Phase II clinical trial of the first-line Stop-and-Go modified FOLFOX6 and bevacizmab for patients with unresectable/recurrent colorectal cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2616726 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Interventions: After 8 cycles of mFOLFOX 6 plus bevacizumab, patients receive UFT/LV with bevacizumab (until 5 cycles are completed or disease progression). And then, patients receive modified FOLFOX6 plus bevacizumab until disease progression.
Patients receive mFOLFOX6 plus bevacizumab until disease progression.
Primary outcome(s): disease control survival
Study Design: Parallel Randomized
| 2618936 | ecrin-mdr-crc
Project description:This is a Phase 3, multicenter, randomized and double-blind study assessing the interchangeability between TRS003 and China-approved Bevacizumab (also called China-approved Avastin) for first-line treatment of patients with metastatic Colorectal Cancer (CRC), approximately 126 patients will be enrolled in this study. Patients who sign the informed consent, meet the eligibility criteria and are confirmed as non-progressors after lead-in treatment period with Bevacizumab in combination with modified FOLFOX6 chemotherapy for 6 cycles, will be randomized (1:1) to either the non-switching arm and receive Bevacizumab + modified FOLFOX6 for all subsequent cycles or to the switching arm and receive TRS003 alternating with Bevacizumab in combination with mFOLFOX6 until disease progression or intolerability.
| 2730925 | ecrin-mdr-crc
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: 6 cycles of bi-weekly mFOLFOX6 plus bevacizumab regimen is followed by 6 cycles of bi-weekly sLV5FU2 plus bevacizumab regimen. Agter the 12 cycle treatment, 6 cycles of bi-weekly mFOLFOX6 plus bevacizumab regimen is re-administred. Or 4 cycles of Tri-weekly XELOX plus bevacizumab regimen is followed by 4 cycles of Trii-weekly Capacitabine plus bevacizumab regimen. After the 8 cycle treatment, 4 cycles of Tri-weekly XELOX plus bevacizumab regimen is re-administred.
Primary outcome(s): median prpgression free survival (PFS)
Study Design: Single arm Non-randomized
| 2617525 | ecrin-mdr-crc
Project description:The patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received modified FOLFOX6. Responders and nonresponders were determined based on the best observed response at the end of the first-line treatment, mFOLFOX6. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133.
2013-01-03 | GSE19860 | GEO
Project description:Interventions: an omitted of bolus dose of fluorouracil of modified FOLFOX6 regimen,reduction of oxaliplatin dose of modified FOLFOX6 regimen, from 85 to 65 milligram per square meter;Experimental Drug,Active Comparator Drug;an omitted of bolus dose of 5-FU group,an oxaliplatin reduction group
Primary outcome(s): rate of recurrent neutropenia within 2 cycles of chemotherapy (mFOLFOX6 regimen) rate
Study Design: Randomized
| 2568181 | ecrin-mdr-crc
Project description:Oxidative phosphorylation (OXPHOS) is essential for the synthesis of the vast majority of ATP in eukaryotic cells. It is carried out by multi-protein assemblies that form the electron transport chain (ETC), which are coupled to the mitochondrial ATP synthase, which uses the proton gradient generated by the ETC to drive ATP synthesis. The assembly of the OXPHOS protein machinery requires the coordinated integration of proteins encoded in the nuclear and the mitochondrial genomes, imposing an additional layer of complexity. While the biogenesis of the individual OXPHOS complexes is well understood, it remains unknown how the assembly of the ETC and ATP synthase is coordinated to achieve the correct stoichiometry of the OXPHOS machinery. Here, we identify the mitochondrial regulatory hub for respiratory assembly (MiRA), which serves as a platform on which complex IV and complex V biogenesis are synchronised to ensure balanced assembly of the ETC and complex V. At the molecular level, this is achieved by a stop-and-go safeguarding mechanism: The novel mitochondrial protein Mra1 binds to and slows down complex IV assembly. Two Go signals are then required for assembly to proceed: Binding of the complex IV assembly factor Rcf2 and interaction with the mitoribosome, which translates the complex V subunit Atp9. Both Go signals induce the clipping and subsequent degradation of Mra1, relieving the molecular break and allowing parallel maturation of complexes IV and V. The absence of the stop-and-go safety mechanism results in the formation of immature complexes, decreased ATP levels and reduced cell viability. The antagonistic activities at MiRA provide a regulated orchestration of complex IV and V assembly which is essential to avoid the predominance of either complex and an unbalanced ratio of OXPHOS complexes, thus ensuring the correct stoichiometry of protein machineries encoded by two different genomes.
