Phase Ib study of FOLFOXIRI plus ramucirumab as first-line treatment in patients with metastatic colorectal cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Metastatic Colorectal Cancer
PROVIDER: 2638530 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:The RANGE study (NCT02426125) evaluated ramucirumab (an anti-VEGFR2 monoclonal antibody) in patients with platinum-refractory advanced urothelial carcinoma (UC). Here, we use programmed cell death-ligand 1 (PD-L1) immunohistochemistry (IHC) and transcriptome analysis to evaluate the association of immune and angiogenesis pathways, and molecular subtypes, with overall survival (OS) in UC. Higher PD-L1 IHC and immune pathway scores, but not angiogenesis scores, are associated with greater ramucirumab OS benefit. Additionally, Basal subtypes, which have higher PD-L1 IHC and immune/angiogenesis pathway scores, show greater ramucirumab OS benefit compared to Luminal subtypes, which have relatively lower scores. Multivariable analysis suggest patients from East Asia as having lower immune/angiogenesis signature scores, which correlates with decreased ramucirumab OS benefit. Our data highlight the utility of multiple biomarkers including PD-L1, molecular subtype, and immune phenotype in identifying patients with UC who might derive the greatest benefit from treatment with ramucirumab. Please note that the RANGE clinical trial data generated in this study have been deposited at www.vivli.org. RANGE clinical trial data are available under restricted access to protect patient privacy, and access can be obtained by submitting a request. For details on submitting a request, see the instructions provided at www.vivli.org. For specific study details, see here: https://search.vivli.org/?search=NCT02426125.
2022-03-14 | GSE198269 | GEO
Project description:Interventions: Arm A: FOLFIRI plus ramucirumab (Rmab) treatment
- Rmab: 8 mg/kg/day1
- l-leucovorin (l-LV): 200 mg/m2/day1
- irinotecan (IRI): 180 mg/m2/day1
- bolus 5-FU: 400 mg/m2/day1
- infusional 5-FU: 2400 mg/m2/day1-3
Every 2 weeks
Arm B: FOLFOXIRI plus Rmab treatment
Induction therapy: 8 courses (maximum of 12 courses)
- Rmab: 8 mg/kg/day1
- IRI: 165 mg/m2/day1
- l-LV: 200 mg/m2/day1
- oxaliplatin (OX): 85 mg/m2/day1
- infusional 5-FU: 3200 mg/m2/day1-3
Every 2 weeks
Maintenance therapy: 5-FU/l-LV+Rmab, every 2 weeks
Primary outcome(s): Objective response rate
Study Design: randomized controlled trial, open(masking not used), active control, parallel assignment, treatment purpose
| 2614896 | ecrin-mdr-crc
Project description:Interventions: Arm A: FOLFIRI+Rmab treatment Rmab:8 mg/kg/day1 l-leucovorin (l-LV):200 mg/m2/day1 irinotecan (IRI): 180 mg/m2/day1 bolus 5-FU:400 mg/m2/day1 infusional 5-FU:2400 mg/m2/day1-3 Every 2 eeks
Arm B: FOLFOXIRI+Rmab treatment Induction therapy: 8 courses (maximum of 12 courses) Rmab:8 mg/kg/day1 IRI:165 mg/m2/day1 l-LV:200 mg/m2/day1 oxaaliplatin (OX):85 mg/m2/day1 infusional 5-FU: 3200 mg/m2/day1-3 Every 2 weeks Maintenance therapy 5-FU/l-LV+Rmab, every 2 week
Primary outcome(s): Objective response rate
Study Design: Parallel Randomized
| 2641746 | ecrin-mdr-crc
Project description:Gastric Cancer (GC) is one of the most serious cancers with high incidence and mortality all over the world. Chemotherapy hadn’t led to desirable effect and targeted therapy brings about a new stage to cancer treatment. Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer. It is well known that gold nanorod, a nontoxic biocompatible nanomaterial, is an especially promising candidate for cancer theranostic. In this study, Ramucirumab (Ab) were first modified by gold nanoparticles to enhance uptake efficiency. The simple Nano-delivery system had taken perfect aggregation effect in vivo even better than 5-fold Ab treatment. Gold nanomaterials, especially gold nanorod (AuNR), could induce direct cytotoxic effect to cancer cell in the presence of Ab, while Ab or gold nanoparticle themselves couldn’t lead to such direct killing effect even at an extremely high concentration. Transcriptomic and proteomic analyses revealed the mechanism of this direct cytotoxicity.
