locally advanced rectal cancer MedDRA version: 14.1 Level: PT Classification code 10038050 Term: Rectal cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10038049 Term: Rectal cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Eloxatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OXALIPLATIN
CAS Number: 61825943
Concentration unit: mg/ml milligram(s)/millilitre
Concentration ty
Sponsors
EORTC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male or female patients with histologically proven adenocarcinoma of the rectum (tumour = 12 cm from the anal verge as assessed by rigid proctoscopy). ¨ Clinical tumour stage T3/4 or any node-positive disease (clinical stage according the TNM classification system (Appendix J), positive nodes as diagnosed on endorectal ultrasound and/or MRI). Tumour is staged by preferably a high resolution MRI. If MRI is not available, locoregional staging must be performed by computed tomography plus endorectal ultrasound. ¨ No evidence of metastatic disease (as evidenced by negative CT-scan of the chest and abdomen). ¨ The disease must be considered either resectable at the time of entry or expected to become resectable after preoperative chemoradiation. ¨ Age = 18 years. ¨ WHO/ECOG Performance Status = 2 ¨ No prior cytotoxic chemotherapy or radiotherapy for rectal cancer. ¨ No prior radiotherapy to the pelvis, for any reason. ¨ Presence of adequate contraception in fertile patients. Adequate methods of contraception are: intra-uterine device, hormonal contraception, condom use with spermicide. Pregnant or breastfeeding women are excluded from participation. ¨ Adequate bone marrow, hepatic and renal function: ¨ Haemoglobin = 10.0 g/dL (transfusions allowed to achieve or maintain levels), absolute neutrophil count = 1.5 x 109/L, platelet count = 100 x 109/L, ¨ ALAT, ASAT = 2.5 x ULN, ¨ Alkaline phosphatase = 2.5 x ULN, ¨ Total bilirubin = 1.5 x ULN, ¨ Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault) and ¨ Creatinine = 1.5 x ULN. ¨ Ability to swallow tablets. ¨ Patient must not have been treated with any investigational drug, agent nor procedure, (i.e. did not participate in another trial within 4 weeks) before entry in this trial. No previous (within the last 5 years) or concurrent malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the skin. ¨ No clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction within the last 12 months. ¨ No known allergy or any other adverse reaction to any of the study drugs or to any related compound. ¨ No known dihydropyrimidine dehydrogenase deficiency. ¨ No known significant impairment of intestinal resorption (e.g. chronic diarrhoea, inflammatory bowel disease). ¨ No pre-existing condition which would deter chemoradiotherapy or radiotherapy, i.e. fistulas, severe ulcerative colitis (particularly patients currently taking sulphasalazine), Crohn’s disease, prior adhesions. ¨ No peripheral neuropathy = grade 2 (according to CTCAE v3.0) ¨ No serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease. ¨ No organ allograft requiring immunosuppressive therapy. ¨ No requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine. ¨ No history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake. ¨ No psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (these conditions should be discussed with the patient before registration in the tr
Exclusion criteria
Exclusion criteria: -severe renal impairment (creatinine clearance below 30 ml/min) -pregnancy and lactation -hypersensitivity to capecitabine or 5-FU or to any of the excipients -patients with history of severe and unexpected reactions to fluoro pyrimidine therapy -patients with known dihydropyrimidine dehydrogenase (DPD) deficiency -patients with severe leucopenia, neutropenia and thrombocytopenia -severe hepatic impairment -concomittant use of sorivudine or its chemically related analogues such as brivudine -patients with known allergy against oxaliplatin or other platinum compounds -patients with impaired bone marrow function -patients with pre-excisting peripheral neuropathy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether the addition of oxaliplatin to preoperative fluoropyrimidine-based chemoradiation and postoperative fluoropyrimidine-based chemotherapy improves disease-free survival in patients with locally advanced rectal cancer. Disease-free survival is defined as the interval from randomization to loco-regional failure, metastatic recurrence, the appearance of a secondary colorectal cancer or death, whichever occurs first. ;Secondary Objective: secondary objectives are to compare the two treatment arms with respect to overall survival, loco-regional failure, distant failure, pathological down-staging (ypT0-2N0) rate, pathological complete remission (ypT0N0) rate, tumor regression grade, histopathological R0 resection rate, sphincter preservation rate, perioperative complication rate, toxicity (CTC). ;Primary end point(s): The primary endpoint is disease-free survival | — |
Countries
Belgium, France, Germany, United Kingdom
Contacts
Public ContactProject, Budget & Regulatory Dpt
EORTC
Outcome results
None listed