Condition category
Cancer
Date applied
19/04/2012
Date assigned
08/06/2012
Last edited
17/12/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Dr Boon Cher Goh

ORCID ID

Contact details

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

Additional identifiers

EudraCT 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

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 controlled trial

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Not available in web format, please use the contact details below 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

Phase

Phase I

Drug names

Cisplatin

Primary outcome measures

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 trial start date

01/03/2012

Overall trial end date

30/11/2013

Reason abandoned

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

Patient

Age group

Adult

Gender

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 breast-feeding women, women of child-bearing 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

Trial 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

http://www.servier.com/

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

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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).