2021-08-06 | GSE181369 | GEO
Project description:BackgroundThe identification of molecular and genetic markers to predict or monitor the efficacy of bevacizumab (BV) represents a key issue in the treatment of metastatic colorectal cancer (mCRC).MethodsPlasma levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble VEGF receptor 2 (sVEGFR-2) and thrombospondin-1 (TSP-1) were assessed by ELISA assay at different time points in a cohort of 25 patients enroled in a phase II trial of GONO-FOLFOXIRI plus BV as first-line treatment of mCRC. VEGF: -2578A/C, -1498C/T, -1154A/G, -634C/G and 936C/T; and VEGFR-2: -604A/G, +1192C/T and +1719A/T, polymorphisms were assessed in a total of 54 patients.ResultsTreatment with GONO-FOLFOXIRI plus BV determined a prolonged and significant reduction in plasma free, biologically active VEGF concentration. Interestingly, VEGF concentrations remained lower than at baseline also at the time of PD. Conversely, PlGF levels increased during the treatment if compared with baseline, suggesting a possible role in tumour resistance; moreover, sVEGFR-2 increased at the time of PD, as well as TSP-1. No association of assessed polymorphisms with outcome was found.ConclusionOur study suggested the possible mechanisms of resistance to combined therapy in those patients with a progressive disease to be tested in ongoing phase III randomised studies.
| S-EPMC3078596 | biostudies-literature
Project description:Once randomisation has been completed, the study treatment should be started preferably immediately; at the latest within one week following randomisation.
The patients will be randomised in a ratio of 1:2 to the following two treatment arms.
Patients in both treatment arms will receive standard chemotherapy with FOLFOXIRI as background treatment, which can be de-escalated to FOLFIRI in case of toxicity.
Standard arm A:
The patient will be treated with FOLFOXIRI plus bevacizumab for up to 12 cycles (24 weeks) or until progression (if the latter occurs before completing the 12 cycles). Within the 12 cycles, the FOLFOXIRI plus bevacizumab regimen may be de-escalated, owing to toxicity, to FOLFIRI and bevacizumab at the treating physician’s discretion.
After 12 cycles of the study treatment, a switch to a maintenance regimen with a fluoropyrimidine (5-FU infusion or capecitabine) plus bevacizumab, administered until progression occurs, is recommended. The recommended maintenance phase of the study is not part of the study treatment. However, maintenance therapy will be counted as first-line therapy.
Experimental arm B:
The patient will be treated with FOLFOXIRI plus weekly administration of cetuximab for up to 12 cycles (24 weeks) or until progression (if the latter occurs before completing the 12 cycles). Within the 12 cycles, the FOLFOXIRI plus cetuximab regimen may be de-escalated owing to toxicity, to FOLFIRI and cetuximab at the treating physician’s discretion.
After 12 cycles, a switch to a maintenance regimen with 5-FU and cetuximab or with irinotecan and cetuximab, administered until progression occurs, is recommended. The recommended maintenance phase of the study is not part of the study treatment. However, maintenance therapy will be counted as first-line therapy.