2024-02-16 | PXD044800 | Pride
Project description:Oxidative phosphorylation (OXPHOS) is essential for the synthesis of the vast majority of ATP in eukaryotic cells. It is carried out by multi-protein assemblies that form the electron transport chain (ETC), which are coupled to the mitochondrial ATP synthase, which uses the proton gradient generated by the ETC to drive ATP synthesis. The assembly of the OXPHOS protein machinery requires the coordinated integration of proteins encoded in the nuclear and the mitochondrial genomes, imposing an additional layer of complexity. While the biogenesis of the individual OXPHOS complexes is well understood, it remains unknown how the assembly of the ETC and ATP synthase is coordinated to achieve the correct stoichiometry of the OXPHOS machinery. Here, we identify the mitochondrial regulatory hub for respiratory assembly (MiRA), which serves as a platform on which complex IV and complex V biogenesis are synchronised to ensure balanced assembly of the ETC and complex V. At the molecular level, this is achieved by a stop-and-go safeguarding mechanism: The novel mitochondrial protein Mra1 binds to and slows down complex IV assembly. Two Go signals are then required for assembly to proceed: Binding of the complex IV assembly factor Rcf2 and interaction with the mitoribosome, which translates the complex V subunit Atp9. Both Go signals induce the clipping and subsequent degradation of Mra1, relieving the molecular brake and allowing parallel maturation of complexes IV and V. The absence of the stop-and-go safety mechanism results in the formation of immature complexes, decreased ATP levels and reduced cell viability. The antagonistic activities at MiRA provide a regulated orchestration of complex IV and V assembly which is essential to avoid the predominance of either complex and an unbalanced ratio of OXPHOS complexes, thus ensuring the correct stoichiometry of protein machineries encoded by two different genomes.
2024-02-16 | PXD044749 | Pride
Project description:Oxidative phosphorylation (OXPHOS) is essential for the synthesis of the vast majority of ATP in eukaryotic cells. It is carried out by multi-protein assemblies that form the electron transport chain (ETC), which are coupled to the mitochondrial ATP synthase, which uses the proton gradient generated by the ETC to drive ATP synthesis. The assembly of the OXPHOS protein machinery requires the coordinated integration of proteins encoded in the nuclear and the mitochondrial genomes, imposing an additional layer of complexity. While the biogenesis of the individual OXPHOS complexes is well understood, it remains unknown how the assembly of the ETC and ATP synthase is coordinated to achieve the correct stoichiometry of the OXPHOS machinery. Here, we identify the mitochondrial regulatory hub for respiratory assembly (MiRA), which serves as a platform on which complex IV and complex V biogenesis are synchronised to ensure balanced assembly of the ETC and complex V. At the molecular level, this is achieved by a stop-and-go safeguarding mechanism: The novel mitochondrial protein Mra1 binds to and slows down complex IV assembly. Two Go signals are then required for assembly to proceed: Binding of the complex IV assembly factor Rcf2 and interaction with the mitoribosome, which translates the complex V subunit Atp9. Both Go signals induce the clipping and subsequent degradation of Mra1, relieving the molecular brake and allowing parallel maturation of complexes IV and V. The absence of the stop-and-go safety mechanism results in the formation of immature complexes, decreased ATP levels and reduced cell viability. The antagonistic activities at MiRA provide a regulated orchestration of complex IV and V assembly which is essential to avoid the predominance of either complex and an unbalanced ratio of OXPHOS complexes, thus ensuring the correct stoichiometry of protein machineries encoded by two different genomes.
2024-02-16 | PXD044615 | Pride
Project description:Inhibitory control, the ability to stop or modify preplanned actions under changing task conditions, is an important component of cognitive functions. Two lines of models of inhibitory control have previously been proposed for human response in the classical stop-signal task, in which subjects must inhibit a default go response upon presentation of an infrequent stop signal: (1) the race model, which posits two independent go and stop processes that race to determine the behavioral outcome, go or stop; and (2) an optimal decision-making model, which posits that observers decides whether and when to go based on continually (Bayesian) updated information about both the go and stop stimuli. In this work, we probe the relationship between go and stop processing by explicitly manipulating the discrimination difficulty of the go stimulus. While the race model assumes the go and stop processes are independent, and therefore go stimulus discriminability should not affect the stop stimulus processing, we simulate the optimal model to show that it predicts harder go discrimination should result in longer go reaction time (RT), lower stop error rate, as well as faster stop-signal RT. We then present novel behavioral data that validate these model predictions. The results thus favor a fundamentally inseparable account of go and stop processing, in a manner consistent with the optimal model, and contradicting the independence assumption of the race model. More broadly, our findings contribute to the growing evidence that the computations underlying inhibitory control are systematically modulated by cognitive influences in a Bayes-optimal manner, thus opening new avenues for interpreting neural responses underlying inhibitory control.
| S-EPMC4801867 | biostudies-literature