Phase I study of S 78454 with tamoxifen 20 mg in patients with breast cancer

ISRCTN	ISRCTN25889030
DOI	https://doi.org/10.1186/ISRCTN25889030
Protocol serial number	CL1-78454-011
Sponsor	Pharmacyclics LLC (USA)
Funder	Pharmacyclics LLC (USA)

Submission date: 03/04/2014
Registration date: 29/04/2014
Last edited: 29/05/2020

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

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

Contact information

Dr Suzette Delaloge
Scientific

Institut Gustave Roussy
114 rue Edouard Vaillant
Villejuif
94805
France

Study information

Primary study design	Interventional
Study design	International multicentric non-randomised open dose-escalation Phase I study.
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	Phase I dose-escalation study of oral administration of S 78454 given with tamoxifen 20 mg in the treatment of patients with advanced breast cancer
Study objectives	To establish the safety profile and the recommended Phase II dose of S 78454 in combination with a fixed dose of tamoxifen 20 mg.
Ethics approval(s)	Ethics approval was obtained before recruitment of the first participants
Health condition(s) or problem(s) studied	Advanced breast cancer
Intervention	Capsules containing 20 mg and 100 mg of S 78454 / oral use / 120 mg b.i.d to 160 mg b.i.d (dose de-escalation up to 80 mg b.i.d can be performed), and Fixed dose of tamoxifen 20 mg per day / oral use Treatment duration is at the discretion of the investigator
Intervention type	Drug
Phase	Phase I
Drug / device / biological / vaccine name(s)	S 78454, tamoxifen
Primary outcome measure(s)	1. Dose limiting toxicities and maximum tolerated doses at the end of cycle 2. Methods used: blood samples, physical examination, vital signs assessment, ECG 2. Safety profile of the combination at each visit (adverse events, laboratory tests, physical examination, ECOG, vital signs, ECG)
Key secondary outcome measure(s)	1. Pharmacokinetic evaluation within cycle 2 by blood samples 2. Pharmacodynamic assessment every cycle by blood samples 3. Tumour response evaluation every two cycles according to RECIST criteria
Completion date	28/01/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target sample size at registration	40
Key inclusion criteria	1. Female patients aged 18 years or over 2. Ability to swallow oral capsule(s) 3. Estimated life expectancy > 12 weeks 4. ECOG performance status less than or equal to 1 5. Adequate haematological and hepatic functions 6. Histologically confirmed primary adenocarcinoma of the breast 7. Patients whose tumor has significant expression of Estrogen Receptor 8. Absence of Human Epidermal Growth Factor Receptor-2 overexpression or amplification
Key exclusion criteria	1. Major surgery within previous 4 weeks 2. Any previous chemotherapy within 3 weeks (6 weeks in case of nitroso-ureas) before starting the study drug 3. Any radiotherapy within previous 4 weeks (except for palliative radiotherapy at localised lesions) 4. Any other prior therapy directed at breast cancer within previous 3 weeks, including biologic/targeted therapy or immunologic agents 5. Hormonotherapy within 2 weeks, except stable oral glucocorticoid and mineralocorticoid replacement for adrenal insufficiency, topical corticosteroids (e.g. cream, spray) 6. Concomitant uncontrolled infection or systemic disease 7. Known endometrial hyperplasia, or endometrial cancer 8. Patients with prior thromboembolic events or at high risk of such events 9. Rapidly progressive visceral, central nervous system, or liver metastases or significant symptomatic lymphangitic pulmonary metastases 10. Patients with pre-existing gastrointestinal disorders (including significant malabsorption syndrome, significant chronic digestive or gastrointestinal inflammatory syndrome, gastroduodenal disorders at risk for bleeding) that might interfere with proper absorption of the oral drugs 11. Patients with impaired cardiac function
Date of first enrolment	30/08/2012
Date of final enrolment	07/07/2014

Locations

Countries of recruitment

France
Italy
Spain

Study participating centre

Institut Gustave Roussy

Villejuif
94805
France

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

29/05/2020: No publications found.
17/12/2015: The following changes were made to the trial record:
1. Sponsoring/funding responsibility for the S 78454 project was transferred from Servier, France to Pharmacyclics, USA on 23/11/2014.
2. The overall trial end date was changed from 31/12/2015 to 28/01/2015.