Pre- and postoperative chemotherapy including Bevacizumab in potentially curable metastatic colorectal Cancer (mCRC). A multicenter, prospective Phase I/II academic trial.
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ABSTRACT:
DISEASE(S): patients With Histologically Confirmed Diagnosis Of Metastatic Colorectal Cancer (crc) Including Potentially Resectable Liver Metastases, Untreated Yet With Chemotherapy For Metastatic Disease
PROVIDER: 2520675 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Major attempt is being given to the potential of curing patients with metastatic colorectal cancer due to the recognition of dramatic change in survival figures achieved in palliative chemotherapy combination treatment protocols. Achieving resectablity rates in previously unresectable patients has been defined as study endpoint among other well known primary and secondary objectives. Curing metastatic colorectal cancer is most likely in resectable patients and therefore the logical next step after completion of chemotherapy combination studies (e.g. EORTC 40983) is the addition of targeted agents. Bevacizumab has the most valid data of improving outcome figures and was therefore chosen as additional agent. Safety of the combination with Xelox was demonstrated in the investigators pilot trial (Gruenberger JCO 2006, ASCO 2006, WCGC 2006, ESMO 2006), consequently response rate and resection rate will be the primary endpoints in this trial.
STUDY OBJECTIVES
Primary Objective The primary objective of this study is the Resectability (R0) rate after neoadjuvant Bevacizumab in potentially resectable mCRC.
Secondary Objectives The secondary objectives of this study include
* Feasibility with regards to GI bleeding and wound healing complications after surgery of liver metastases
* General safety
* Overall Response Rate (ORR)
* Recurrence Free Survival (RFS)
* Overall Survival (OS)
STUDY DURATION Recruitment is planned for 12 months. Patients will be treated for 6 cycles XELOX and 5 cycles Bevacizumab. Surgery will be performed 2 weeks after the last Capecitabine administration, allowing a time window of 5 weeks between the last Bevacizumab administration and surgery.
Therapy with 6 cycles of XELOX and Bevacizumab will be restarted 4-5 weeks after surgery.
With a Follow up period of 2 years after the last enrolled patient, in order to assess RFS and OS, the trial will last for approx. 3 years.
NUMBER OF CENTRES Four centres with a high level of experience in the surgery of liver metastases are planned to participate in this study.
SELECTION CRITERIA
Total Number of Patients and Target Population The planned total sample size for this study is 43 patients. Patients with potentially resectable metastatic colorectal cancer previously untreated for metastatic disease will be enrolled in this trial.
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2022-10-05 | PXD031929 | Pride
Project description:Background/Aims: Recurrence-free survival (RFS) following curative resection of hepatocellular carcinoma (HCC) in subjects with hepatitis C virus (HCV) infection is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized therapy. The goal of this study was to create a gene expression predictor of HCC recurrence in subjects with HCV. Methods: Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS. Results: The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGF-beta1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses. Conclusions: Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression signature of the predictor gives important insights into the pathobiology of HCC recurrence and used in design of the individualized therapy.
2010-04-14 | GSE17856 | GEO
Project description:Background/Aims: Recurrence-free survival (RFS) following curative resection of hepatocellular carcinoma (HCC) in subjects with hepatitis C virus (HCV) infection is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized therapy. The goal of this study was to create a gene expression predictor of HCC recurrence in subjects with HCV. Methods: Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS. Results: The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGF-beta1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses. Conclusions: Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression signature of the predictor gives important insights into the pathobiology of HCC recurrence and used in design of the individualized therapy. 43 tumor (JT) and 44 non-tumor (JNT) liver tissues surgically resected from patients with HCV-associated hepatocellular carcinoma; 8 non-tumor liver tissues (control samples, JC) surgically resected from HCV- or HBV-free patients with metastatic liver tumor. Inter-batch normalization was carried out using Distance Weighted Discrimination procedure. The supplementary file 'GSE17856_Readme.txt' contains a description of the replicates used for normalization. The 'GSE17856_US14702406_2514850*' files are the raw data files for the replicates.
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Project description:Primary objectives: Assessment of the efficacy of the combination of Bevacizumab with irinotecan- based chemotherapy (FOLFIRI) or oral capecitabine (XELIRI) in terms of resectability of the primary non-resectable liver metastases from metastatic colorectal cancer.
Primary endpoints: Assessment of effect of neoadjuvant combination of FOLFIRI or XELIRI chemotherapy regimen and bevacizumab on the resectability of liver metastases initially assessed as unresectable.
| 2522114 | ecrin-mdr-crc