A phase II, randomized, double-blind, placebo-controlled trial evaluating efficacy and safety of namodenoson (CF102), an A3 adenosine receptor agonist (A3AR), as a second-line treatment in patients with Child-Pugh B (CPB) advanced hepatocellular carcinoma (HCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2503-2503 ◽  
Author(s):  
Salomon M. Stemmer ◽  
Nebojsa S. Manojlovic ◽  
Mihai Vasile Marinca ◽  
Petar Petrov ◽  
Nelly Cherciu ◽  
...  
Keyword(s):  
Liver Dysfunction ◽  
Subgroup Analysis ◽  
Objective Response ◽  
Second Line ◽  
Efficacy And Safety ◽  
Severe Liver ◽  
Double Blind ◽  
Advanced Hcc ◽  
End Point ◽  
Severe Liver Dysfunction

2503 Background: There is no established primary treatment for patients with advanced HCC and severe liver dysfunction (Child-Pugh B class; CPB), thus this representing a clear unmet need. Namodenoson, an A3AR agonist, showed promising preliminary results in this population in an open label phase 1/2 clinical study (NCT00790218), with median overall survival (OS) of 8.1 months. We present the results of a double blind, randomized phase 2, placebo-controlled study (NCT02128958), assessing the efficacy and safety of namodenoson as a second-line therapy of patients with advanced HCC and CPB class. Methods: Patients were randomized 2:1 to BID namodenoson (25 mg; n = 50) or placebo (n = 28) in 15 centers globally. Primary endpoint was OS and secondary endpoints were safety, progression-free survival (PFS), objective response (OR) and disease control rate (DCR). Assessment of OS and PFS was done by log rank test at a one final analysis when 75 deaths had occurred. Response was assessed by RECIST (local investigator) and mRECIST (central review). Results: The study did not meet the primary end point, with median OS 4.1 months (mo) for namodenoson vs. 4.3 mo for placebo (HR: 0.82). Pre-planned subgroup analysis of Child-Pugh 7 patients (n=56; namodenoson=34, placebo=21) showed median survival 6.8mo vs 4.3 mo [HR: 0.77 (95% CI 0.49-1.40)]. Similarly, for this subgroup of patients PFS was 3.5 mo vs 1.9 (HR=0.87). In terms of objective response, 3/34 patients assessed achieved OR (9%) with namodenoson vs 0% for placebo. Namodenoson was generally well-tolerated, with no treated patients being withdrawn for toxicity and no cases of treatment-related deaths. The most common adverse event (>10%) were anemia, abdominal pain, ascites, nausea, asthenia, fatigue, peripheral edema, and increased AST. Treatment-related grade 3 toxicities accounted for anemia, fatigue and hyponatremia. Conclusions: Namodenoson has demonstrated favorable clinical safety profile in patients with advanced HCC and severe liver dysfunction. Although the primary end-point was not met, the subgroup analysis showed a positive signal of efficacy for OS in patients with Child-Pugh 7. Both safety and efficacy results warrant testing this drug in a phase III trial. Clinical trial information: NCT02128958.

Effect of anlotinib in advanced small cell lung cancer (SCLC) patients relapsed within three months after second-line treatment: A subgroup analysis from a randomized, double-blind phase II trial (ALTER 1202).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9063-9063
Author(s):  
Jianhua Shi ◽  
Ying Cheng ◽  
Qiming Wang ◽  
Kai Li ◽  
Lin Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Subgroup Analysis ◽  
Objective Response ◽  
Small Cell ◽  
Line Treatment ◽  
Second Line ◽  
Small Cell Lung ◽  
Double Blind

9063 Background: Anlotinib had significantly improved progress-free survival (PFS) and overall survival (OS) of advanced small cell lung cancer (SCLC) patients received at least two lines chemotherapy in the ALTER 1202 trial. Here, we reported the effect of anlotinib in advance SCLC patients relapsed within 3 months after second-line treatment. Methods: The ALTER 1202 was a randomized, double-blind phase 2 trial including patients with advanced SCLC that received at least two previous lines of chemotherapy. Eligible patients were randomized in a 2:1 ratio to receive either anlotinib or placebo until tumor progression or unacceptable toxicity. The subgroup analysis assessed the effect of anlotinib in patients relapsed within 3 months after second-line treatment. The primary outcome was PFS. The secondary outcomes were OS, objective response rate (ORR), disease control rate (DCR) and safety. This trial was registered with ClinicalTrials.gov, number NCT03059797. Results: In the ALTER1202 trial, 67 patients in anlotinib group and 34 patients in placebo group relapsed within 3 months after second-line treatment. Among them, the median PFS was 3.98 months (95% confidence interval [CI], 2.79 to 4.24) with anlotinib versus 0.72 months (95% CI, 0.69 to 0.82) with placebo (hazard ratio [HR], 0.14; 95% CI, 0.08 to 0.26; P < 0.0001). Meanwhile, anlotinib significantly prolonged OS compared with placebo (7.29 months [95% CI, 6.51 to 10.51] versus 4.37 months [95% CI, 2.33 to 6.47]; HR, 0.42 [95% CI, 0.23 to 0.74]; P = 0.0059) in patients relapsed within 3 months after second-line treatment. ORR was 4.48% (3 PR) for anlotinib and 2.94% (1 PR) for placebo (P = 0.708). DCR was 73.13% for anlotinib and 11.76% for placebo (P < 0.0001). The most common adverse events were hypertension (38.81%), anorexia (28.36%), fatigue (22.39%) and Elevation of alanine aminotransferase (17.91%). Conclusions: Anlotinib improved PFS and OS in advanced SCLC patients relapsed within 3 months after second-line treatment and was well tolerated.

