ARISTOTLE: a phase III trial comparing standard versus novel chemoradiation treatment (CRT) as pre-operative treatment for magnetic resonance imaging (MRI)-defined locally advanced rectal cancer
| ISRCTN | ISRCTN09351447 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN09351447 |
| EudraCT/CTIS number | 2008-005782-59 |
| Secondary identifying numbers | Version 6.1 |
- Submission date
- 28/10/2008
- Registration date
- 08/09/2009
- Last edited
- 03/10/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Contact information
Ms Rubina Begum
Public
Public
Cancer Research UK & UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom
| Phone | 020 7679 9514 |
|---|---|
| ctc.aristotle@ucl.ac.uk |
Study information
| Study design | Two-arm phase III multicentre randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| 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 | ARISTOTLE: Advanced Rectal study wIth Standard Therapy Or a novel agent, Total mesorectal excision (TME) and Long term Evaluation |
| Study acronym | ARISTOTLE |
| Study objectives | 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(s) | NRES Committee London - Riverside, 17/09/2010, ref. 10/H0706/65 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | 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 study start date | 22/09/2011 |
| Completion date | 29/12/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 600 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 25/10/2011 |
| Date of final enrolment | 29/06/2018 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
103 centres
-
United Kingdom
United Kingdom
Sponsor information
Cancer Research UK and UCL Cancer Trials Centre (UK)
Charity
Charity
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom
| Website | http://www.ctc.ucl.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/054225q67 |
Funders
Funder type
Charity
Cancer Research UK (CRUK) (UK) (ref: C19942/A10016)
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Planned publication in a high impact peer reviewed journal approximately 1 year after end of trial. |
| IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Other publications | Modeling Acute Chemoradiotherapy (CRT) Diarrhea Severity Using Automatically Contoured Small Bowel | 01/10/2023 | 03/10/2023 | Yes | No |
Editorial Notes
03/10/2023: Publication reference added.
09/08/2018: The protocol/serial number was changed from 6.0 to 6.1.
15/01/2018: The following changes were made to the trial record:
1. Trial website, ethics approval, publication plan, intention to publish date and participant level data were added.
2. Protocol number was changed from version 5.1 to 6.0.
3. Overall trial end date was changed from 25/10/2022 to 29/12/2023.
4. Intervention, primary outcome measures and secondary outcome measures were updated.
5. Ms Rubina Begum replaced Prof David Sebag-Montefiore as the primary study contact.
30/11/2017: The recruitment end date was changed from 25/10/2017 to 29/06/2018.
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.
