Multicenter phase II study of FOLFIRI and bevacizumab as second-line treatment in advanced or recurrent colorectal cancer.
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2617305 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Interventions: Patients receive modified FOLFOX6 with bevacizumab (Treatment will be continued to 24 cycles unless the disease progression, unacceptable toxicity, or consent withdrawal.).
Primary outcome(s): Efficacy: Response rate
Study Design: Single arm Non-randomized
| 2616982 | ecrin-mdr-crc
Project description:Interventions: Patients receive FOLFIRI with bevacizumab fixed 5mg/kg. (Treatment will be continued unless the disease progression, unacceptable toxicity, or consent withdrawal.) Definision of UGT1A1 polymorphisms groups: The homozygous group is patient with homozygous genotype of UGT1A1*28/*28 or UGT1A1*6/*6, with combined heterozygous genotypes of UGT1A1*28 and UGT1A1*6. The heterozygous group is patient with heterozygous genotype of either UGT1A1*28 or UGT1A1*6. The wild group is patients with no UGT1A1*28 and UGT1A1*6 mutation. CPT-11 dosage is wild and heterozygous:CPT-11 150mg/m2 homozygous:CPT-11 100mg/m2
Primary outcome(s): 1)incidence of adverse events 2)frequency of severe toxicity
Study Design: Single arm Non-randomized
| 2620216 | ecrin-mdr-crc
Project description:Sadanandam et al. (2013) recently published a study based on the use of microarray data to classify colorectal cancer (CRC) samples. The classification claimed to have strong clinical implications, as reflected in the paper title: “A colorectal cancer classification system that associates cellular phenotype and responses to therapy”. They defined five subtypes: (i) inflammatory; (ii) goblet-like; (iii) enterocyte; (iv) transit-amplifying; and (v) stem-like. Based on drug sensitivity data from 21 patients, they also reported that the so-called stem-like subtype show differential sensitivity to FOLFIRI. This is the key result in their publication, since it implies a direct relation between the subtype and the choice of CRC therapy (i.e. FOLFIRI response). However, our analyses using the same drug sensitivity data and results from additional patients showed that the CRC classification reported by Sadanandam et al. is not predictive of FOLFIRI response.
2014-09-10 | GSE54483 | GEO
Project description:scRNAseq of mouse colorectal organoids in FOLFIRI tratment
| PRJEB52817 | ENA
Project description:The aim of the experiment is to elucidate changes in tumor heterogeneity upon chemotherapy treatment. The experiment includes non-treated samples, samples right after chemotherapy treatment (FOLFIRI) and organoids recovered from FOLFIRI. It was conducted in two different genetic backgrounds, AKP (Apc KO, KrasG12D and P53 KO) and APS (Apc KO, P53 and Smad4KO). In addition to that, the organoids carry an inducible Cre-ERT2 knock-in allele in the mex3a locus. Upon 4-OH-Tamoxifen induction, Mex3a cells will recombine the tracing allele stop-TdTomato, enabling the tracing of this subpopulation. To understand the fate of the traced cells, samples right after chemotherapy and in the recovery setting were sorted based on their tomato expression. This enables a single cell tracing experiment.
2022-05-13 | E-MTAB-11145 | biostudies-arrayexpress
Project description:This is a prospective, multi-center, randomized study evaluating the efficacy and safety of fruquintinib combined with chemotherapy vs bevacizumab combined with chemotherapy as second-line treatment in patients with metastatic colorectal cancer. Patients will receive fruquintinib+ FOLFIRI or bevacizumab+FOLFIRI as the second-line treatment. After receiving 4-6 months of second-line treatment, patients who achieve disease control will receive fruquintinib + capecitabine or bevacizumab+ capecitabine as maintenance treatment. All patients will be treated until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal.
| 2749552 | ecrin-mdr-crc
Project description:Sadanandam et al. (2013) recently published a study based on the use of microarray data to classify colorectal cancer (CRC) samples. The classification claimed to have strong clinical implications, as reflected in the paper title: “A colorectal cancer classification system that associates cellular phenotype and responses to therapy”. They defined five subtypes: (i) inflammatory; (ii) goblet-like; (iii) enterocyte; (iv) transit-amplifying; and (v) stem-like. Based on drug sensitivity data from 21 patients, they also reported that the so-called stem-like subtype show differential sensitivity to FOLFIRI. This is the key result in their publication, since it implies a direct relation between the subtype and the choice of CRC therapy (i.e. FOLFIRI response). However, our analyses using the same drug sensitivity data and results from additional patients showed that the CRC classification reported by Sadanandam et al. is not predictive of FOLFIRI response. We used the classification algorithm to obtain CRC subtypes from our samples. Then we tested the subtype-drug response association performing a retrospective study.
