Plain English Summary
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
1387
Study information
Scientific title
A phase I/II study of Radiotherapy, Irinotecan, Capecitabine then Excision for locally advanced rectal cancer
Acronym
RICE (NWCOG - 2)
Study hypothesis
Phase I/II study. Phase I investigated the safety of preoperative neoadjuvant chemoradiation using radiotherapy combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery, determining the recommended dose.
Phase II of the study then used the recommended dose to assess the histological downstaging efficacy of this chemoradiation regimen, together with assessment of long-term survival end points and late radiation morbidity.
Ethics approval
First MREC approved on the 18th March 2004 (ref: 04/4/015)
Study design
Multicentre non-randomised interventional treatment trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
GP practices
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Colorectal Cancer; Disease: Rectum
Intervention
Capecitabine: orally at 650 mg/m^2 twice daily (b.d.) throughout radiotherapy including weekends
Irinotecan: 60 mg/m^2 intravenous (IV) once per week during the first 4 weeks of radiotherapy
Radiotherapy: 45 Gy in 25 daily fractions over 5 weeks
Follow-up length: 36 months
Intervention type
Drug
Phase
Phase II
Drug names
Irinotecan, capecitabine
Primary outcome measures
1. Determine safety and recommended dose of combination of radiotherapy, capecitabine and irinotecan (phase I only)
2. Histological pathological complete response rate (phase II only)
Secondary outcome measures
1. Long-term survival outcomes (phase II only)
2. Assessment of late morbidity (phase II only)
Overall trial start date
11/09/2003
Overall trial end date
20/12/2006
Reason abandoned
Eligibility
Participant inclusion criteria
1. Written informed consent given to participate in the trial
2. Male or female patients aged greater than or equal to 18 years old
3. World Health Organization (WHO) performance status 0, 1 or 2
4. Histologically confirmed previously-untreated carcinoma of the rectum with distal extent within 12 cm of the anal verge using a rigid sigmoidoscope
5. Deemed to be a candidate for preoperative downstaging chemoradiation due to: T3 disease on magnetic resonance imaging (MRI) scanning with disease less than or equal to 2 mm from the edge of the mesorectum or T4 disease on MRI scanning or any T3/T4 disease on MRI scanning with the distal extent of tumour less than or equal to 5 cm from the the anal margin
6. Adequate haematology: Neutrophil count greater than 1.5 x 10^9/l, platelet count greater than 100 x 10^9/l, Hb greater than 9 g/dl. The use of blood transfusions is allowed.
7. Adequate renal and hepatic function: serum creatinine = 1.5 x upper limit of normal (ULN), serum bilirubin = 1.25 x ULN, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase = 2.5 x ULN
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned sample size: 142; UK sample size: 142
Participant exclusion criteria
1. Previous systemic chemotherapy
2. Previous radiotherapy to the planned exposure area
3. Those unfit for resection because of metastases
4. Any severe concurrent medical condition which would make it undesirable, in the clinician's opinion, for the patient to participate in the trial or which would jeopardise compliance with the trial protocol
5. Patients with a calculated creatinine clearance of less than 50 ml/min
6. Patients with loss of continuity of the upper gastrointestinal (GI) tract or malabsorbtion
7. Patients who have suffered a myocardial infarction within last year and/or have unstable angina, arrythmia or cardiac failure
8. Pregnancy or lactation. Patients of child bearing potential not implementing adequate contraception.
9. Previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin
10. Subjects considered by the investigator to be at risk of transmitting any infection through blood or other body fluid including Acquired Immune Deficiency Syndrome (AIDS), or other sexually transmitted disease or hepatitis
11. Patient participation in other studies
12. Partial or complete bowel obstruction (though patients in whom this has been relieved with a defunctioning stoma, are permitted to enter the trial)
Recruitment start date
11/09/2003
Recruitment end date
20/12/2006
Locations
Countries of recruitment
United Kingdom
Trial participating centre
North Wales Cancer Treatment Centre
Rhyl
LL18 5UJ
United Kingdom
Sponsor information
Organisation
Conwy and Denbighshire NHS Trust (UK)
Sponsor details
Glan Clwyd District Hospital
Rhyl
Denbighshire
LL18 5UJ
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Pfizer Ltd (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Roche Ltd (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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
2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19690550
Publication citations
-
Results
Gollins SW, Myint S, Susnerwala S, Haylock B, Wise M, Topham C, Samuel L, Swindell R, Morris J, Mason L, Levine E, Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2)., Br. J. Cancer, 2009, 101, 6, 924-934, doi: 10.1038/sj.bjc.6605258.