Title |
Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies
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Published in |
British Journal of Cancer, May 2017
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DOI | 10.1038/bjc.2017.92 |
Pubmed ID | |
Authors |
Rastislav Bahleda, Juneko E Grilley-Olson, Ramaswamy Govindan, Fabrice Barlesi, Laurent Greillier, Maurice Perol, Isabelle Ray-Coquard, Dirk Strumberg, Beate Schultheis, Grace K Dy, Gérard Zalcman, Glen J Weiss, Annette O Walter, Martin Kornacker, Prabhu Rajagopalan, David Henderson, Hendrik Nogai, Matthias Ocker, Jean-Charles Soria |
Abstract |
To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway. Ten patients were evaluable in the 4 weeks on/2 weeks off schedule (terminated following limited tolerability) and 47 in the 3 days on/4 days off schedule dose-escalation cohorts. On the 3 days on/4 days off schedule, RP2D was 5 mg twice daily in solid tumours (n=40); undetermined in lymphoid malignancies (n=7). Common roniciclib-related adverse events included nausea (76.6%), fatigue (65.8%), diarrhoea (63.1%), and vomiting (57.7%). Roniciclib demonstrated rapid absorption and dose-proportional increase in exposure. One partial response (1.0%) was observed. In RP2D expansion cohorts, the disease control rate (DCR) was 40.9% for patients with ovarian cancer (n=25), 17.4% for patients with SCLC (n=33), and 33.3% for patients with CDK-related tumour mutations (n=6). Roniciclib demonstrated an acceptable safety profile and moderate DCR in 3 days on/4 days off schedule.British Journal of Cancer advance online publication, 2 May 2017; doi:10.1038/bjc.2017.92 www.bjcancer.com. |
X Demographics
Geographical breakdown
Country | Count | As % |
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France | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 45 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 10 | 22% |
Student > Ph. D. Student | 5 | 11% |
Student > Master | 4 | 9% |
Researcher | 4 | 9% |
Other | 3 | 7% |
Other | 5 | 11% |
Unknown | 14 | 31% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 13 | 29% |
Biochemistry, Genetics and Molecular Biology | 4 | 9% |
Nursing and Health Professions | 3 | 7% |
Agricultural and Biological Sciences | 2 | 4% |
Business, Management and Accounting | 1 | 2% |
Other | 5 | 11% |
Unknown | 17 | 38% |