Contact information
Type
Public
Primary contact
Ms Rubina Begum
ORCID ID
Contact details
Cancer Research UK & UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom
020 7679 9514
ctc.aristotle@ucl.ac.uk
Additional identifiers
EudraCT number
2008-005782-59
ClinicalTrials.gov number
Protocol/serial number
Version 6.1
Study information
Scientific title
ARISTOTLE: Advanced Rectal study wIth Standard Therapy Or a novel agent, Total mesorectal excision (TME) and Long term Evaluation
Acronym
ARISTOTLE
Study hypothesis
Some patients with rectal cancer benefit from receiving chemotherapy and radiotherapy before they have an operation to remove their cancers. This trial will determine whether the addition of a second drug (irinotecan) to the standard treatment of oral chemotherapy using capecitabine and radiotherapy will result in fewer cancer recurrences (regrowth) after the operation and if patients live longer.
Ethics approval
NRES Committee London - Riverside, 17/09/2010, ref. 10/H0706/65
Study design
Two-arm phase III multicentre randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
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
Locally advanced rectal cancer
Intervention
Current interventions (as of 15/01/2018):
Arm A: capecitabine 900 mg/m^2 orally twice daily Monday to Friday for five weeks with radiotherapy 45 Gy in 25 fractions.
Arm B: irinotecan 60 mg/m^2 intravenously (IV) once weekly, weeks 1 - 4 and capecitabine 650 mg/m^2 orally twice daily Monday to Friday for five weeks with radiotherapy 45 Gy in 25 fractions.
All patients will be followed up for 5 years after completion of chemoradiotherapy.
Previous interventions
Arm A: capecitabine 900 mg/m^2 orally twice daily Monday to Friday for five weeks with radiotherapy 45 Gy in 25 fractions.
Arm B: irinotecan 60 mg/m^2 intravenously (IV) once weekly, weeks 1 - 4 and capecitabine 650 mg/m^2 orally twice daily Monday to Friday for five weeks with radiotherapy 45 Gy in 25 fractions.
All patients will be followed up for 5 years.
Intervention type
Drug
Phase
Phase III
Drug names
Irinotecan, capecitabine
Primary outcome measure
Current primary outcome measures (as of 15/01/2018):
Disease free survival at 3 years after completion of chemoradiotherapy
Previous primary outcome measures as of 01/06/2016:
Disease free survival at 3 years
Previous primary outcome measures:
Disease free survival, assessed at four planned stages during the trial
Secondary outcome measures
Current secondary outcome measures (as of 15/01/2018):
1. Disease-specific survival
2. Loco-regional failure
3. Overall survival
4. Histopathologically confirmed circumferential resection margin (CRM) negative resection rate
5. Histopathological complete response pathological complete response (pCR) rate
6. Histopathologically quantitated tumour cell density
7. Surgical morbidity
8. Health-related Quality of Life (QoL) and functional outcome
9. Frequency and severity of adverse events
10. Compliance to trial treatment (radiotherapy, capecitabine and irinotecan)
Assessments weekly during treatment phase, then 1 and 4 weeks after completion of treatment, and then 4 - 6 weeks after completion of treatment.
Previous secondary outcome measures as of 01/06/2016:
1. Disease-specific survival
2. Loco-regional failure
3. Overall survival
4. Histopathologically confirmed circumferential resection margin (CRM) negative resection rate
5. Histopathological complete response pathological complete response (pCR)
6. Histopathologically quantitated tumour cell density
7. Surgical morbidity
8. Health-related Quality of Life (QoL) and functional outcome
Previous secondary outcome measures:
1. Disease-specific survival
2. Loco-regional failure
3. Overall survival
4. Histopathologically confirmed circumferential resection margin (CRM) negative resection rate
5. Histopathological complete response pathological complete response (pCR)
6. Surgical morbidity
7. Functional outcome
8. Quality of life
9. Resource use
Assessments weekly during treatment phase and then at 2 and 4 weeks after completion of treatment, and then 4 - 6 weeks after completion of treatment.
