Phase I study of S 78454 in combination with a fixed dose infusion of cisplatin in patients with advanced solid tumours

ISRCTN	ISRCTN85966108
DOI	https://doi.org/10.1186/ISRCTN85966108
Secondary identifying numbers	CL1-78454-008

Submission date: 04/10/2013
Registration date: 09/12/2013
Last edited: 18/04/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration and not expected to be available in the future

Contact information

Dr Anthony Goncalves
Scientific

Institut Paoli Calmettes
Oncologie Médicale
232 Boulevard Sainte Marguerite
Marseille Cedex 9
13273
France

Study information

Study design	National multicentric non-randomised open-label dose escalation Phase I study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Phase I dose-escalation study of oral administration of the Histone Deacetylase (HDAC) Inhibitor S 78454 given in combination with a fixed dose infusion of Cisplatin in patients with advanced solid tumours
Study objectives	To establish the safety profile and the recommended Phase II dose of S 78454 in combination with a fixed dose infusion of cisplatin
Ethics approval(s)	Ethic approval was obtained before recruitment of the first participants
Health condition(s) or problem(s) studied	Advanced solid tumours
Intervention	1. Capsules containing 20 mg and 100 mg of S 78454 / Oral use / Treatment duration is at the discretion of the investigator 2. Fixed dose of i.v. infusion of cisplatin at 75 mg/m² / Cisplatin administration for up to 6 cycles, S 78454 could be maintained beyond
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase I
Drug / device / biological / vaccine name(s)	S 78454, cisplatin
Primary outcome measure	1. DLTs and MTDs within the cycle 1 - Methods used: blood samples (biochemistry, haematology, coagulation analysis), physical examination and vital signs assessment, urinary analysis, ECG, clinical neurological examination, audiometric test 2. Safety profile of the combination at each visit
Secondary outcome measures	1. Pharmacokinetic evaluation on cycle 1 by blood sample 2. Circulating Tumour Cells measurements every 2 cycles by blood sample 3. Tumour response evaluation every 2 cycles according to RECIST criteria
Overall study start date	05/04/2012
Completion date	05/02/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Up to 50 patients
Key inclusion criteria	1. Male or female patient aged > or equal to 18 years 2. Any histological confirmed diagnosis of advanced solid tumours that have relapsed or is refractory to conventional standard forms of therapy 3. Ability to swallow oral capsule(s) 4. Estimated life expectancy > 12 weeks 5. ECOG performance status < or equal to 1 6. Adequate haematological, renal and hepatic functions
Key exclusion criteria	1. Major surgery within previous 4 weeks 2. Chemotherapy within previous 3 weeks (6 weeks for nitroso-ureas) 3. Hormonotherapy within 2 weeks (6 weeks for bicalutamide) 4. Any other prior therapy directed at the solid tumours within 3 weeks 5. Radiotherapy within previous 4 weeks (except for palliative radiotherapy at localised lesions) 6. Cumulative radiation therapy involving > 25 % of total bone marrow 7. Pregnant or breast-feeding women, women of childbearing potential or men without effective contraception 8. Peripheral Neuropathy > grade 1 9. Hearing impairment/tinnitus > grade 2 10. Prior treatment with cisplatin reaching a cumulative dose of 300 mg/m² 11. Concomitant uncontrolled infection or severe systemic disease 12. Symptomatic or progressive brain metastasis 13. Patients with pre-existing gastrointestinal disorders 14. Concurrent therapeutic anticoagulation by AVK 15. Patient with impaired cardiac function 16. Patients with pre-existing gastro-intestinal disorders 17. Uncontrolled diabetes mellitus
Date of first enrolment	05/04/2012
Date of final enrolment	05/02/2014

Locations

Countries of recruitment

France

Study participating centre

Institut Paoli Calmettes

Marseille Cedex 9
13273
France

Sponsor information

Institut de Recherches Internationales Servier (France)
Industry

50 rue Carnot
Suresnes
92284
France

Website	http://www.servier.com/
"ROR"	https://ror.org/034e7c066

Funders

Funder type

Industry

Institut de Recherches Internationales Servier (France)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Publication plan: Summary results are published in https://clinicaltrials.servier.com.
IPD sharing plan	The datasets generated during and/or analysed during the current study will be available upon request from https://clinicaltrials.servier.com if a Marketing Authorisation has been granted after 1st January 2014.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results				No	No

Editorial Notes

18/04/2018: Internal review.
28/03/2018: Publication and dissemination plan and IPD sharing statement updated.
24/01/2018: Publication plan and IPD sharing statement added.
29/11/2017: Results summary added.
17/12/2015: Sponsoring/funding responsibility for the S 78454 project was transferred from Servier, France to Pharmacyclics, USA on 23/11/2014. However, as this study has already been completed at this time, the sponsor/funder remains stated as Servier. However, in case of any questions, please contact Pharmacyclics (info@pcyc.com).