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

• Register: ISRCTN
• Last refreshed on: 21 May 2018
• Main ID: ISRCTN85966108
• Date of registration: 09/12/2013
• Prospective Registration: No
• Primary sponsor: Institut de Recherches Internationales Servier (France)
• Public title: Phase I study of S 78454 in combination with a fixed dose infusion of cisplatin in patients with advanced solid tumours
• 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
• Date of first enrolment: 05/04/2012
• Target sample size: 50
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN85966108
• Study type: Interventional
• Study design: National multicentric non-randomised open-label dose escalation Phase I study (Treatment)
• Phase: Phase I

Countries of recruitment

France

Contacts

• Name: Anthony Goncalves

Key inclusion & exclusion criteria

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
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

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Advanced solid tumours
Cancer

Intervention(s)

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

Primary Outcome(s)

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(s)

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

Secondary ID(s)

CL1-78454-008

Source(s) of Monetary Support

Institut de Recherches Internationales Servier (France)

Ethics review

Status:
Approval date:
Contact:

Ethic approval was obtained before recruitment of the first participants

Results

• Results available: Yes
• Date Completed: 05/02/2014