Condition category
Cancer
Date applied
12/05/2010
Date assigned
12/05/2010
Last edited
07/12/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Wendy Wood

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

2004-001926-26

ClinicalTrials.gov number

Protocol/serial number

1680

Study information

Scientific title

Examining the role of Early Neoadjuvant and Synchronous Erbitux in Preoperative Chemo-Radiotherapy using Xeloda followed by Excisional Surgery

Acronym

XERXES

Study hypothesis

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

Fife and Forth Valley Research Ethics Committee, 06/04/2005, ref: 05/S0501/49

Study design

Multicentre non-randomised interventional treatment trial

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

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

Phase

Phase II

Drug names

Cetuximab, capecitabine

Primary outcome measures

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 trial start date

06/12/2005

Overall trial end date

01/04/2014

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned sample size: 60

Participant 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

Recruitment start date

06/12/2005

Recruitment end date

01/04/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

CR UK and UCL Cancer Trials Centre
London
W1T 4TJ
United Kingdom

Sponsor information

Organisation

University College London (UK)

Sponsor details

Gower Street
London
WC1E 6BT
United Kingdom

Sponsor type

University/education

Website

http://www.ucl.ac.uk

Funders

Funder type

Industry

Funder name

Merck Sharp & Dohme Ltd (MSD) (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

Publication citations

Additional files

Editorial Notes

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