Clinical trial NCT02448589: An Investigation of TAS-119 Monotherapy
Official title: A Phase I, Open-Label, Non-Randomized, Dose-Escalating Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of TAS-119 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Advanced Solid Tumors
Dose Escalation
Dose Expansion
MTD
TAS-119
Aurora A Kinase Inhibitor
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2015-05-19
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Phase 1, Open-Label, Non-Randomized, Dose-Escalating Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of TAS-119 in Patients with Advanced Solid Tumors.

Detailed description: This is a Phase 1, open-label, non-randomized, dose escalation study of TAS-119 evaluating the safety, tolerability, PK, pharmacogenomics, pharmacodynamics, and preliminary antitumour activity in patients with advanced and unresectable solid tumours. The study will evaluate TAS-119 monotherapy, employing two sequential phases.

* A Dose Escalation Phase
* An Expansion Phase

Eligibility criteria: Inclusion criteria include the following:

1. Is a male or female, ≥ 18 years of age, who has provided written informed consent.
2. Has histologically or cytologically confirmed advanced, unresectable, metastatic solid tumor(s) for which the patients have no available therapy likely to provide clinical benefit.
3. Must have an archival FFPE tumor sample available, to be provided to the Sponsor upon request.
4. In the Expansion Phase: patients should be willing to undergo tumor core biopsy procedure at pre-treatment and on Day 4, Cycle 1 if, in the judgment of the investigator, it is considered clinically safe and appropriate to do so. This requirement is optional but preferred for patients in Dose Escalation.
5. Has adequate organ function.

Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days prior to starting the study drug. Both males and females and must agree to use effective birth control during the study if conception is possible during this interval.

Exclusion:

1. Has received prior treatment with TAS-119.
2. Has received treatment with any proscribed treatments within specified time frames prior to study drug administration.
3. Has a serious illness or medical condition(s).

