EXCITE: Erbitux, Xeloda, Campto, Irradiation Then Excision for locally advanced rectal cancer

ISRCTN	ISRCTN86285819
DOI	https://doi.org/10.1186/ISRCTN86285819
EudraCT/CTIS number	2007-006701-25
ClinicalTrials.gov number	NCT00972881
Secondary identifying numbers	4265

Submission date: 23/04/2010
Registration date: 23/04/2010
Last edited: 20/05/2019

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

Currently as of 08/03/2019:
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-cetuximab-capecitabine-and-irinotecan-with-radiotherapy-before-surgery-for-cancer-of-the-rectum

Previously:
https://www.cancerhelp.org.uk/trials/a-trial-looking-at-cetuximab-capecitabine-and-irinotecan-with-radiotherapy-before-surgery-for-cancer-of-the-rectum

Contact information

Miss Emma Williams
Scientific

Cancer Trials Office
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom

Study information

Study design	Randomised interventional treatment trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	EXCITE: Erbitux, Xeloda, Campto, Irradiation Then Excision for locally advanced rectal cancer (North West/North Wales Clinical Oncology Group-04 on behalf of the NCRI rectal cancer subgroup): a phase II trial from the North West/North Wales Clinical Oncology Group on behalf of the NCRI rectal cancer subgroup examining the toxicity and efficacy of Cetuximab, Capecitabine and Irinotecan in combination with radiotherapy as preoperative downstaging treatment for MRI-defined locally advanced rectal cancer
Study acronym	EXCITE
Study objectives	To assess the downstaging effectiveness and tolerability of preoperative chemoradiation therapy (CRT) using capecitabine/irinortecan/cetuximab plus radiotherapy. Treatment summary: Patients will be treated with pelvic radiotherapy to a planned volume at a dose of 45 Gy in 25 daily fractions of 1.8 Gy treating 5 days per week from Monday to Friday for five weeks in total. Concurrently they will receive oral capecitabine at 650 mg/m^2 twice daily (bd) for 5 days per week on the days of radiotherapy only. In addition, they will receive intravenous (IV) irinotecan at 60 mg/m^2 once per week during the 1st, 2nd, 3rd and 4th weeks of radiotherapy. In addition to this they will receive a loading dose of IV cetuximab at 400 mg/m^2 one week before the commencement of radiotherapy and then at 250 mg/m^2 once per week during the 1st, 2nd, 3rd 4th and 5th weeks of radiotherapy. On 20/10/2010 the following changes were made to this trial record: 1. The anticipated end date was changed from 30/03/2010 to 30/08/2011. 2. The phase was changed from phase I/II to phase II only. 3. The target number of participants was changed from 40 to 80.
Ethics approval(s)	Oxford Research Ethics Committee REC B, 15/01/2008, ref: 08/H0605/6
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: Colorectal Cancer; Disease: Rectum
Intervention	Patients will be treated with pelvic radiotherapy to a planned volume at a dose of 45 Gy in 25 daily fractions of 1.8 Gy treating 5 days per week from Monday to Friday for five weeks in total. Concurrently they will receive oral capecitabine at 650 mg/m^2 bd for 5 days per week on the days of radiotherapy only. In addition, they will receive IV irinotecan at 60 mg/m^2 once per week during the 1st, 2nd, 3rd and 4th weeks of radiotherapy. In addition to this they will receive a loading dose of IV cetuximab at 400 mg/m^2 one week before the commencement of radiotherapy and then at 250 mg/m^2 once per week during the 1st, 2nd, 3rd 4th and 5th weeks of radiotherapy. Follow-up length: 36 months Study entry: registration only
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Capecitabine, irinortecan, cetuximab
Primary outcome measure	Histologically confirmed R0 resection rate, measured at surgery when the tumour is resected (captured on Surgery CRF)
Secondary outcome measures	1. Radiotherapy compliance, measured during treatment weeks 2. Grade 3 or 4 toxicity, measured from treatment week 1 until end of follow-up month 36 3. Pathological complete response, measured at surgery when tumour is resected and examined 4. Morbidity, measured from surgery until end of follow-up month 36 5. Disease-free survival and local failure-free survival, measured from end of treatment until end of follow-up month 36
Overall study start date	30/03/2009
Completion date	30/08/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target number of participants	Planned sample size: 80; UK sample size: 80
Total final enrolment	82
