Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies.
Br J Cancer
; 116(12): 1505-1512, 2017 Jun 06.
Article
in En
| MEDLINE
| ID: mdl-28463960
ABSTRACT
BACKGROUND:
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).METHODS:
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.RESULTS:
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).CONCLUSIONS:
Roniciclib demonstrated an acceptable safety profile and moderate DCR in 3 days on/4 days off schedule.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrimidines
/
Sulfoxides
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Signal Transduction
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Neoplasms
/
Antineoplastic Agents
Type of study:
Clinical_trials
Limits:
Adult
/
Aged
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Aged80
/
Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Br J Cancer
Year:
2017
Document type:
Article
Affiliation country:
France