Surgery alone In low rectal cancer
| ISRCTN | ISRCTN02406823 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN02406823 |
| Protocol serial number | CRT/LARC/ABM/v2.1 |
| Sponsor | Morriston Hospital (UK) |
| Funder | Funding decision awaited from Cancer Research UK (July 2014) |
- Submission date
- 14/04/2013
- Registration date
- 06/06/2013
- Last edited
- 09/04/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Contact information
Scientific
Department of Surgery
Singleton Hospital
Swansea
SA2 8QA
United Kingdom
| Phone | +44 (0)1792 285 459 |
|---|---|
| Dean.Harris2@wales.nhs.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Multicentred randomised controlled feasibility trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Multicentre randomised phase II feasibility study evaluating neoadjuvant chemoradiotherapy plus surgery with Surgery Alone In LOw Rectal cancer |
| Study acronym | SAILOR |
| Study objectives | Current hypothesis as of 24/02/2014: To explore the feasibility of phase III through: Primary objective to test willingness of eligible patients to be randomised to a surgery-alone arm Secondary objectives to estimate the change in quality of life with omission of CRT in resectable low rectal cancer; to test whether omission of CRT for resectable locally advanced low rectal cancer changes oncological safety measured by rate of surgical margin involvement, local recurrence and systemic recurrence at 2 years. Previous hypothesis: The trial has a dual hypothesis. The first hypothesis is that the Health Related Quality of Life in patients having surgery-alone is significantly better than patients who receive chemoradiation before surgery. The second hypothesis is that in there is no significant difference in the rates of surgical margin involvement when chemoradiation is omitted for selected patients with locally advanced rectal cancer, thus ensuring the safety of this selective approach. On 24/02//2014 the following changes were made to the trial record: 1. The public title was changed from 'Pilot study comparing neoadjuvant chemoradiotherapy plus surgery and surgery alone in locally advanced rectal cancer' to 'Surgery Alone In LOw Rectal cancer' 2. The scientific title was changed from 'Multicentred randomised controlled trial comparing neoadjuvant chemoradiotherapy plus surgery and surgery alone in locally advanced rectal cancer: a pilot study' to 'Multicentre randomised phase II feasibility study evaluating neoadjuvant chemoradiotherapy plus surgery with Surgery Alone In LOw Rectal cancer' 3. The anticipated start date was changed from 01/01/2014 to 01/10/2014 4. The anticipated end date was changed from 01/01/2016 to 01/10/2018 5. The target number of participants was changed from 60 to 80 6. The sources of funding field was changed from 'Awaiting decision from National Institute for Social Care and Health Research (NISCHR), Research for Patient and Public Benefit Wales (RfPPB Wales) - UK' to 'Funding decision awaited from Cancer Research UK (July 2014)'. |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Rectal cancer |
| Intervention | Schedule of Treatment Standardised radiotherapy: pre-operative radiotherapy with 45 Gy in 25 daily fractions over 5 weeks concurrent with either continuous-infusion 5-FU (225 mg/m2/day throughout the course of radiation therapy) 7 days a week for 5.5 weeks or capecitabine orally (PO) twice daily 5 days a week for 5.5 weeks. Formation of defunctioning colostomy before neoadjuvant chemoradiotherapy is permissible in the situation of severe symptoms at the discretion of the recruiting clinician. Assessment of response to CRT: Subsequent surgery is to be performed 8-12 weeks after completion of chemoradiotherapy. Patients should be restaged at 6 weeks after completion of CRT (minimum of CT thorax/abdomen/pelvis and MRI pelvis; endorectal ultrasound and examination under anaesthesia permitted depending on local policy). If complete clinical response (CCR) to CRT is suspected then patients are required by the protocol to undergo APER surgery as originally planned. See Criteria for Premature Withdrawal if this is not considered appropriate. Surgery-The abdominal phase of the abdominoperineal excision can be performed by either laparoscopic or open approach at discretion of the surgeon. The patient positioning for the perineal phase can be either supine or prone according to surgeon preference. A cylindrical perineal excision of the tumour, taking the levator ani (pelvic floor) musculature widely at their origins, is an essential study requirement. The technique of perineal reconstruction is at the discretion of the surgeon. This may include primary closure, use of a biological implant or plastic surgical reconstruction (myocutaneous/fasciocutaneous flap). |
| Intervention type | Other |
| Primary outcome measure(s) |
Current primary outcome measures as of 24/02/2014: |
| Key secondary outcome measure(s) |
Current secondary outcome measures as of 24/02/2014: |
| Completion date | 30/06/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 80 |
| Total final enrolment | 3 |
