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-Fluorouracil-based Standard Radiochemotherapy Followed by Total Mesorectal Excision. (TransValid-A)
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|ClinicalTrials.gov Identifier: NCT03034473|
Recruitment Status : Active, not recruiting
First Posted : January 27, 2017
Last Update Posted : October 16, 2018
The objective of the TransValid-KFO179/GRCSG-Trial-A is the validation of potential biomarkers. These are predictive (Prediction of probability of response to a certain therapy) / prognostic (predicting long-term outcome) microarray-based gene expression signatures and immunohistochemically evaluated biomarkers. The evaluation was done within the KFO179 (www.kfo179.de) - the validation is implemented in this trial.
Therefore tumor material of patients undergoing standard radiochemotherapy will be analyzed from pretreatment biopsies an residual tissue from the resection specimen after surgery. This validation and the biomaterial asservation will be incorporated into clinical routine in all participating centers as a model for the treatment of solid tumors. The obtained biomarkers with a predictive and prognostic power will be used to develop an algorithm to predict patients at high risk of local and distant cancer recurrence.
|Condition or disease||Intervention/treatment||Phase|
|Locally Advanced Rectal Cancer||Other: Translational Research and multimodal treatment||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||200 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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.|
|Study Start Date :||August 2011|
|Estimated Primary Completion Date :||May 2020|
|Estimated Study Completion Date :||October 2020|
Blood and tissue samples during therapy
Collection of blood and tissue samples during preoperative multimodal treatment (Radiochemotherapy (RCTx) followed by total mesorectal excision (TME) and Chemotherapy (CT)) in rectal cancer.
Other: Translational Research and multimodal treatment
Blood/biopsy samples (tumor & mucosa) are taken pretherapeutically. Blood samples (serum & plasma) are drawn at 11 time points during RCTx (e.g. for analysis of 5-FU metabolism, genomic DNA extraction). After pathohistological workup of the TME specimen, the formalin-fixed material will be transferred to the central biobank of KFO179. Blood samples (plasma & serum) will be drawn during 5y-follow-up. Treatment (based on CAO/ARO/AIO-94- and CAO/ARO/AIO-04-phase-III trials of the GRCSG):
Preoperative RCT: 28x1.8 Gy (total: 50.4 Gy, 5 fractions per week on d1-d38) combined with 5-FU (1000 mg/m2/d) as 120 h civ during 1st and 5th week.
TME-surgery is performed 6 weeks after RCTx. 4 to 8 weeks after surgery, patients receive either 4 cycles 5-FU (500 mg 5-FU/m2 iv, d1-5, repeat d 29-33) or 3 cycles (6 single appl.) of FOLFOX regimen [(400 mg FA/m2, 2-h civ, d 1; 100 mg oxaliplatin/m2, 2-h civ in 500 ml Glucose 5%, d 1; 2400 mg 5-FU/m2 as 46-h civ) on d1+d15, d30+d45 and d60+d75].
- Number of patients with histopathologically confirmed complete remission (pCR) (ypT0N0 R0) after preoperative RCTx related to pretherapeutically determined gene expression signature predicting tumor response to RCTx. [ Time Frame: 1 year after surgery ]
The efficacy of the pretherapeutically determined response prediction using a reliable and robust panel of biomarkers (gene expression signature) is assessed by several clinicopathological parameters after preoperative RCTx and TME-surgery that indicate response and toxicity (ypN-status, pCR, tumor regression-grading, R-status, toxicity).
Timepoint for measuring the gene expression signature is the time of diagnosis (pretreatment biopsy); several immunohistochemical biomarkers (Thymidylatesynthase, Survivin, HER-2) will be determined in the pretreatment biopsy as well as at the time of resection in the residual tumor tissue.
- R0-rate of resection [ Time Frame: 30 days after surgery based on histopathological findings and reports ]The resection status will be classified by the pathologists according to the established UICC-TNM-Classification (R0 vs R1 vs R2 resection status)
- post-operative 30-day mortality [ Time Frame: 30 days after surgery ]
- post-operative morbidity (esp. rate of anastomotic insufficiencies) [ Time Frame: 30 days after surgery ]
- post-operative late complications (defecation problems, anastomotic, stenoses, loss of sphincter function) [ Time Frame: up to 5 years after surgery ]
- Quality of TME-surgery according to M.E.R.C.U.R.Y classification [ Time Frame: 30 days after surgery based on surgical and histopathological findings/reports ]The quality of total mesorectal excision (TME) will be classified by the surgeons (intraoperatively according to M.E.R.C.U.R.Y criteria: good vs moderat vs poor as published in national guidelines) and independently by the pathologists (on the resected specimen according to the well established M.E.R.C.U.R.Y criteria: good vs moderate vs poor).
- acute and late toxicity of the chemotherapy according to the CommonToxicity Criteria of the National Cancer Institute (CTC) (vs 4.0) [ Time Frame: up to 5 years after therapy ]
- Disease free survival (DSF) after 2 and 3 years (local and/or distant recurrences) [ Time Frame: up to 3 years after surgery ]
- Cumulative incidence of local relapses and distant metastases [ Time Frame: up to 5 years after surgery ]
- Overall cancer specific survival (CSS) after 3 and 5 years [ Time Frame: up to 5 years after surgery ]
- Quality of life (QL) according to the EORTC-Questionnaire QLQ-30 (3.0) [ Time Frame: up to 5 years after surgery ]The EORTC-Questionnaire QLQ-30 (3.0) have to be completed at the following timepoints: before first treatment (baseline), at the end of treatment (30 days after last intervention or application) and during follow-up (12, 36 and 60 months after surgical intervention). The outcome measures at the end of treatment, 12,36,60 months after surgery will be compared to baseline. EORTC-Life Quality (LQ)-Questionnaire and Wexner Score-Questionnaire will be analysed separately.
- Wexner-Score-Questionnaire [ Time Frame: up to 5 years after surgery ]The Wexner-Score-Questionnaire have to be completed at the following timepoints: before first treatment (baseline), at the end of treatment (30 days after last intervention or application) and during follow-up (12, 36 and 60 months after surgical intervention). The outcome measures at the end of treatment, 12,36,60 months after surgery will be compared to baseline. EORTC-LQ-Questionnaire and Wexner Score-Questionnaire will be analysed separately.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03034473
|University Medical Center Goettingen|
|Gottingen, Lower Saxony, Germany, 37075|
|Principal Investigator:||Torsten Liersch, MD, Prof.||University Medical Center Goettingen|
|Study Director:||Michael Ghadimi, MD, Prof.||University Medical Center Goettingen|