Translational validation study to examine KFO179-1 biomarker scores for the prediction and prognosis of advanced primary resectable rectal cancer stages UICC II-IV, with a 5-FU-based standard radiochemotherapy followed by total mesorectal excision.

Recruitment & Eligibility

Status: Complete

Sex: All

Target Recruitment: 200

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

- 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

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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). <br>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 Outcome Measures

Name	Time	Method
-R0-rate of resection<br>-post-operative 30-day mortality<br>-post-operative morbidity (esp. rate of anastomotic insufficiencies)<br>-post-operative late complications (defecation problems, anastomotic, stenoses, loss of sphincter function)<br>-quality of TME-surgery <br>-acute and late toxicity of the chemotherapy according to the CommonToxicity Criteria of the National Cancer Institute (vs 4.0)<br>-DSF after 2 and 3 years (local and/or distant recurrences)<br>-cumulative incidence of local relapses and distant metastases<br>-overall CSS after 3 and 5 years<br>-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.<br>