C20
Conditions
Interventions
Group 1: Pre- and postoperative blood samples.
Standard 5-fluorouracil based radiochemotherapy schema followed by total mesorectal excision and adjuvant therapy.
Neoadjuvant:
5-FU 1000mg/m²
i.v. d 1-5 and d 29-33
Treatment-free interval before surgery: 5 weeks
Adjuvant (4 cycles):
5-FU 500mg/m², bolus, i.v. d 1-5 and d 29-33
Alternativ adjuvant (depending on the decision of the treating physician, e.g. ypN+
Glucose 5%, d 1 folinic acid: 400 mg/m² as 2h infusion, d 1
5-Fluorouracil: 2400 mg/m² as 46h infusion
Repeat on d 15, a total of 3 cycles (equivalent to 5 weeks).
Sponsors
Universitätsmedizin GöttingenGeorg-August-Universität
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Inclusion criteria
Inclusion criteria: - Aged 18 to 85 years, inclusive - Histologically confirmed advanced primary rectal cancer localized up to 12 cm above the anocutaneous line (determined with a rigid rectoscope), classified as T3/T4 or N+ carcinomas or with evidence for synchronous, but resectable distant metastases (liver or lung metastases) - No specific tumor treatment except colostomy due to tumor stenosis with ileus - WHO/ECOG status =2 - Adequate bone marrow function (WBC >3.0x10^9/L, neutrophils >1.5x10^9/L, thrombocytes >100x10^9/L, hemoglobin =10 g/dl) - Adequate liver function (bilirubin =2.0 mg/dl, SGOT, SGPT, AP, gamma-GT < three point five fold of upper level of normal range - serum creatinine < 1.5 mg/dl - Written and signed informed consent indicating the understanding of the investigational nature and the study protocol.
Exclusion criteria
Exclusion criteria: - Pregnant or lactating women - Men and women unwilling or unable to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment - Prolonged drug, medication or alcohol abuse - Previous chemotherapy (up to 2 years before diagnosis of rectal cancer) - Previous radiotherapy to the pelvic area - Simultaneous therapy with other anti-cancer drugs - Participation in a clinical trial in the period 30 days prior to inclusion - Patients (man and woman) who are not able or willing to accept treatment and follow-up care according to trial protocol - Patients (man and woman) with uncontrolled, serious physical or mental diseases, e.g.: instable cardiac disease in spite of medical treatment, myocardial infarction during the last 3 months prior to start of trial participation + neurological or psychiatric dysfunction including dementia or seizure disorder + Disseminated infection or sepsis + Disseminated intravascular coagulopathy + Symptomatic neuropathia (NCI CTC =2) - Patients with secondary malignancies except basal cell carcinoma of the skin or carcinoma in situ of the cervix, which have been successfully treated. (The inclusion of patients with other tumors that were successfully treated and no recurrence within the last 3-5 years should be discussed before registration in the trial) - Chronic diarrhea (>grade 1 according NCI CTCAE) - Allergic reaction to platin-derivates or study medication - Simultaneous treatment with sorivudin and analogous - Known Dihydropyrimidine dehydrogenase deficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The efficacy of the pretherapeutically determined response prediction using a reliable and robust panel of biomakers (gene expression signature) is assessed by several clinicopathological parameters after preoperative RCT and TME-surgery that indicate response and toxicity (ypN-status, pCR, tumorregression-grading, R-status, toxicity). Timepoint for measuring the geneexpression signature is the time of diagnosis (pretreatment biopsy); several immunhistochemical biomarkers (Thymidylatesyntahse, Survivin, HER-2) will be determined in the pretreatment biopsy as well as at the time of resection in the residual tumor tissue. | — |
Secondary
| Measure | Time frame |
|---|---|
| - R0-rate of resection - post-operative 30-day mortality - post-operative morbidity (esp. rate of anastomotic insufficiencies) - post-operative late complications (defecation problems, anastomotic, stenoses, loss of sphincter function) - quality of TME-surgery - acute and late toxicity of the chemotherapy according to the CommonToxicity Criteria of the National Cancer Institute (vs 4.0) - DSF after 2 and 3 years (local and/or distant recurrences) - cumulative incidence of local relapses and distant metastases - overall CSS after 3 and 5 years - quality of life according to the EORTC-Questionnaire QLQ-30 (3.0) and Wexner-Score has to filled out before the first treatment, at the end of treatment and 12, 36 and 60 months after surgical intervention. | — |
Countries
Germany
Contacts
Public ContactJohanna Kreutzer
Universitätsmedizin GöttingenGeorg-August-Universität
Outcome results
None listed