Locally advanced rectal cancer Cancer Malignant neoplasm of rectum
Conditions
Interventions
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 intrave
Sponsors
Cancer Research UK and UCL Cancer Trials Centre (UK)
Eligibility
Sex/Gender
All
Age
18 Years to 120 Years
Inclusion criteria
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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
United Kingdom
Contacts
Public ContactRubina Begum
Outcome results
None listed