|- candidate number||1904|
|- NTR Number||NTR552|
|- Date ISRCTN created||14-feb-2006|
|- date ISRCTN requested||27-jan-2006|
|- Date Registered NTR||23-dec-2005|
|- Secondary IDs||2003 – 16 CKTO |
|- Public Title||Simply Capecitabine in rectal cancer after irradiation plus TME.|
|- Scientific Title||A Multicenter Phase III Randomised Trial comparing Total Mesorectal Excision with Pre-operative Radiotherapy with or without Post-operative Oral Capecitabine in the Treatment of Operable Primary Rectal Cancer.|
|- hypothesis||The overall survival in the arm treated without chemotherapy (TNM-stage II or III tumours) is expected to be approximately 60%. Assuming an improvement in overall survival from 60% to 70% in the arm treated with chemotherapy (TNM-stage II or III tumours), 840 patients are needed; 420 in each arm (alpha 0.05, two sided; power 0.90). |
|- Healt Condition(s) or Problem(s) studied||Tumour, Rectal cancer|
|- Inclusion criteria||1. Rectal adenocarcinoma confirmed by histological examination of the biopsy specimen, located below the level of S1/S2 on a barium enema, CT scan or MRI scan, or either located within 15 cm of the anal verge, measured during withdrawal of the flexible scope; |
2. Preoperative short term hypofractioned radiotherapy (5x5 Gy);
3. TME-surgery performed;
4. TNM-stage II (T3-T4, N0) or III (any T, N+) as defined by postoperative examina-tion of the resected specimen;
5. Start of chemotherapy treatment is possible within 6 weeks after surgery;
6. WHO performance score <= 2;
7. Patient is considered to be mentally and physically fit for chemotherapy as judged by the medical oncologist;
8. Age ≥ 18 years;
9. Written informed consent;
10. Adequate potential for follow-up.
|- Exclusion criteria||1. Evidence of macroscopic residual disease (R2);|
2. T1 or T2 tumour with the presence of micrometastasis without the presence of macrometastasis;
3. Contraindications to chemotherapy, including adequate blood counts (measured after recovery from surgery)
- white blood count ≥ 4.0 x 10x9/L
- platelet count ≥ 100 x 10x9/L
- clinically acceptable haemoglobin levels
- creatinine levels indicating renal clea- rance of ≥ 60 ml/min
- bilirubin < 25 µmol/l;
4. Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn’s disease or active Ulcerative colitis;
5. Concomitant malignancies, except for adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must be disease-free for at least 10 years;
6. Known DPD deficiency.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-okt-2004|
|- planned closingdate||1-sep-2007|
|- Target number of participants||840|
|- Interventions||Subjects will be randomised 1:1 to receive either 24 weeks of post-operative treat-ment (8 courses) with oral capecitabine twice daily, given on days 1-14 every 21 days versus no post-operative treatment (observation).|
|- Primary outcome||To investigate in rectal cancer patients, in a randomised fashion, whether post-operative chemotherapy leads to a substantial improvement in overall survival, when standardised TME-surgery and pre-operative radiotherapy and pathology are applied.|
|- Secondary outcome||1. To investigate in a randomised fashion whether post-operative chemotherapy leads to a substantial improvement in local and distant tumour control, when standardised TME-surgery, pre-operative radiotherapy and pathology are applied; |
2. Standardisation and quality control of TME-surgery and pathology.
|- Trial web site||http://www.dccg.nl/|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. C.J.H. Velde, van de|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. C.J.H. Velde, van de|
|- Sponsor/Initiator ||University Medical Center St. Radboud, Department of Medical Oncology 550, Dutch Colorectal Cancer Group (DCCG)|
(Source(s) of Monetary or Material Support)
|Koningin Wilhelmina Fonds (KWF), Roche Nederland BV|
|- Brief summary||Background:|
Of major concern in the treatment of rectal cancer is the development of local and distant recurrences. Local recurrence rates have been reduced by both TME-surgery and pre-operative hypofractioned radiotherapy. So far, chemotherapy has shown little or no effect in combination with conventional surgery in the prevention of distant recurrences and improvement of survival. This may in part be explained by the high rate of local recurrence, which might have masked the beneficial effect of chemotherapy. The role of adjuvant chemotherapy has never been tested in combination with standardised TME-surgery. In the CKVO 95-04 trial, the beneficial role of pre-operative, short-term radiotherapy has been confirmed in combination with standardised and quality-controlled TME-surgery and pathology. In this successor trial, the additional value of post-operative chemotherapy will be evaluated in the same setting.
Main objective: To investigate in a randomised fashion whether chemotherapy after standardised TME-surgery with pre-operative radiotherapy, leads to a substantial improvement in overall survival.
Secondary objective: To investigate in a randomised fashion whether post-operative chemotherapy leads to a substantial improvement in local and distant tumour control, when standardised TME-surgery with pre-operative radiotherapy and pathology are applied.
The issue of this trial will be studied through randomisation for yes/no post-operative chemotherapy; only patients with a TNM-stage II or III rectal adenocarcinoma without any macroscopical residual tumour are eligible for this randomisation. The lower margin of the tumour must have been located within 15 cm of the anal verge. TME-surgery must have been performed and all patients must have received preoperative radiotherapy with 5x5 Gy. Only patients with WHO performance status 2 or less and without contraindications to chemotherapy are eligible.
Pathological examination of the resected specimen must have been done according to the protocol of Quirke. If a patient is randomised for chemotherapy, 8 courses of capecitabine are given. Primary end-point will be overall survival and secondary endpoints will be overall recurrence rate (local + distant recurrence) and local and distant recurrence separately. All randomised patients will be followed for the end-points.
The overall survival in the arm treated without chemotherapy (TNM-stage II or III tumours) is expected to be approximately 60%. Assuming an improvement in overall survival from 60% to 70% in the arm treated with chemotherapy (TNM-stage II or III tumours), 840 patients are needed; 420 in each arm (alpha 0.05, two sided; power 0.90).
|- Main changes (audit trail)|
|- RECORD||23-dec-2005 - 5-jan-2010|