Condition category
Cancer
Date applied
28/10/2008
Date assigned
08/09/2009
Last edited
01/06/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Prof David Sebag-Montefiore

ORCID ID

Contact details

St James Institute of Oncology
Level 4
Bexley Wing
St. James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom

Additional identifiers

EudraCT number

2008-005782-59

ClinicalTrials.gov number

Protocol/serial number

Version 5.1

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

Not provided at time of registration

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

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 measures

Current 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 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

25/10/2022

Reason abandoned

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 109/L; platelets > 100 x 109/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

25/10/2017

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

http://www.ctc.ucl.ac.uk/

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

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

01/06/2016: the following changes were made to the trial record: 1. The overall trial start date was changed from 01/01/2010 to 22/09/2011. 2. The overall trial end date was changed from 01/01/2015 to 25/10/2022. 3. The target number of participants was changed from 916 to 600. 10/09/2009: the following changes were made to the trial record: 1. The overall trial start date was changed from 01/03/2009 to 01/01/2010. 2. The overall trial end date was changed from 01/03/2014 to 01/01/2015.