Overall trial start date
22/09/2011
Overall trial end date
29/12/2023
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current inclusion criteria as of 01/06/2016:
1. Diagnosis of primary rectal cancer
2. Histologically confirmed invasive adenocarcinoma
3. Pelvic MRI defined disease (one of the following):
3.1. Mesorectal fascia involved or breached
3.1.1. Includes involvement of adjacent organ
3.2. Mesorectal fascia threatened (tumour ≤ 1 mm from mesorectal fascia) includes:
3.2.1. Primary tumour ≤ 1 mm from mesorectal fascia or
3.2.2. Extra-mural vascular invasion ≤ 1 mm from mesorectal fascia or
3.2.3. Tumour deposit with irregular border and mixed signal intensity ≤ 1 mm from mesorectal fascia
3.3. Low tumours at/below level of levators where:
3.3.1. Tumour ≤ 1 mm from levator on two imaging planes or
3.3.2. Tumour through full thickness of muscularis propria or beyond at level of puborectalis sling or below or
3.3.3. Tumour involving the intersphincteric plane or
3.3.4. Tumour involving the external anal sphincter
3.3.5. Patients with enlarged pelvic side wall nodes are eligible only if they also meet at least one of the above criteria.
4. Superior extent of macroscopic tumour no higher than S1/2 junction on saggital MRI
5. ECOG performance status 0 or 1
6. Considered fit to receive all trial treatments
7. Bowel function controlled with ≤ 6 mg loperamide per day
8. Absolute neutrophil count > 1.5 x 10^9/L; platelets > 100 x 10^9/L
9. Serum transaminase < 3 x ULN
10. Adequate renal function (Cockcroft-Gault estimation ≥ 50 mL/min)
11. Bilirubin < 1.5 x ULN
12. Able to swallow oral medication
13. Willing and able to give informed consent and comply with treatment and follow-up schedule
14. Aged 18 or over
Previous inclusion criteria:
1. Mesorectal fascia involved
2. Mesorectal fascia threatened (tumour less than 1 mm from mesorectal fascia)
3. Low tumours arising less than 5 cm from the anal verge
4. Patients aged 18 years and over, both male and female patients
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
600
Participant exclusion criteria
Current exclusion criteria as of 01/06/2016:
1. Previous radiotherapy to the pelvis (including brachytherapy)
2. Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction within 6 months prior to randomisation)
3. Unequivocal evidence of metastatic disease (includes resectable metastases)
3.1. Patients with equivocal lesions (determined at MDT) are eligible
4. Major disturbance of bowel function (e.g. gross faecal incontinence or requiring > 6 mg loperamide each day)
5. History of another malignancy within the last 5 years except successfully treated non-melanoma cancer of skin or carcinoma in situ of uterine cervix
6. Known dihydropyrimidine dehydrogenase (DPYD) deficiency
7. Known Gilberts disease (hyperbilirubinaemia)
8. Taking warfarin that cannot be discontinued at least 7 days prior to starting treatment
9. Taking phenytoin or sorivudine or its chemically related anologues, such as brivudine
10. Gastrointestinal disorder which would interfere with oral therapy and its bioavailability
11. Pregnant, lactating, or pre menopausal women not using adequate contraception
12. Oral St John’s Wort therapy that cannot be discontinued at least 14 days prior to starting treatment
13. Unfit to receive any study treatment or subsequent surgical resection
Previous exclusion criteria:
1. Patients unable or unfit to receive all study treatment
2. World Health Organization (WHO) performance status greater than or equal to 2
3. Metastatic disease
4. Pregnant or lactating
Recruitment start date
25/10/2011
Recruitment end date
29/06/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
103 centres
-
United Kingdom
Sponsor information
Organisation
Cancer Research UK and UCL Cancer Trials Centre (UK)
Sponsor details
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom
Sponsor type
Charity
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (CRUK) (UK) (ref: C19942/A10016)
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned publication in a high impact peer reviewed journal approximately 1 year after end of trial.
IPD sharing statement
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.
Intention to publish date
31/12/2024
Participant level data
Other
Basic results (scientific)
Publication list