Additional identifiers
EudraCT/CTIS number
IRAS number
ClinicalTrials.gov number
Protocol/serial number
CL1-78454-009
Study information
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.
Acronym
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
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
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
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
Reason abandoned (if study stopped)
Eligibility
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 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 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
Organisation
Institut de Recherches Internationales Servier (France)
Sponsor details
50 rue Carnot
Suresnes
92284
France
Sponsor type
Industry
Website
ROR
Funders
Funder type
Industry
Funder name
Institut de Recherches Internationales Servier (France)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Publication plan:
Summary results are published in https://clinicaltrials.servier.com.
Intention to publish date
Individual participant data (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.
IPD sharing plan summary
Available on request
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | No | No |