Rectal cancer Cancer Rectal cancer
Conditions
Interventions
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
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 unde
Sponsors
Morriston Hospital (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
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 ( 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 ( 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 maligna
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 24/02/2014: 1. Preoperative chemoradiotherapy absolutely indicated, for example MRI-predicted CRM/MRF involvement (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 (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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 24/02/2014: This study will primarily test the feasibility of a phase III randomised study by measuring willingness of participants to be randomised; willingness of clinicians to recruit participants; and testing appropriateness of the proposed outcome measures, to include choice of QOL tools and measurement of response rates to questionnaires. The paired principal outcomes are: 1. Disease-specific quality of life measures using the EORTC QLQ-C30 and QLQ-CR29 tools. Quality of life will be assessed at the same timepoints between the groups (enrolment, prior to surgery, 1 month after surgery, and at 3 months, 6 months, 12 months, 18 months and 24 months) with a supplementary timepoint in group 1 (at end of chemoradiotherapy) 2. Circumferential Resection Margin (CRM) distance (as early surrogate marker for local recurrence when less than 1 mm) and both local and systemic recurrence rates at 2 years based on CT imaging. Previous primary outcome measures: The paired principal outcomes are: 1. Disease-specific quality of life measures, to include bowel, bladder and sexual function. The Quality of Life tools selected are FACT-C; EORTC QLQ-C30 and I-QOL (see supplementary files). Quality of life will be assessed at enrolment, at the end of chemoradiotherapy, prior to surgery, 1 month after surgery, and at 3 months, 6 months, 12 months, 18 months and 24 months. 2. Circumferential Resection Margin (CRM) distance (as early surrogate marker for local recurrence when less than 1mm). | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 24/02/2014: 1. Clinical endpoints: 1.1. Early disease-free survival at 2 years 1.2. Costs and consequences of neo-adjuvant CRT plus surgery compared with surgery alone through economic analysis and Patient Reported Outcome Measures (EQ-5D-5L); 2. Acute and late toxicity related to chemotherapy and/or radiotherapy: 2.1. EORTC Common Toxicity Criteria version 4 (2009), 2.2. RTOG/EORTC Late Morbidity Scoring Scheme 3. Rate of development of irresectable primary tumour after CRT; 4. Perioperative complication rates: 4.1. Organ specific (Cardiovascular, Respiratory, Renal/Urological, Gastrointestinal, Infectious/septic, abdominal wound related) 4.2. Rate of Perineal wound healing (at 3 months) 4.3. Transfusion requirement (within 30 days of surgery) 4.4. Return to theatre/reoperation 5. Length of stay (postoperative) 6. 30-day perioperative mortality 7. Time to commencement of adjuvant chemotherapy after surgery 8. Pathological outcomes to include: 8.1. T stage (TNM) 8.2. N stage (TNM) 8.3. Presence of extramural vascular invasion 8.4. Distance to circumferential resection margin 8.5. Distance to dentate line 8.6. Plane of mesorectal excision (mesorectal/ intramesorectal/ muscularis propria) and perineal excision (Levator/ sphincteric/ intrasphincteric) as proxy of surgical quality 8.7. Presence of specimen perforation 8.8. Tumour regression grade (in response to chemoradiotherapy) 8.9. Rate of pathological complete response Previous secondary outcome measures: 1. Acute and late toxicity related to chemoth | — |
Countries
Ireland, United Kingdom
Outcome results
None listed