Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Dr Ruby AL-Mokhtar
ORCID ID
Contact details
Cardiff University
Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
United Kingdom
-
al-mokhtarr@cardiff.ac.uk
Additional identifiers
EudraCT number
2010-023083-40
ClinicalTrials.gov number
NCT01263171
Protocol/serial number
11709
Study information
Scientific title
A Phase II study of neoadjuvant chemotherapy given before short course of preoperative radiotherapy (SCPRT) as treatment for patients with MRI-staged operable rectal cancer at high risk of metastatic relapse
Acronym
COPERNICUS
Study hypothesis
Approximately 15,000 patients are diagnosed with rectal cancer in the UK per annum, 4800 of which would be considered operable. The current standard of care for these patients, is to deliver a short course of preoperative radiotherapy (SCPRT) followed by immediate surgery and postoperative chemotherapy to prevent relapse. However, several studies have highlighted poor compliance due to postoperative surgical morbidity and reduced performance status. There is thus a strong argument to evaluate pre-operative chemotherapy in patients with operable rectal cancer in order to increase patient tolerance, achievable dose intensity and minimize micrometastases by addressing this issue earlier on in treatment.
The overall aim of this study is to assess the feasibility of introducing eight weeks of oxaliplatin/5-Fluorouracil (OxMdG) chemotherapy prior to SCPRT and immediate surgery. Feasibility will be assessed as the percentage of patients undergoing surgery as well as assessing; the dose intensity achieved, treatment toxicities, postoperative morbidity/mortality and activity using histological measures of response in the resected specimen. If deemed to be feasible, the Phase II treatment regime will be taken forward to a Phase III trial where it will be compared against standard practice of SCPRT alone followed by immediate surgery.
Ethics approval
Research Ethics Committee for Wales, ref: 12/WA/0051
Study design
Non-randomised interventional treatment
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Colorectal cancer
Intervention
Neoadjuvant chemotherapy, Patients who have enrolled into the COPERNICUS study will be treated with four, two weekly cycles of oxaliplatin and fluorouracil prior to short course pre-operative radiotherapy followed by surgical removal of the tumour and adjuvant chemotherapy.
Intervention type
Drug
Phase
Phase II
Drug names
Fluorouracil, oxaliplatin
Primary outcome measure
The proportion of patients who commence neoadjuvant chemotherapy who then undergo surgical resection
Secondary outcome measures
1. Acute and late toxicity
2. Histological assessment of downstaging efficacy
Overall trial start date
01/05/2012
Overall trial end date
01/04/2013
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patient 18 years old or older
2. Tumour biopsy with histopathological confirmation of rectal adenocarcinoma
3. Inferior aspect of disease (primary tumour, mesorectal tumour deposits or extra-mural vascular invasion) is not less than 4 cm from anal verge on digital examination and pelvic MRI scan
4. Superior aspect of disease is not more superior than the anterior aspect of the S1/S2 interspace on pelvic sagittal MRI scan
5. Further MRI defined inclusion criteria include: Mesorectal fascia is not threatened or involved (i.e. tumour is > 1mm from mesorectal fascia) Primary tumour is: T3a-b (mesorectal primary tumour invasion seen = 5 mm beyond muscularis propria) in the presence of either:
5.1. Extra-mural vascular invasion or
5.2. Mesorectal lymph nodes(s)/tumour deposit(s) with irregular border or mixed signal intensity any T3c (primary tumour invasion seen >5mm beyond muscularis propria)-T4a (invasion of visceral peritoneum for tumours with a component above peritoneal reflection) Low tumours should not involve levator ani (i.e. there is >1 mm gap between tumour and levator ani) or anal sphincters
6. No evidence of established metastatic disease on CT of chest and abdomen. (Patients with equivocal lesions determined at MDT are eligible)
7. Patient with measurable disease at the baseline visit
8. The patient is a candidate for systemic therapy with OxMdG chemotherapy in the opinion of the primary oncologist treating the patient
9. ECOG Status: 0-1
10. Bloods: Adequate bone marrow, hepatic, renal and metabolic function (assessed within 14 days prior to consent):
10.1. Haemoglobin = 9 g/dL, leucocyte count = 3 x 109/L, neutrophil count =1.5 x109/L and platelet count =100 x109/L
10.2. Total bilirubin = 1.5 x ULRR, alkaline phosphatase = 5 x ULRR, and serum transaminase (either AST or ALT) =2.5 x ULRR
10.3. Estimated creatinine clearance = 50 ml/min (calculated according to Cockroft and Gault). (Confirmed with 24 hour urine creatinine clearance or EDTA if estimated creatinine clearance < 50 ml/min)
10.4. Calcium =LLRR
11. No known significant impairment of intestinal absorption (e.g. chronic diarrhoea, inflammatory bowel disease)
12. Baseline ECG showing no evidence of established or acute ischaemic heart disease (e.g. left bundle branch block, pathological q waves, ST elevation or ST-segment depression) and normal clinical cardiovascular assessment
13. Note, a defunctioning colostomy or ileostomy is permitted to relieve impending rectal obstruction or severe local bowel symptoms
14. Lower age limit 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
UK Sample Size: 62
Participant exclusion criteria
1. Disease threatening the mesorectal fascia (i.e. disease = 1 mm from mesorectal fascia whether this is primary tumour, extra-mural vascular invasion or tumour deposit with irregular border or mixed signal intensity)
2. Stage T4b cancer with invasion into adjacent organs or structures
3. Enlarged pelvic sidewall (internal iliac) lymph nodes considered to be involved
4. Unequivocal evidence of metastatic disease (includes resectable metastases)
5. Severe local bowel symptoms of tenesmus, frequency (at least baseline grade 3 diarrhoea) or incontinence that have not been relieved by a defunctioning colostomy/ileostomy.
6. Pelvic sepsis
7. Metallic colonic/ rectal stent in situ
8. Patient who has received previous pelvic radiotherapy
9. Patient with an uncontrolled infection
10. Pregnant, breast feeding or trying to conceive
11. Previous treatment with another investigational antitumoral therapy in the 30 days prior to beginning treatment (including chemotherapy, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloproteinase inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibodies, or other experimental drugs)
12. Patients with another previous or current malignant disease which in the judgement of the treating investigator is likely to interfere with treatment or the assessment of response.
13. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) = 1 year before enrollment
14. History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
15. Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment
16. Previous malignancies in the preceding five years except for:
-In situ cancer of the uterine cervix
-Adequately treated basal cell skin carcinoma
-Any early stage malignancy
Recruitment start date
01/05/2012
Recruitment end date
01/04/2013
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Cardiff University
Cardiff
CF14 4YS
United Kingdom
Sponsor information
Organisation
Cardiff University (UK)
Sponsor details
30-36 Newport Road
Cardiff
CF24 0DE
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
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
Basic results (scientific)
See https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-023083-40/results
Publication list