Condition category
Cancer
Date applied
28/11/2008
Date assigned
17/12/2008
Last edited
14/04/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Maria Michelagnoli

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

08/0230

Study information

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

Acronym

OTIS

Study hypothesis

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

Derby 1 (Trent) and Derby 2 Research Ethics Committees, 07/08/2009, ref: 09H0405-29

Study design

Non-randomised phase II study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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 names

Treosulfan

Primary outcome measures

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.

Secondary outcome measures

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

Overall trial start date

01/03/2009

Overall trial end date

11/09/2012

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Other

Gender

Both

Target number of participants

25 patients in total

Participant 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

Recruitment start date

02/02/2010

Recruitment end date

11/09/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University College London
London
NW1 2PG
United Kingdom

Sponsor information

Organisation

University College London (UK)

Sponsor details

c/o Joanna Galea-Lauri
Head of Clinical Trials
Joint UCLH and UCL Biomedical Research Unit
Ground Floor
Rosenheim Wing
25 Grafton Way
London
WC1E 5DB
United Kingdom

Sponsor type

University/education

Website

http://www.ucl.ac.uk/

Funders

Funder type

Charity

Funder name

Adam Dealey Foundation (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Medac International (UK)

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

2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25284019

Publication citations

Additional files

Editorial Notes