scholarly journals Subgroup analysis by prior anti-VEGF or anti-EGFR target therapy in FRESCO, a randomized, double-blind, Phase III tri1al

2020 ◽  
Author(s):  
Ruihua Xu ◽  
Shukui Qin ◽  
Weijian Guo ◽  
Yuxian Bai ◽  
Yanhong Deng ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Target Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Placebo Treatment ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Meaningful Improvement ◽  
Colorectal Cancer Patients

Background: FRESCO study demonstrated efficacy and safety of fruquintinib in metastatic colorectal cancer patients. Impact of prior targeted therapy (PTT) on efficacy and safety of fruquintinib was evaluated. Materials & methods: In this subgroup analysis of FRESCO trial, patients were divided into PTT and non-PTT subgroups, and efficacy and safety of fruquintinib were assessed, respectively. Results: In non-PTT subgroup, fruquintinib significantly prolonged overall survival (OS) and progression free survival (PFS) of patients compared with placebo. In PTT subgroup, the median OS and PFS of patients in fruquintinib arm was significantly higher than those in placebo. Treatment-emergent adverse events (TEAEs) rates were similar in both subgroups. Conclusion: Fruquintinib demonstrated clinically meaningful improvement in OS, PFS, objective response rate, and disease control rate with manageable TEAEs in both subgroups. ClinicalTrial Registration: NCT02314819 ( ClinicalTrials.gov )

scholarly journals Severe liver dysfunction complicating course of COVID-19 in the critically ill: multifactorial cause or direct viral effect?

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin Roedl ◽  
Dominik Jarczak ◽  
Andreas Drolz ◽  
Dominic Wichmann ◽  
Olaf Boenisch ◽  
...  
Keyword(s):  
Critically Ill ◽  
Liver Dysfunction ◽  
Critically Ill Patients ◽  
Severity Of Illness ◽  
University Hospital ◽  
Severe Liver ◽  
Saps Ii ◽  
Severe Liver Dysfunction ◽  
Global Threat ◽  
The University

Abstract Background SARS-CoV-2 caused a pandemic and global threat for human health. Presence of liver injury was commonly reported in patients with coronavirus disease 2019 (COVID-19). However, reports on severe liver dysfunction (SLD) in critically ill with COVID-19 are lacking. We evaluated the occurrence, clinical characteristics and outcome of SLD in critically ill patients with COVID-19. Methods Clinical course and laboratory was analyzed from all patients with confirmed COVID-19 admitted to ICU of the university hospital. SLD was defined as: bilirubin ≥ 2 mg/dl or elevation of aminotransferase levels (> 20-fold ULN). Results 72 critically ill patients were identified, 22 (31%) patients developed SLD. Presenting characteristics including age, gender, comorbidities as well as clinical presentation regarding COVID-19 overlapped substantially in both groups. Patients with SLD had more severe respiratory failure (paO2/FiO2: 82 (58–114) vs. 117 (83–155); p < 0.05). Thus, required more frequently mechanical ventilation (95% vs. 64%; p < 0.01), rescue therapies (ECMO) (27% vs. 12%; p = 0.106), vasopressor (95% vs. 72%; p < 0.05) and renal replacement therapy (86% vs. 30%; p < 0.001). Severity of illness was significantly higher (SAPS II: 48 (39–52) vs. 40 (32–45); p < 0.01). Patients with SLD and without presented viremic during ICU stay in 68% and 34%, respectively (p = 0.002). Occurrence of SLD was independently associated with presence of viremia [OR 6.359; 95% CI 1.336–30.253; p < 0.05] and severity of illness (SAPS II) [OR 1.078; 95% CI 1.004–1.157; p < 0.05]. Mortality was high in patients with SLD compared to other patients (68% vs. 16%, p < 0.001). After adjustment for confounders, SLD was independently associated with mortality [HR3.347; 95% CI 1.401–7.999; p < 0.01]. Conclusion One-third of critically ill patients with COVID-19 suffer from SLD, which is associated with high mortality. Occurrence of viremia and severity of illness seem to contribute to occurrence of SLD and underline the multifactorial cause.