2014-09-10 | E-GEOD-54483 | biostudies-arrayexpress
Project description:In CRC, 1) to identify epigenetic changes at inter-tumor and intra-tumor level, and 2) to relate intra-tumor clonality to clinical, molecular and histopathologic parameters. From 79 FFPE tumors, 3 different regions were macrodissected: invasive front (IF), digestive tract surface (DTS) and central bulk (CB). Clinical, molecular, and histopathologic parameters were stablished. Epigenetic analysis was performed using Infinium 450K beadchip (Illumina) and R statistics. Intra-tumor regions clustered together by patient. The biggest epigenetic changes were in IF vs DTS/CB. By patient, the most often divergent region was IF (49.4%) comparing with DTS and CB (25.3% in both). It did not correlate with histopathologic, molecular and clinical parameters.Epigenetic clonality is higher at intra-tumor level. The highest changes are observed in IF vs DTS/CB. No association with histopathologic, molecular, and clinical characteristics was found. Cohort of CRC patients (N=17) who recieved quemotherapy (FOLFIRI)
2016-08-16 | GSE81472 | GEO
Project description:Purpose of the study: the goal of this study was to use Next-generation sequencing to investigate the gene expression profile of skeletal muscle from mice exposed to chemotherapy (Folfiri) for up to 5 weeks. Methods: Standard methods were used for polyA mRNA-seq library construction, EZBead preparation and Next-Gen sequencing, based on Life Technologies SOLiD5000xl system. Briefly, one microgram total RNA per sample was applied for library preparation. PolyA mRNA was first captured using the standard protocol of Dynabeads® mRNA DIRECT™ Micro Kit (Life Technologies, #61021). Following the enrichment of polyA mRNA, the cDNA library was prepared and barcoded per sample using the standard protocol of SOLiD Total RNA-seq Kit (Life Technologies, #4445374). Each barcoded library was quantified by Bioanalyzer High Sensitivity DNA chip (Agilent, #5067-4626) and pooled in equal molarity. EZBead preparation, bead library amplification, and bead enrichment were then conducted using Life Technologies EZ Bead™ E80 System (Life technologies, #4453095). Approximately four hundred forty million library-enriched beads per lane were deposited onto a SOLiD5500xl FlowChip (6 lanes/chip). Finally sequencing by ligation was carried out using standard single-read, 5’-3’ strand-specific sequencing procedure (75b-read) on SOLiD5500xl Sequencer. The resulting 75 bp solid reads were mapped to Mus musculus mm9 reference genome using in-house mapping pipelines that utilizes bfast-0.7.0a [67]. In brief, using our RNA-seq pipeline, low quality reads and reads mapped to rRNA/tRNAs were first discarded. The remaining reads were mapped to reference genome mm9 and a splice-junction library, respectively; the genomic and splice-junction library mapping were merged at the end. The gene based expression levels were calculated using bamutils from NGSUtils based on the RefSeq gene annotation of mm9. Differential expression of genes across different treatments was determined with edgeR Results: Gene expression profiling, performed by means of RNA-Sequencing analysis, identified a limited number of genes that were significantly modulated (False Discovery Rate < 0.05) following Folfiri administration. Interestingly, the pathway analysis showed marked down-regulation of the regulators of mitochondrial metabolism Ucp1, Cidea1 and Acot2, as well as the marker of muscle cell proliferation/pluripotency Fhl3 . Further, we found increased expression of regulators of lipid metabolism and transport (such as Fabp1, Apoa1, Apob, Apoa2, Alb, Prkcz and Scd2) as well as acute phase response proteins (such as Alb, Fga and Fgb), and members of the PPAR signaling and markers of the Energy metabolism (such as Dnah5) were reported . Conclusions: Our study represents the first gene expression profiling of muscle from mice exposed to chemotherapy. The findings from our study identified several signaling pathways that were modulated following chemotherapy administration. These results will contribute to identify new modulators of muscle wasting associated with Folfiri administration, that might also represent putative new targets of interventions.
2016-05-18 | GSE80473 | GEO
Project description:Mex3a is an RNA binding protein of unknown function. To elucidate the contribution of Mex3a to tumoral heterogeneity, Mex3a KO organoids engineered by CRISPR were sequenced in three different conditions. Live organoids (DAPI negative) were sorted in Control, after 2 days of FOLFIRI and after 5 days of treatment. Two WT organoids (parental and a derived clone) and two KO (KO1 and KO2, two independent clones) were used for this experiment.
2022-05-16 | E-MTAB-11146 | biostudies-arrayexpress