Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors
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ABSTRACT:
DISEASE(S): Colorectal Neoplasms,Neoplasms
PROVIDER: 2049493 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Intervention1: Sutent (Sunitinib malate; sponsor code SU011248).: The sunitinib intended starting dose will be 15 mg/m2/day (not to exceed 50 mg/day. Intra-patient dose escalation of sunitinib will be allowed after completion of Cycle 1. Dose escalation will be in increments of 7.5 mg/m2, up to a maximum dose of 30 mg/m2 (not to exceed 50 mg/day). A cycle of therapy is considered to be 42 days, with the reporting period for each cycle being Day 1 to Day 42. For all patients, sunitinib will be dosed intermittently [4 weeks on study drug followed by 2 weeks off therapy. In the absence of progressive disease, patients may receive up to 18 cycles of sunitinib therapy for up to 24 months, so maximum duration of treatment according to the protocol is 2 years.
Control Intervention1: Nil: Nil
Primary outcome(s): Pharmacokinetic parameters of sunitinib and its main active metabolite (SU012662) including total plasma exposure (AUC24) and oral clearance (CL/F).Timepoint: Descriptive statistics for observed and dose-corrected (where appropriate) PK data will be reported for all patients with at least one PK observation by presenting the population size, arithmetic mean, standard deviation, percent coefficient of variation (CV%), median, minimum, maximum values at the end of the study.
| 2576443 | ecrin-mdr-crc
Project description:To evaluate the antitumor activity of SU011248 in advanced, imatinib mesylate-resistant gastrointestinal stromal tumor (GIST) when administered on a continuous daily dosing schedule
| 2014803 | ecrin-mdr-crc
Project description:To gain insights into the mechanisms of dihydroberberine, sunitinib and dihydroberberine plus sunitinib on inhibition to A549 cells, we have employed whole genome microarray expression profiling as a discovery platform to identify different genes between dihydroberberine, sunitinib and dihydroberberine plus sunitinib-treated sample and control.
2015-06-26 | GSE70282 | GEO
Project description:To gain insights into the mechanisms of dihydroberberine, sunitinib and dihydroberberine plus sunitinib on inhibition to A549 cells, we have employed whole genome microarray expression profiling as a discovery platform to identify different genes between dihydroberberine, sunitinib and dihydroberberine plus sunitinib-treated sample and control. A549 cells were cultivated in the absence or presence of 25?mol/L dihydroberberine, 2?mol/L sunitinib, 25?mol/L dihydroberberine plus 2?mol/L sunitinib for 48 h, followed by the Agilent Whole Human Genome Oligo Microarray
2015-06-26 | E-GEOD-70282 | biostudies-arrayexpress
Project description:Transcriptome analysis was used to identify gene expression changes during development of sunitinib resistance in a renal cell carcinoma patient-derived xenograft (PDX) model. During the response phase, tumors exhibited a 91% reduction in volume, characterized by induction of TNFRSF1A, TNFAIP3, NFKB2, CCL2, CCL20, BIRC3, and MOAP1. Ingenuity Pathway Analysis indicated decreased expression of cell survival genes during tumor response to sunitinib. In this model, after 4 weeks of treatment, tumors developed resistance despite continued administration of the tyrosine kinase inhibitor (TKI) sunitinib (40 mg/kg/d p.o.). Resistance was associated with increased expression of VEGFA, EPO, IL-8, ANGPT2, TNFRSF12, MAPK3/7, MAPKBP1, and increased cell survival genes, suggesting activation of angiogenesis and MAPK/ERK pathways. Tumor lysate mRNA evaluated for murine gene expression to examine the contribution of host effects, indicated that tumor response was associated with downregulation of immune cell trafficking, cellular movement, and inflammatory response genes. During tumor escape, genes associated with cellular movement, inflammatory response, and immune cell trafficking were strongly induced, along with intratumoral accumulation of myeloid derived suppressor cells (MDSC), indicating a role for host factors during emergence of sunitinib resistance. The same PDX model was used to assess anti-tumor efficacy of sunitinib combined with MEK inhibitor (MEKi) PD-0325901 (4 mg/kg/d p.o.) using different schedules. The most effective treatment regimen was either continuous treatment with both drugs or switching from sunitinib to PD-0325901 monotherapy at d30, which reduced tumor volume by 78.6% (p=0.0241) and 88.5% (p=0.0068), respectively. The combination of MEKi with TKI (sunitinib, axitinib, or pazopanib) suppressed levels of phospho-MEK1/2 and phospho-ERK1/2, and decreased intratumoral MDSC. Thus, continuous treatment with sunitinib alone did not maintain tumor response, and addition of a MEKi abrogated resistance leading to prolonged survival.
