Oral administration of S 78454 in combination with cisplatin in patients with advanced non-keratinising nasopharyngeal carcinoma

ISRCTN	ISRCTN96922360
DOI	https://doi.org/10.1186/ISRCTN96922360
Secondary identifying numbers	CL1-78454-009

Submission date: 19/04/2012
Registration date: 08/06/2012
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

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

Contact information

Dr Boon Cher Goh
Scientific

National University Cancer Institute
Department of Haematology - Oncology
5 Lower Kent Ridge Road
Main Building 1, Level 3
-
119074
Singapore

Study information

Study design	Multicentre international non-randomised non-comparative open-label phase I study
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Screening
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	Phase I dose escalation study of oral administration of Pan-Histone Deacetylase (HDAC) inhibitor S 78454 given in combination with a fixed dose infusion of cisplatin in patients with advanced non-keratinising nasopharyngeal carcinoma.
Study hypothesis	Establish the safety and tolerability of S 78454 given in combination with a fixed dose infusion of cisplatin in patients with advanced non-keratinising nasopharyngeal carcinoma in terms of the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs), and establish the recommended Phase II dose (RP2D).
Ethics approval(s)	Ethics approval was obtained before recruitment of the first participants
Condition	Advanced non-keratinising nasopharyngeal carcinoma
Intervention	S 78454 capsules 80 mg twice a day (b.i.d.) to 140mg b.i.d. Cisplatin / 1 infusion per cycle / 75mg/m² maximum 1. At least 2 cycles of combination treatment. 2. Cisplatin limited to 6 cycles 3. S78454 as long as the disease does not progress and treatment sufficiently tolerated or consent withdrawal
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase I
Drug / device / biological / vaccine name(s)	Cisplatin
Primary outcome measure	1. MTD and DLTs of oral S 78454 capsules with a fixed dose infusion of cisplatin 2. Establish the recommended phase II dose
Secondary outcome measures	1. Safety profile (adverse events, laboratory tests, physical exam, ECOG, vital signs, ECG, clinical neurological examination, audiometric tests) 2. To determine pharmacokinetic (PK) profile 3. Measure Tumour response according to revised Response Evaluation Criteria In Solid Tumors (RECIST)_ and plasma Epstein-Barr Virus (EBV) DNA levels
Overall study start date	01/03/2012
Overall study end date	30/11/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	30 patients in the escalation part + 10 patients in the confirmatory part = 40 patients
Participant inclusion criteria	1. Male or female patients aged ≥21 (Singapore) ≥20 (Taiwan) 2. Histologically documented, measurable or evaluable advanced non-keratinising nasopharyngeal carcinoma, that has relapsed or is refractory to conventional, standard forms of therapy. 3. Ability to swallow oral capsule(s) without difficulty 4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 5. Estimated life expectancy > 12 weeks 6. Adequate haematological, renal and hepatic functions-Serum albumin 30 g/L 7. Written informed consent
Participant exclusion criteria	1. Pregnant or breastfeeding women, women of childbearing potential or men without effective contraception 2. Involvement in another clinical trial at the same time or within 4 weeks prior to inclusion, or patient already enrolled in the study 3. Major surgery within previous 4 weeks 4. Chemotherapy within previous 3 weeks (6 weeks in case of nitroso-ureas) 5. Biologic/target therapy or immunologic agents within previous 3 weeks 6. Radiotherapy within previous 4 weeks (except for palliative radiotherapy at localised lesions) 7. Abnormal thyroid function (defined as thyroid-stimulating hormone or free T4) except for patients with hypothyroidism diagnosed prior to study entry and stable on thyroid replacement 8. Concurrent therapeutic anticoagulation by anti-vitamin K (AVK) 9. Uncontrolled diabetes mellitus 10. Concomitant uncontrolled infection or severe systemic disease 11. Symptomatic or progressive brain metastasis 12. Patients with pre-existing gastrointestinal disorders 13. Patient with impaired cardiac function 14. Prior exposure to any Histone deacetylase inhibitors (HDACi) 15. Known organ dysfunction 16. Peripheral neuropathy > grade 1 17. Hearing impairment/tinnitus > grade 2 18. Known hypersensitivity to cisplatin
Recruitment start date	01/03/2012
Recruitment end date	30/11/2013

Locations

Countries of recruitment

Singapore
Taiwan

Study participating centre

National University Cancer Institute

-
119074
Singapore

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).