Condition category
Cancer
Date applied
09/09/2005
Date assigned
03/10/2006
Last edited
26/06/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof David Cunningham

ORCID ID

Contact details

Royal Marsden Hospital
Downs Road
Sutton
Surrey
SM2 5PT
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MREC 05/Q1604/16

Study information

Scientific title

Acronym

EXPERT-C

Study hypothesis

To evaluate the improvement in pathological complete response rate from the addition of cetuximab to neoadjuvant oxaliplatin and capecitabine followed by synchronous chemoradiation and Total Mesorectal Excision (TME) in patients with Magnetic Resonance Imaging (MRI) defined high risk rectal cancer.

Ethics approval

Oxfordshire Research Ethics Committee A, approval was given on 05/04/2005

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

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

Condition

Rectal cancer

Intervention

Group one: receiving oxaliplatin (Eloxatin), capecitabine (Xeloda) and pre-operative radiotherapy with cetuximab followed by TME.
Group two: receiving oxaliplatin (Eloxatin), capecitabine (Xeloda) and pre-operative radiotherapy without cetuximab followed by TME.

Intervention type

Drug

Phase

Phase II

Drug names

Oxaliplatin, capecitabine, cetuximab.

Primary outcome measures

Pathological complete response at TME.

Secondary outcome measures

1. Radiological response rates after neoadjuvant chemotherapy and after completion of all neoadjuvant chemoradiotherapy
2. Complete resection rate (R0 resection) with microscopic clear resection margin (tumour observed more than 1 mm from the resection margin), especially circumferential resection margin
3. Perioperative measures including operation time, duration of in-patient stay, peri-operative transfusion requirement and mortality within 30 days of operation
4. Post-operative complications including wound infection, wound dehiscence fistula formation
5. Quality of TME as graded by audit of photographed surgical specimens
6. Rate of Abdomino-Peritoneal Excision (APE)
7. Rate of permanent defunctioning colostomies
8. Clinical and radiological anastomotic leak rate
9. Progression free survival and patterns of failure
10. Overall survival
11. Safety
13. Quality of life including long term bowel function
13. Evaluation of molecular and genetic predictors of response to anti-Epidermal Growth Factor Receptor (anti-EGFR) treatment
14. Evaluation of gene expression changes which occur in response to treatment with cetuximab, and to correlate these changes with response to treatment and prognosis.

Overall trial start date

01/09/2005

Overall trial end date

01/09/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 18 years or over
2. Histological diagnosis of adeno- or undifferentiated non-small cell carcinoma of rectum
3. High risk operable rectal cancer as defined by the presence on MRI of at least one of the following:
a. tumours within 1 mm of mesorectal fascia i.e. circumferential resection margin threatened or involved
b. T3 tumours at/below levators
c. tumours extending into more than or equal to 5 mm into peri-rectal fat
d. T4 tumours (including the involvement of bladder or vagina if surgical resection is possible with clear margins)
e. presence of extra-mural venous invasion (primary tumour is therefore at least T3)
4. World Health Organisation (WHO) performance status of zero to two
5. No evidence of metastatic disease as determined by Computerised Tomography (CT) scan of chest and abdomen or other investigations such as Positron Emission Tomography (PET) scan or biopsy if required
6. Adequate bone marrow function with platelets more than 100 x 10^9/l, White Blood Cells (WBC) more than 3 x 10^9/l and neutrophils more than 1.5 x 10^9/l
7. Serum bilirubin less than 1.5 x Upper Limit of institutional Normal range (ULN) and transaminases less than 2.5 x ULN
8. Serum creatinine less than ULN or calculated creatinine clearance more than 50 ml/min
9. No concurrent uncontrolled medical condition
10. No active malignant disease other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix in the last ten years
11. Life expectancy of more than three months
12. Adequate contraceptive precautions if relevant
13. Informed written consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

164

Participant exclusion criteria

1. Any contraindications to MRI (e.g. patients with pacemakers)
2. Medical or psychiatric conditions that compromise the patient’s ability to give informed consent
3. Patients with rectal cancer which is deemed inoperable at diagnosis should not be entered into the study even if they are potentially operable if their primary is successfully downstaged by neoadjuvant treatment. This includes patients with locally advanced inoperable disease, such as tumour extending beyond the mesorectal fascia into pelvic side wall structures, or situations where surgical resection with clear margins is unlikely to be possible
4. T1-2 rectal cancer at any level
5. Presence of metastatic disease or recurrent rectal tumour
6. Concurrent uncontrolled medical conditions
7. Any previous chemotherapy or radiotherapy, and any investigational treatment for rectal cancer
8. Pregnancy or breast feeding
9. Patients with known malabsorption syndromes or a lack of physical integrity of the upper gastrointestinal tract
10. Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac dysrhythmia, e.g. atrial fibrillation, even if controlled with medication) or myocardial infarction within the last 12 months
11. Patients with any symptoms or history of peripheral neuropathy

Recruitment start date

01/09/2005

Recruitment end date

01/09/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Marsden Hospital
Surrey
SM2 5PT
United Kingdom

Sponsor information

Organisation

Royal Marsden NHS Foundation Trust (UK)

Sponsor details

Downs Road
Sutton
Surrey
SM2 5PT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.royalmarsden.nhs.uk/rmh

Funders

Funder type

Industry

Funder name

Professor Cunningham's Clinical Research Fund, Merck Pharmaceuticals (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

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24146218
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24957073

Publication citations

  1. Results

    Sclafani F, Roy A, Cunningham D, Wotherspoon A, Peckitt C, Gonzalez de Castro D, Tabernero J, Glimelius B, Cervantes A, Eltahir Z, Oates J, Chau I, HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab., Ann. Oncol., 2013, 24, 12, 3123-3128, doi: 10.1093/annonc/mdt408.

  2. Results

    Sclafani F, Gonzalez D, Cunningham D, Hulkki Wilson S, Peckitt C, Tabernero J, Glimelius B, Cervantes A, Dewdney A, Wotherspoon A, Brown G, Tait D, Oates J, Chau I, TP53 mutational status and cetuximab benefit in rectal cancer: 5-year results of the EXPERT-C trial., J. Natl. Cancer Inst., 2014, 106, 7, doi: 10.1093/jnci/dju121.

Additional files

Editorial Notes