2015-12-17 | GSE76068 | GEO
Project description:Transcriptome analysis was used to identify gene expression changes during development of sunitinib resistance in a renal cell carcinoma patient-derived xenograft (PDX) model. During the response phase, tumors exhibited a 91% reduction in volume, characterized by induction of TNFRSF1A, TNFAIP3, NFKB2, CCL2, CCL20, BIRC3, and MOAP1. Ingenuity Pathway Analysis indicated decreased expression of cell survival genes during tumor response to sunitinib. In this model, after 4 weeks of treatment, tumors developed resistance despite continued administration of the tyrosine kinase inhibitor (TKI) sunitinib (40 mg/kg/d p.o.). Resistance was associated with increased expression of VEGFA, EPO, IL-8, ANGPT2, TNFRSF12, MAPK3/7, MAPKBP1, and increased cell survival genes, suggesting activation of angiogenesis and MAPK/ERK pathways. Tumor lysate mRNA evaluated for murine gene expression to examine the contribution of host effects, indicated that tumor response was associated with downregulation of immune cell trafficking, cellular movement, and inflammatory response genes. During tumor escape, genes associated with cellular movement, inflammatory response, and immune cell trafficking were strongly induced, along with intratumoral accumulation of myeloid derived suppressor cells (MDSC), indicating a role for host factors during emergence of sunitinib resistance. The same PDX model was used to assess anti-tumor efficacy of sunitinib combined with MEK inhibitor (MEKi) PD-0325901 (4 mg/kg/d p.o.) using different schedules. The most effective treatment regimen was either continuous treatment with both drugs or switching from sunitinib to PD-0325901 monotherapy at d30, which reduced tumor volume by 78.6% (p=0.0241) and 88.5% (p=0.0068), respectively. The combination of MEKi with TKI (sunitinib, axitinib, or pazopanib) suppressed levels of phospho-MEK1/2 and phospho-ERK1/2, and decreased intratumoral MDSC. Thus, continuous treatment with sunitinib alone did not maintain tumor response, and addition of a MEKi abrogated resistance leading to prolonged survival. Study was comprised of three experimental groups (pre-treatment, response, escape). All tumors came from the same PDX model. There were four biological replicates in each group. Four mice were used, with each of the 3 groups per mouse. There were no control or reference samples.
2015-12-17 | E-GEOD-76068 | biostudies-arrayexpress
Project description:Tyrosine kinase activity profiling of metatstatic malignant melanoma and normal skin tissue samples was performed using peptide kinase arrays. All samples were run in triplicates with and withouth inhbitor PLX4032 and Sutent Malate in order to identify how tyrosine kinases responds to kinase inhibitor treatment, ex vivo.
2013-01-17 | E-MTAB-1245 | biostudies-arrayexpress
Project description:RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with sunitinib malate may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving sunitinib malate together with combination chemotherapy works as front-line therapy in treating patients with metastatic rectal cancer that cannot be removed by surgery.
| 2074960 | ecrin-mdr-crc
Project description:Abstract Background: High-grade serous ovarian carcinoma (HGSOC) frequently develops resistance to platinum-based chemotherapy such as cisplatin, leading to high mortality. Sunitinib, a multi-target Receptor tyrosine kinase inhibitor, has shown potential in the treatment of ovarian carcinoma (OC). However, the synergistic effects between cisplatin and sunitinib, and the sensitization mechanism of sunitinib in HGSOC are not yet understood. Methods: The anti-tumor effects of sunitinib on HGSOC cells were assessed using CCK-8, EdU, colony formation, wound healing, Transwell, and flow cytometry assays. RNA sequencing was performed on sunitinib-treated cells, followed by differential expression, enrichment, and protein-protein interaction network (PPI) analyses. Genes on cisplatin sensitivity were predicted using the CellMiner and GEPIA3 databases. Synergy between sunitinib and cisplatin was evaluated using SynergyFinder 3.0, and DNA damage was assessed by γ-H2AX expression. Results: Sunitinib significantly inhibited proliferation, migration, and invasion in HGSOC cells, while further inducing cell cycle arrest, promoting necrosis. Besides, sunitinib downregulated critical DNA damage repair pathways, including homologous recombination, fanconi anemia, and base excision repair. Furthermore, sunitinib synergizes with cisplatin in HGSOC cells, enhancing DNA damage compared to monotherapy. Additionally, we screened out 25 sunitinib-downregulated core genes (SDCs). Drug-sensitivity analyses showed that higher SDCs expression was significantly associated with cisplatin resistance in OC. Notably, in cisplatin-resistant HEY-A8/DDP cells, sunitinib displayed stronger cytotoxicity than cisplatin. Conclusion: Sunitinib induces cell-cycle arrest and necrosis. In addition, sunitinib synergized with cisplatin and enhanced cisplatin sensitivity by impairing DNA repair pathways. Drug-sensitivity analyses showed that SDCs are associated with cisplatin resistance in OC, suggesting that sunitinib may help overcome cisplatin chemoresistance. Notably, sunitinib retains substantial cytotoxic activity in cisplatin-resistant cells. Together, these findings suggest that the sunitinib–cisplatin combination is a promising strategy to overcome cisplatin resistance in HGSOC.
2026-02-09 | GSE318963 | GEO
Project description:Sunitinib resistance creates a major clinical challenge for the treatment of advanced clear cell renal cell carcinoma (ccRCC) and functional and metabolic changes linked to sunitinib resistance are not fully understood. We sought to characterize the molecular and metabolic changes induced by the development of sunitinib resistance in ccRCC by developing and characterizing the transcriptome of two human ccRCC cell lines resistant to sunitinib.
2024-04-17 | GSE216494 | GEO