| 2312043 | ecrin-mdr-crc
Project description:ImportanceRamucirumab, a human IgG 1 antibody against vascular endothelial growth factor receptor 2, has been shown to improve progression-free survival and overall survival in patients with advanced gastric cancer in the second-line setting.ObjectiveTo compare progression-free survival for S-1 and oxaliplatin plus ramucirumab with that for S-1 and oxaliplatin plus placebo in patients with advanced gastric cancer.Design, setting, and participantsThis phase 2, double-blind randomized clinical trial (RAINSTORM [First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab in Patients With Advanced Gastric Cancer]) was conducted from October 12, 2015, to April 11, 2018, at 36 sites in Japan, South Korea, and Taiwan. Participants were chemotherapy-naive patients (n = 189) with metastatic gastric or gastroesophageal adenocarcinoma. Analyses of the full analysis set and safety population were conducted between November 27, 2017, and June 4, 2018.InterventionsPatients randomized to the ramucirumab plus S-1 and oxaliplatin arm received S-1, 80 to 120 mg/d twice daily, on days 1 to 14 and oxaliplatin, 100 mg/m2, on day 1 with ramucirumab, 8 mg/kg, on days 1 and 8 in part A (21-day cycle). Patients randomized to the placebo plus S-1 and oxaliplatin arm received the same S-1 and oxaliplatin dosage as well as placebo on days 1 and 8 in part A. Eligible patients received second-line paclitaxel, 80 mg/m2, on days 1, 8, and 15 and ramucirumab, 8 mg/kg, on days 1 and 15 in part B (28-day cycle).Main outcomes and measuresThe primary end point was progression-free survival, analyzed using the stratified log-rank test; the hazard ratio (HR) was estimated using the stratified Cox proportional hazards regression model. Secondary end points included overall survival and adverse events.ResultsIn total, 189 patients were randomized and received treatment: 96 to the ramucirumab plus S-1 and oxaliplatin arm and 93 to the placebo plus S-1 and oxaliplatin arm. Among the 189 patients, 121 (64.0%) were male, and the median (range) age was 62.0 (26-84) years. Median progression-free survival was not prolonged in the ramucirumab plus S-1 and oxaliplatin arm compared with the placebo plus S-1 and oxaliplatin arm (6.34 [80% CI, 5.65-6.93] vs 6.74 [80% CI, 5.75-7.13] months; HR, 1.07; 80% CI, 0.86-1.33; P = .70). Median overall survival was 14.65 (80% CI, 12.39-15.67) months in the ramucirumab plus S-1 and oxaliplatin arm and 14.26 (80% CI, 13.83-17.31) months in the placebo plus S-1 and oxaliplatin arm (HR, 1.11; 80% CI, 0.89-1.40; P = .55). The most commonly reported grade 3 or higher treatment-emergent adverse events in the ramucirumab plus S-1 and oxaliplatin arm in part A were decreased neutrophil count (14 patients [14.6%]), hypertension (10 patients [10.4%]), and anemia (10 patients [10.4%]).Conclusions and relevanceIn this randomized clinical trial, the addition of ramucirumab to first-line S-1 and oxaliplatin treatment did not prolong progression-free survival or overall survival compared with S-1 and oxaliplatin alone among East Asian patients with advanced gastric cancer; no new safety signals for ramucirumab were identified.Trial registrationClinicalTrials.gov identifier: NCT02539225.
| S-EPMC6681552 | biostudies-literature
Project description: Not available
| S-EPMC8447873 | biostudies-literature
Project description:Intervention name : Ramucirumab
Dosage And administration of the intervention : Either ramucirumab DP (8 mg/kg) or placebo (a volume equivalent to that of ramucirumab DP), administered as an IV infusion over 60 (+10) minutes on Day 1 of each cycle; then a 1-hour observation period following the initial and second infusions of investigational product; followed by the FOLFIRI regimen indicated in the following bullets
Intervention name : Irinotecan (IRI)
Dosage And administration of the intervention : 180 mg/m2 administered intravenously over 90 (±10) minutes, 1 hour after the end of the infusion of investigational product (or immediately after the infusion of investigational product if no observation period is required) on Day 1 of each cycle; followed by
Intervention name : Folinic acid (FA)
Dosage And administration of the intervention : 400 mg/m2 administered intravenously over 120 (±10) minutes on Day 1 of each cycle; followed by
Intervention name : 5-Fluorouracil (5-FU)
Dosage And administration of the intervention : 400 mg/m2 bolus over 2 to 4 minutes administered intravenously immediately following completion of the FA infusion on Day 1 of each cycle; followed by 5-Fluorouracil (5-FU): 2400 mg/m2 administered intravenously over 46 to 48 hours (continuously) on Days 1 and 2 of each cycle
Control intervention name : null
| 2610580 | ecrin-mdr-crc
Project description:Primary objectives: To compare the objective response rate (ORR) according to RECIST 1.1 of treatment with FOLFOXIRI plus cetuximab versus treatment with FOLFOXIRI plus bevacizumab in BRAF-mutated patients.
| 2535112 | ecrin-mdr-crc