced or metastatic breast cancer previously treated or not treated with docetaxel: a phase II study. Chemotherapy. 2005;51:126–31.
Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard I, Piperno-Neumann S, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study. J Clin Oncol. 2008;26:5269–74.
Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001;19:4216–23.
Sato K, Inoue K, Saito T, Kai T, Mihara H, Okubo K, et al. Multicenter phase II trial of weekly paclitaxel for advanced or metastatic breast cancer: the Saitama Breast Cancer Clinical Study Group (SBCCSG-01). Jpn J Clin Oncol. 2003;33:371–6.
Taguchi T, Aihara T, Takatsuka Y, Shin E, Motomura K, Inaji H, et al. Phase II study of weekly paclitaxel for docetaxel-resistant metastatic breast cancer in Japan. Breast J. 2004;10:509–13.
ten Tije AJ, Smorenburg CH, Seynaeve C, Sparreboom A, Schothorst KL, Kerkhofs LG, et al. Weekly paclitaxel as first-line chemotherapy for elderly patients with metastatic breast cancer. A multicentre phase II trial. Eur J Cancer. 2004;40:352–7.
Dejardin D, Lesaffre E, Hamberg P, Verweij J. A randomized phase I Bayesian dose escalation design for the combination of anti-cancer drugs. Pharm Stat. 2014;13:196–207.
Koopmeiners JS, Wey A. The randomized CRM: an approach to overcoming the long-memory property of the CRM. J Biopharm Stat. 2017;27:1028–42.
2001.
2011.
Danesi R, Innocenti F, Fogli S, Gennari A, Baldini E, Di Paolo A, et al. Pharmacokinetics and pharmacodynamics of combination chemotherapy with paclitaxel and epirubicin in breast cancer patients. Br J Clin Pharmacol. 2002;53:508–18.
Wandel C, Kim RB, Stein CM. “Inactive” excipients such as Cremophor can affect in vivo drug disposition. Clin Pharmacol Ther. 2003;73:394–6.
Berman E, Nicolaides M, Maki RG, Fleisher M, Chanel S, Scheu K, et al. Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med. 2006;354:2006–13.
Oronsky B, Caroen S, Oronsky A, Dobalian VE, Oronsky N, Lybeck M, et al. Electrolyte disorders with platinum-based chemotherapy: mechanisms, manifestations and management. Cancer Chemother Pharmacol. 2017;80:895–907.
Owonikoko TK, Dahlberg SE, Khan SA, Gerber DE, Dowell J, Moss RA, et al. A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: a trial of the ECOG-ACRIN Cancer Research Group (E2511). Lung Cancer. 2015;89:66–70.
Mizugaki H, Yamamoto N, Nokihara H, Fujiwara Y, Horinouchi H, Kanda S, et al. A phase 1 study evaluating the pharmacokinetics and preliminary efficacy of veliparib (ABT-888) in combination with carboplatin/paclitaxel in Japanese subjects with non-small cell lung cancer (NSCLC). Cancer Chemother Pharmacol. 2015;76:1063–72.
Kanjanapan Y, Day D, Butler MO, Wang L, Joshua AM, Hogg D, et al. Delayed immune-related adverse events in assessment for dose-limiting toxicity in early phase immunotherapy trials. Eur J Cancer. 2019;107:1–7.