Oral Treosulfan In Ewing's Sarcoma

ISRCTN	ISRCTN11631773
DOI	https://doi.org/10.1186/ISRCTN11631773
Protocol serial number	08/0230
Sponsor	University College London (UK)
Funders	Adam Dealey Foundation (UK), Medac International (UK)

Submission date: 28/11/2008
Registration date: 17/12/2008
Last edited: 25/01/2022

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 of protocol

http://www.cancerhelp.org.uk/trials/a-trial-looking-treosulfan-treat-Ewings-sarcoma-come-back-after-treatment-OTIS

Contact information

Dr Maria Michelagnoli
Scientific

University College London
6th Floor Central
250 Euston Road
London
NW1 2PG
United Kingdom

Study information

Primary study design	Interventional
Study design	Non-randomised phase II study
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	A phase II study to determine the efficacy and safety of conventional dose oral treosulfan in patients with advanced pre-treated Ewing's sarcoma
Study acronym	OTIS
Study objectives	This is a non-randomised phase II study which aims to explore the efficacy and toxicity of oral treosulfan in patients with advanced, pre-treated Ewing's sarcoma. If conventional dose oral treosulfan is demonstrated to be active in patients with advanced Ewing's sarcoma, it is proposed that this study should be followed by a phase III prospective randomised controlled trial comparing oral etoposide (the traditional active palliation agent in solid tumours) with oral treosulfan.
Ethics approval(s)	Derby 1 (Trent) and Derby 2 Research Ethics Committees, 07/08/2009, ref: 09H0405-29
Health condition(s) or problem(s) studied	Ewing's sarcoma
Intervention	Non-randomised phase II study of oral treosulfan in advanced pre-treated Ewing's sarcoma. Treosulfan 1 g/m^2 will be administered in three divided doses, daily over 7 days and repeated every 28 days, until disease progression, unacceptable toxicity or patient refusal.
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Treosulfan
Primary outcome measure(s)	Current primary outcomes measure as of 29/11/2011: Objective response rate achieved: tumour response will be measured as defined by the RECIST guidelines. Previous primary outcome measure: Objective response rate achieved: tumour response will be measured as defined by the RECIST guidelines. Following analysis of data for initial 15 patients, if the measured success is less than or equal to 10% then the study will be stopped. Otherwise, the study will close once a total of 25 eligible patients have been enrolled.
Key secondary outcome measure(s)	Current secondary outcome measures as of 29/11/2011: 1. Event-free survival 2. Overall survival 3. Toxicity : if there is more than one toxic death, or more than two unexpected treatment related serious adverse events occurring in two separate individuals, an Independent Data Monitoring Committee meeting will take place and advice sought regarding continuing the trial 4. Duration of response 5. Time to progression/relapse Previous secondary outcome measures: 1. Toxicity: if there is more than one toxic death, or more than two unexpected serious adverse events occurring in two separate individuals, the chief/co-investigators will consider stopping the trial 2. Duration of response 3. Time to progression 4. Correlation of deoxyribonucleic acid (DNA) cross-linking and retention with response and toxicity
Completion date	11/09/2012

Eligibility

Participant type(s)	Patient
Age group	Other
Sex	All
Target sample size at registration	25
Total final enrolment	21
Key inclusion criteria	Current inclusion criteria as of 29/11/2011: 1. Age less than 50 years, either sex 2. Histologically proven Ewing's sarcoma/peripheral neuroectodermal tumour 3. Patients with advanced, refractory disease who have failed at least one course of conventional chemotherapy and for whom no curative option exists 4. Measurable disease, defined by Response Evaluation Criteria in Solid Tumors (RECIST) 5. Evidence of disease progression within the preceding 8 weeks 6. Neutrophils greater than or equal to 1.5 x 10^9/l and platelet count greater than or equal to 100 x 10^9/l 7. Creatinine less than or equal to 1.5 x upper limit of normal (ULN) 8. Serum bilirubin and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than or equal to 1.5 x ULN 9. Performance status 0-2 (patients 16 years or older) or Lansky Performance Status greater than 30 (patients under 16 years). (n.b. patients with WHO performance status 3 due to spinal disease will be eligible provided they are otherwise medically well) 10. Patient able to comply with protocol treatment (swallow capsules) and follow up 11. Life expectancy of three months or greater 12. Written informed consent of patient or parent/legal guardian Previous inclusion criteria: 9. World Health Organization (WHO) performance status greater than 3 (patients greater than 16 years); or Lansky Performance Status greater than 30
Key exclusion criteria	1. Newly diagnosed, or resectable Ewing's sarcoma 2. Pregnant/lactating women, or women of childbearing potential unless using effective contraception 3. Concurrent treatment with any other anti-cancer therapy, except palliative radiotherapy to non-target lesions 4. Concurrent treatment with other experimental drugs 5. Concurrent treatment with growth factors
Date of first enrolment	02/02/2010
Date of final enrolment	11/09/2012

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

University College London

London
NW1 2PG
United Kingdom

Results and Publications

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

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/01/2015		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results		28/05/2015	25/01/2022	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

25/01/2022: The following changes have been made:
1. The Cancer Research UK lay results summary has been added.
2. The total final enrolment number has been added.