Purine Analogs for Patients with Non-Hodgkin Lymphoma and Severe Liver Dysfunction

2018 ◽  
Vol 18 ◽  
pp. S291-S292
Author(s):  
Tamer Khashab ◽  
Ashley Manganiello ◽  
Julianne Hibbs ◽  
Thomas Oliver ◽  
Jonathan Doroshow ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Liver Dysfunction ◽  
Severe Liver ◽  
Non Hodgkin Lymphoma ◽  
Purine Analogs ◽  
Severe Liver Dysfunction

Severe liver dysfunction in patients withMycoplasma pneumoniaeinfection

2010 ◽  
Vol 52 (2) ◽  
pp. e105-e107 ◽  
Author(s):  
Akitoshi Murayama ◽  
Daiki Abukawa ◽  
Keiko Watanabe ◽  
Hiroaki Umebayashi ◽  
Tetsuji Inagaki ◽  
...  
Keyword(s):  
Liver Dysfunction ◽  
Severe Liver ◽  
Severe Liver Dysfunction

scholarly journals Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial

2016 ◽  
Vol 76 (5) ◽  
pp. 840-847 ◽  
Author(s):  
Gerd R Burmester ◽  
Yong Lin ◽  
Rahul Patel ◽  
Janet van Adelsberg ◽  
Erin K Mangan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Active Rheumatoid Arthritis ◽  
Activity Index ◽  
Joint Disease ◽  
Phase Iii ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
End Point

ObjectivesTo compare efficacy and safety of sarilumab monotherapy with adalimumab monotherapy in patients with active rheumatoid arthritis (RA) who should not continue treatment with methotrexate (MTX) due to intolerance or inadequate response.MethodsMONARCH was a randomised, active-controlled, double-blind, double-dummy, phase III superiority trial. Patients received sarilumab (200 mg every 2 weeks (q2w)) or adalimumab (40 mg q2w) monotherapy for 24 weeks. The primary end point was change from baseline in 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) at week 24.ResultsSarilumab was superior to adalimumab in the primary end point of change from baseline in DAS28-ESR (−3.28 vs −2.20; p<0.0001). Sarilumab-treated patients achieved significantly higher American College of Rheumatology 20/50/70 response rates (sarilumab: 71.7%/45.7%/23.4%; adalimumab: 58.4%/29.7%/11.9%; all p≤0.0074) and had significantly greater improvement in Health Assessment Questionnaire-Disability Index (p=0.0037). Importantly, at week 24, more patients receiving sarilumab compared with adalimumab achieved Clinical Disease Activity Index remission (7.1% vs 2.7%; nominal p=0.0468) and low disease activity (41.8% vs 24.9%; nominal p=0.0005, supplemental analysis). Adverse events occurred in 63.6% (adalimumab) and 64.1% (sarilumab) of patients, the most common being neutropenia and injection site reactions (sarilumab) and headache and worsening RA (adalimumab). Incidences of infections (sarilumab: 28.8%; adalimumab: 27.7%) and serious infections (1.1%, both groups) were similar, despite neutropenia differences.ConclusionsSarilumab monotherapy demonstrated superiority to adalimumab monotherapy by improving the signs and symptoms and physical functions in patients with RA who were unable to continue MTX treatment. The safety profiles of both therapies were consistent with anticipated class effects.Trial registration numberNCT02332590.

Update on overall survival (OS) of RESCUE: An open-label, phase 2 trial of camrelizumab (C) in combination with apatinib (A) in patients with advanced hepatocellular carcinoma (HCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4076-4076
Author(s):  
Yun Zhang ◽  
Jianming Xu ◽  
Jie Shen ◽  
Shanzhi Gu ◽  
Lihua Wu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Durable Response ◽  
Advanced Hcc ◽  
Phase 2 Trial ◽  
Open Label Phase

4076 Background: C+A combination therapy displayed high objective response rate, disease control rate, and durable response with a manageable safety profile in patients (pts) with advanced HCC. Here we performed an updated analysis of OS to characterize the OS benefit of C+A in HCC pts. Methods: 70 pts in first-line cohort and 120 pts in second-line cohort were enrolled. Median OS and 2-year OS rate were evaluated via updated data (data cutoff, 3 January, 2021). Median time from enrollment to data cutoff of the total population (N = 190) was 29.1 months (range, 24.0-33.7). Results: OS events had occurred in 58.6% pts in first-line cohort and 60.0% pts in second-line cohort. The median OS was 20.1 months (95% CI, 14.9-NR) and 2-year OS rate was 43.3% (95% CI, 31.3-54.7) in first-line cohort. The median OS was 21.8 months (95% CI, 17.3-26.8) and 2-year OS rate was 44.6% (95% CI, 35.5-53.3) in second-line cohort. Conclusions: Long-term follow-up of C+A demonstrated remarkable survival benefit in advanced HCC pts, which further suggested that C+A is a promising combination therapy in advanced HCC pts. Clinical trial information: NCT03463876.

scholarly journals Efficacy and safety of abiraterone acetate plus prednisone in Japanese patients with newly diagnosed, metastatic hormone-naive prostate cancer: final subgroup analysis of LATITUDE, a randomized, double-blind, placebo-controlled, phase 3 study

2020 ◽  
Vol 50 (7) ◽  
pp. 810-820
Author(s):  
Hiroyoshi Suzuki ◽  
Toshitaka Shin ◽  
Satoshi Fukasawa ◽  
Katsuyoshi Hashine ◽  
Sumiko Kitani ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Subgroup Analysis ◽  
Interim Analysis ