Erbitux in preoperative chemo-radiotherapy followed by excisional surgery

ISRCTN	ISRCTN11319909
DOI	https://doi.org/10.1186/ISRCTN11319909
EudraCT/CTIS number	2004-001926-26
Secondary identifying numbers	1680

Submission date: 12/05/2010
Registration date: 12/05/2010
Last edited: 29/07/2024

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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-giving-biological-therapy-as-well-as-combined-chemotherapy-and-radiotherapy-before-surgery-cancer-back-passage-xerxes

Contact information

Dr Wendy Wood
Scientific

CR UK and UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom

Study information

Study design	Multicentre non-randomized interventional treatment trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Examining the role of Early Neoadjuvant and Synchronous Erbitux in Preoperative Chemo-Radiotherapy using Xeloda followed by Excisional Surgery
Study acronym	XERXES
Study objectives	This is a multicentre pilot trial to establish the role of intravenous cetuximab when added to a schedule of capecitabine plus pelvic radiation in patients who have locally advanced primary rectal cancers. Cetuximab will be given by intravenous (iv) infusion at a loading dose of 400 mg/m^2 and subsequently at 250 mg/m^2 weekly. Capecitabine will be taken twice daily (bd) by mouth at 825 mg/m^2 bd on Monday - Friday each week for 5 weeks during radiotherapy. Toxicity during treatment will be evaluated and the frequency of toxicity-led dose reductions and delays will be monitored closely. The aim is to determine the toxicity for this combined modality schedule, and a preliminary assessment of efficacy for future evaluation in a randomised controlled trial. Whilst efficacy data are always limited in a small feasibility study, radiological +/- histopathological assessment in the surgical specimen will be used to provide preliminary measures of efficacy in this patient cohort. This study offers the opportunity to obtain biopsy material on chemo-naïve patients with rectal cancer and to examine the histological and downstream effects of single agent cetuximab.
Ethics approval(s)	Fife and Forth Valley Research Ethics Committee, 06/04/2005, ref: 05/S0501/49
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: Colorectal Cancer; Disease: Rectum
Intervention	All patients receive the following: Radiotherapy: planned total dose of 45 Gy in 25 fractions using a three or four field plan in 33 days. Capecitabine: 825 mg/m^2 twice daily orally (Mon - Fri) over 5 weeks during radiotherapy. Radical Surgery: to be undertaken ideally 6 - 10 weeks following completion of chemoradiation. Group 1: the first 12 patients will receive cetuximab 400 mg/m2 in a short iv infusion as a starting dose then a weekly dose of 250 mg/m2 for 4 weeks prior to chemoradiation (days 3, 10, 17, 24). Group 2: the subsequent 48 patients will be randomised into: Arm A: Chemoradiotherapy only (no cetuximab) Arm B: Cetuximab at the above doses for 4 weeks prior to chemoradiation and 5 weeks after (not during) Study entry: registration only
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Cetuximab, capecitabine
Primary outcome measure	1. Acute Toxicity (Grade 3 or above in defined DLT) 2. Compliance with the planned dose of radiotherapy Assessed after the patient has had surgery.
Secondary outcome measures	1. Histopathological downstaging (yPT0,T1,T2 N0) 2. Histologically confirmed (R0) resection Assessed after the patient has had surgery.
Overall study start date	06/12/2005
Completion date	01/04/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned sample size: 60
Total final enrolment	22
Key inclusion criteria	1. Adenocarcinoma of the rectum (within 15 cm of anal verge) 2. Tumour tissue available for testing of epidermal growth factor receptor (EGFR) status 3. Indication for pre-operative chemoradiotherapy with R0 resection unlikely 4. Fit for chemotherapy 5. Written informed consent for both treatment and biopsies 6. Male and female, lower age limit of 18 years
Key exclusion criteria	1. Previous radiotherapy to the pelvis 2. Previous pelvic resectional surgery (cystectomy, hysterectomy) 3. Previous chemotherapy or radiation for rectal cancer 4. Previous chemotherapy for metastatic disease 5. Patients who have very significant small bowel delineated within the radiation fields 6. Currently enrolled in any other treatment trial
Date of first enrolment	06/12/2005
Date of final enrolment	01/04/2014

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

CR UK and UCL Cancer Trials Centre

London
W1T 4TJ
United Kingdom

Sponsor information

University College London (UK)
University/education

Gower Street
London
WC1E 6BT
England
United Kingdom

Website	http://www.ucl.ac.uk
"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Industry

Merck Sharp & Dohme Ltd (MSD) (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results			16/05/2019	No	No
Plain English results			29/07/2024	No	Yes

Editorial Notes

29/07/2024: Cancer Research UK plain English results and total final enrolment added.
16/05/2019: Added clinicaltrialsregister.eu link to basic results (scientific).
07/12/2016: No publications found in PubMed, verifying study status with principal investigator.
01/10/2012: Recruitment for this study is closed.
05/10/2012: The anticipated end date of the trial was updated from 01/06/2011 to 01/04/2014