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: Up to 2.5 Years
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals - Seidman Cancer Center
state: Ohio
city: Milano
country: Italy
facility: San Raffaele Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC Cancer Institute
city: Madrid
country: Spain
facility: START MADRID-FJD, Hospital Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: START Madrid Unidad de Ensayos Fase I
city: Sutton
country: United Kingdom
facility: The Institute of Cancer Research
state: Surrey
Study officials:
References:
citation: Mountzios G, Terpos E, Dimopoulos MA. Aurora kinases as targets for cancer therapy. Cancer Treat Rev. 2008 Apr;34(2):175-82. doi: 10.1016/j.ctrv.2007.09.005. Epub 2007 Nov 19.
citation: Ogawa E, Takenaka K, Katakura H, Adachi M, Otake Y, Toda Y, Kotani H, Manabe T, Wada H, Tanaka F. Perimembrane Aurora-A expression is a significant prognostic factor in correlation with proliferative activity in non-small-cell lung cancer (NSCLC). Ann Surg Oncol. 2008 Feb;15(2):547-54. doi: 10.1245/s10434-007-9653-8. Epub 2007 Nov 28.
citation: Xu HT, Ma L, Qi FJ, Liu Y, Yu JH, Dai SD, Zhu JJ, Wang EH. Expression of serine threonine kinase 15 is associated with poor differentiation in lung squamous cell carcinoma and adenocarcinoma. Pathol Int. 2006 Jul;56(7):375-80. doi: 10.1111/j.1440-1827.2006.01974.x.
citation: Nadler Y, Camp RL, Schwartz C, Rimm DL, Kluger HM, Kluger Y. Expression of Aurora A (but not Aurora B) is predictive of survival in breast cancer. Clin Cancer Res. 2008 Jul 15;14(14):4455-62. doi: 10.1158/1078-0432.CCR-07-5268.
citation: Lassmann S, Shen Y, Jutting U, Wiehle P, Walch A, Gitsch G, Hasenburg A, Werner M. Predictive value of Aurora-A/STK15 expression for late stage epithelial ovarian cancer patients treated by adjuvant chemotherapy. Clin Cancer Res. 2007 Jul 15;13(14):4083-91. doi: 10.1158/1078-0432.CCR-06-2775.
citation: Lagarde P, Perot G, Kauffmann A, Brulard C, Dapremont V, Hostein I, Neuville A, Wozniak A, Sciot R, Schoffski P, Aurias A, Coindre JM, Debiec-Rychter M, Chibon F. Mitotic checkpoints and chromosome instability are strong predictors of clinical outcome in gastrointestinal stromal tumors. Clin Cancer Res. 2012 Feb 1;18(3):826-38. doi: 10.1158/1078-0432.CCR-11-1610. Epub 2011 Dec 13.
citation: Reiter R, Gais P, Jutting U, Steuer-Vogt MK, Pickhard A, Bink K, Rauser S, Lassmann S, Hofler H, Werner M, Walch A. Aurora kinase A messenger RNA overexpression is correlated with tumor progression and shortened survival in head and neck squamous cell carcinoma. Clin Cancer Res. 2006 Sep 1;12(17):5136-41. doi: 10.1158/1078-0432.CCR-05-1650.
citation: Anand S, Penrhyn-Lowe S, Venkitaraman AR. AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell. 2003 Jan;3(1):51-62. doi: 10.1016/s1535-6108(02)00235-0.
citation: McGrogan BT, Gilmartin B, Carney DN, McCann A. Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008 Apr;1785(2):96-132. doi: 10.1016/j.bbcan.2007.10.004. Epub 2007 Nov 12.
citation: Beltran H, Rickman DS, Park K, Chae SS, Sboner A, MacDonald TY, Wang Y, Sheikh KL, Terry S, Tagawa ST, Dhir R, Nelson JB, de la Taille A, Allory Y, Gerstein MB, Perner S, Pienta KJ, Chinnaiyan AM, Wang Y, Collins CC, Gleave ME, Demichelis F, Nanus DM, Rubin MA. Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov. 2011 Nov;1(6):487-95. doi: 10.1158/2159-8290.CD-11-0130.
citation: Tajiri T, Tanaka S, Shono K, Kinoshita Y, Fujii Y, Suita S, Ihara K, Hara T. Quick quantitative analysis of gene dosages associated with prognosis in neuroblastoma. Cancer Lett. 2001 May 10;166(1):89-94. doi: 10.1016/s0304-3835(01)00434-7.
citation: Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff AC. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006 Jul 1;24(19):3187-205. doi: 10.1200/JCO.2006.06.4451. Epub 2006 May 8.
citation: Brockmann M, Poon E, Berry T, Carstensen A, Deubzer HE, Rycak L, Jamin Y, Thway K, Robinson SP, Roels F, Witt O, Fischer M, Chesler L, Eilers M. Small molecule inhibitors of aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma. Cancer Cell. 2013 Jul 8;24(1):75-89. doi: 10.1016/j.ccr.2013.05.005. Epub 2013 Jun 20.
citation: Kalliokoski A, Niemi M. Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705. doi: 10.1111/j.1476-5381.2009.00430.x. Epub 2009 Sep 25.
citation: Niemi M, Pasanen MK, Neuvonen PJ. Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81. doi: 10.1124/pr.110.002857. Epub 2011 Jan 18.
citation: Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
citation: Bogaerts J, Ford R, Sargent D, Schwartz LH, Rubinstein L, Lacombe D, Eisenhauer E, Verweij J, Therasse P; RECIST Working Party. Individual patient data analysis to assess modifications to the RECIST criteria. Eur J Cancer. 2009 Jan;45(2):248-60. doi: 10.1016/j.ejca.2008.10.027. Epub 2008 Dec 16.
citation: Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
citation: Raphael C, Briscoe C, Davies J, Ian Whinnett Z, Manisty C, Sutton R, Mayet J, Francis DP. Limitations of the New York Heart Association functional classification system and self-reported walking distances in chronic heart failure. Heart. 2007 Apr;93(4):476-82. doi: 10.1136/hrt.2006.089656. Epub 2006 Sep 27.
citation: Robbrecht DGJ, Lopez J, Calvo E, He X, Hiroshi H, Soni N, Cook N, Dowlati A, Fasolo A, Moreno V, Eskens FALM, de Bono JS. A first-in-human phase 1 and pharmacological study of TAS-119, a novel selective Aurora A kinase inhibitor in patients with advanced solid tumours. Br J Cancer. 2021 Jan;124(2):391-398. doi: 10.1038/s41416-020-01100-3. Epub 2020 Oct 6.