Key inclusion criteria	Amended as of 20/10/2010: 1. Rectal cancer staged with magnetic resonance imaging (MRI) as locally advanced: 1.1. Mesorectal fascia threatened (tumour less than or equal to 1 mm from mesorectal fascia) 1.2. Mesorectal fascia involved or breached 1.3. Low tumours arising less than 5 cm from the anal verge 2. Histologically confirmed adenocarcinoma with lower (distal) limit less than or equal to 12 cm from the anal verge using rigid sigmoidoscopy 3. No evidence of metastatic disease 4. No pre-existing condition which would deter radiotherapy, e.g. fistulas, severe ulcerative colitis, Crohn's disease, prior adhesions 5. Estimated glomerular filtration rate (GFR) greater than 50 ml/min. If this is less than 50 ml/min a 24-hour urine collection for estimation of GFR is required or a serum EDTA clearance. 6. Absolute neutrophil count greater than or equal to 1.5 x 10^9/l 7. Platelets greater than or equal to 100 x 10^9/l, serum bilirubin less than 1.25 x upper limit of normal (ULN), serum transaminase less than 3 x ULN, serum ALP less than 5 x ULN 8. Fit to receive all study treatments 9. Able to comply with oral medication 10. Easter Cooperative Oncology Group (ECOG) performance status 0 or 1 11. Informed consent 12. Male and female, aged over 18 years Initial information at time of registration: 1. Magentic resonance imaging (MRI) defined locally advanced rectal cancer: 1.1. Mesorectal fascia involved, or 1.2. Mesorectal fascia threatened (tumour <1 mm from mesorectal fascia), or 1.3. Any T3 tumours less than 5 cm from anal verge 2. Histologically confirmed adenocarcinoma 3. No evidence of metastatic disease 4. No pre-existing condition which would deter radiotherapy, e.g. fistulas, severe ulcerative colitis, Crohn's disease, prior adhesions 5. Estimated glomerular filtration rate (GFR) greater than 50 ml/min. If this is less than 50 ml/min a 24-hour urine collection for estimation of GFR is required or a serum EDTA clearance. 6. Absolute neutrophil count greater than or equal to 1.5 x 10^9/l 7. Platelets greater than or equal to 100 x 10^9/l, serum bilirubin less than 1.25 x upper limit of normal (ULN), serum transaminase less than 3 x ULN, serum ALP less than 5 x ULN 8. Fit to receive all study treatments 9. Able to comply with oral medication 10. Easter Cooperative Oncology Group (ECOG) performance status 0 or 1 11. Informed consent 12. Male and female, aged over 18 years
Key exclusion criteria	1. Previous chemotherapy 2. Previous radiotherapy to the pelvis 3. Patients who have very significant small bowel delineated within the radiation fields 4. Current or impending rectal obstruction, metallic colonic stent in situ 5. Pelvic sepsis 6. Uncontrolled cardiac, respiratory or other disease, or any serious medical or psychiatric disorder that would preclude trial therapy or informed consent 7. Known dihydropyrimidine dehydrogenase deficiency 8. Pregnant, lactating or women of childbearing potential not using adequate contraception 9. World Health Organization (WHO) performance greater than 2 10. Gastrointestinal disorder which would interfere with oral therapy or oral bioavailability 11. Patients unsuitable for surgery because of co-morbidity or coagulation problems 12. Participation in other studies except genetic studies such as NSCCG
Date of first enrolment	30/03/2009
Date of final enrolment	30/08/2011

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Cancer Trials Office

London
W1T 4TJ
United Kingdom

Sponsor information

University College London (UK)
Government

Gower Street
London
WC1E 6BT
United Kingdom

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

Funders

Funder type

Charity

Cancer Research UK (CRUK) (UK)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

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	Peer reviewed?	Patient-facing?
Basic results			No	No
Protocol file		07/05/2010	No	No
Abstract results	conference abstract	20/01/2014	No	No
Abstract results	conference abstract	01/09/2015	No	No
Abstract results	conference abstract	01/11/2017	No	No

Additional files

ISRCTN86285819_PROTOCOL_07MAY2010.pdf

Editorial Notes

20/05/2019: The total final enrolment was added.
08/03/2019: The following changes were made to the trial record:
1. Publication references added
2. Uploaded protocol version 4.0 07 May 2010 (not peer reviewed)
3. The plain English summary link was updated
4. Basic results (scientific) were added.
13/04/2017: No publications found in PubMed, verifying study status with principal investigator.