A multicentre randomised phase II clinical trial comparing oxaliplatin (Eloxatin), capecitabine (Xeloda) and pre-operative radiotherapy with or without cetuximab followed by total mesorectal excision for the treatment of patients with magentic resonance imaging defined high risk rectal cancer
| ISRCTN | ISRCTN99828560 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN99828560 |
| Secondary identifying numbers | MREC 05/Q1604/16 |
- Submission date
- 09/09/2005
- Registration date
- 03/10/2006
- Last edited
- 26/06/2014
- 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
Not provided at time of registration
Contact information
Prof David Cunningham
Scientific
Scientific
Royal Marsden Hospital
Downs Road
Sutton
Surrey
SM2 5PT
United Kingdom
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| 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 | |
| Study acronym | EXPERT-C |
| Study objectives | 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(s) | Oxfordshire Research Ethics Committee A, approval was given on 05/04/2005 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Oxaliplatin, capecitabine, cetuximab. |
| Primary outcome measure | 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 study start date | 01/09/2005 |
| Completion date | 01/09/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 164 |
| Key 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 |
| Key exclusion criteria | 1. Any contraindications to MRI (e.g. patients with pacemakers) 2. Medical or psychiatric conditions that compromise the patients 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 |
| Date of first enrolment | 01/09/2005 |
| Date of final enrolment | 01/09/2012 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Royal Marsden Hospital
Surrey
SM2 5PT
United Kingdom
SM2 5PT
United Kingdom
Sponsor information
Royal Marsden NHS Foundation Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Downs Road
Sutton
Surrey
SM2 5PT
England
United Kingdom
| Website | http://www.royalmarsden.nhs.uk/rmh |
|---|---|
"ROR" |
https://ror.org/0008wzh48 |
Funders
Funder type
Industry
Professor Cunningham's Clinical Research Fund, Merck Pharmaceuticals (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? |
|---|---|---|---|---|---|
| Results article | results | 01/12/2013 | Yes | No | |
| Results article | results | 23/06/2014 | Yes | No |