| Key inclusion criteria | Current inclusion criteria as of 24/02/2014: 1. Age 18 years and older 2. Histologically confirmed rectal adenocarcinoma 3. Radiologically measurable or clinically evaluable disease 4. Low rectal cancer, defined as within 6cm of anal verge on rigid sigmoidoscopy and considered to require abdominoperineal resection (APR) rather than restorative procedure (anterior resection) 5. Potentially resectable local disease by surgery alone with clear CRM (where visible on MRI) or predicted surgical resection margin (where CRM absent in distal tumours) as determined by MRI 6. Clinical disease stage (MRI+/- endorectal US): 6.1. cT3a/b (<10 mm) disease within 6 cm of anal verge; or for tumours at/below level of puborectalis 6.2. through full thickness of muscularis propria (cT2) disease at level of puborectalis 7. Involvement of internal anal sphincter or intersphincteric space without extension into adjacent levator plate, 8. TanyN1 (resectable) 9. WHO Performance status 0, 1, or 2 10. Neutrophil count ≥ 1,500/mm³ 11. Platelets ≥ 100,000/mm³ 12. Haemoglobin > 80 g/L 13. Total bilirubin ≤ 1.5x ULN 14. AST & ALT ≤ 3 x ULN 15. Creatinine ≤ 1.5 x ULN 16. Negative pregnancy test 17. Patient of child-bearing potential willing to employ adequate contraception 18. Willing to return to enrolling medical site for all study assessments 19. No other invasive malignancy ≤ 5 years prior to registration 20. No concurrent disease that, in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study 21. No chemotherapy within 5 years prior to registration (hormonal therapy is allowable if the disease-free interval is ≥ 5 years) 22. No prior pelvic radiation Previous inclusion criteria: 1. Aged 18 years and older 2. Pathologically confirmed rectal adenocarcinoma 3. Radiologically measurable or clinically evaluable disease 4. Low rectal cancer, defined as within 6cm of anal verge on rigid sigmoidoscopy and considered to require abdominoperineal excision (APER) 5. Potentially resectable local disease by surgery alone with clear margins as determined by MRI 6. Clinical disease stage (MRI+/- endorectal US): 6.1. T3a/b/c disease 6.2. T4 disease with sole involvement of internal/external sphincter/ adjacent (<10mm) levator plate or posterior wall of vagina 6.3. TanyN1 (resectable) 7. WHO Performance status 0, 1, or 2 8. Neutrophil count ≥ 1,500/mm³ 9. Platelets ≥ 100,000/mm³ 10. Haemoglobin > 8.0 g/dL 11. Total bilirubin ≤ 1.5x ULN 12. AST & ALT ≤ 3 x ULN 13. Creatinine ≤ 1.5 x ULN 14. Negative pregnancy test 15. Patient of child-bearing potential willing to employ adequate contraception 16. Willing to return to enrolling medical site for all study assessments 17. No other invasive malignancy ≤ 5 years prior to registration 18. No concurrent disease that, in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study 19. No chemotherapy within 5 years prior to registration (hormonal therapy is allowable if the disease-free interval is ≥ 5 years) 20. No prior pelvic radiation |
| Key exclusion criteria | Current exclusion criteria as of 24/02/2014: 1. Preoperative chemoradiotherapy absolutely indicated, for example MRI-predicted CRM/MRF involvement (<1 mm) by primary or nodal disease, or otherwise unresectable disease; 2. cT3c or d (>10 mm); 3. Adjacent organ involvement at entry (prostate, seminal vesicles, sacrum or coccyx; T4b) requiring multivisceral resection/ pelvic exenteration; 4. For low tumours at level of puborectalis sling: lateral extension of tumour into external anal sphincter or beyond puborectalis sling into levator plate; 5. Extramural vascular invasion on MRI; 6. Early stage rectal cancer (T1, T2 above level of levators) unless node positive; 7. Locally perforated disease (T4a); 8. Fistulating disease (vagina, perianal skin, adjacent hollow organ); 9. Disease extrusion through anus; 10. cN2 disease; 11. Lateral pelvic/ para-aortic lymphadenopathy (>10 mm by size criteria); 12. Unresectable metastatic disease (M1) (potentially resectable disease permitted); 13. Previous pelvic radiotherapy; 14. Unfit for major surgery; 15. Pregnancy; 16. Contraindication to MRI (metal implants etc); 17. Contraindication to 5-FU based chemotherapy (including drug interactions); 18. WHO Performance Status 3 or 4; 19. Unwilling to consent to trial participation Previous exclusion criteria: 1. Preoperative chemoradiotherapy absolutely indicated, for example predicted CRM involvement (<2 mm) by primary or nodal disease, or otherwise unresectable disease; 2. Adjacent organ involvement (prostate, seminal vesicles, sacrum or coccyx; T4b) requiring multivisceral resection/pelvic exenteration; wide (>10mm) levator involvement 3. Early stage rectal cancer (T1, T2) unless node positive 4. Locally perforated disease (T4a) 5. Disease extrusion through anus 6. Lateral pelvic/ paraaortic lymphadenopathy 7. Metastatic disease (M1) 8. Previous pelvic radiotherapy 9. Pregnancy 10. Contraindication to 5-FU based chemotherapy 11. WHO Performance Status 3 or 4 12. Unwilling to consent to trial participation Criteria for Premature Withdrawal 1. Withdrawal of consent 2. Failure to meet inclusion criteria (delayed) 3. Development of irresectable metastatic disease 4. Development of irresectable primary tumour after randomisation 5. Change in surgical procedure following chemoradiotherapy. In the event of significant tumour regression a sphincter-saving operation (low anterior resection) may be considered more appropriate by the responsible clinician than a sphincter-excising APR procedure. |
| Date of first enrolment | 01/10/2014 |
| Date of final enrolment | 31/03/2019 |
Locations
Countries of recruitment
- United Kingdom
- Wales
- Ireland
Study participating centre
SA2 8QA
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 21/11/2016 | Yes | No | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
09/04/2019: The total final enrollment has been added.
16/11/2018: The following changes were made:
1. The recruitment end date was changed from 01/10/2018 to 31/03/2019.
2. The overall trial end date was changed from 01/10/2018 to 30/06/2019.
3. The intention to publish date was added.
20/10/2017: Publication reference added.
09/09/2016: Cancer Help UK lay summary link added.
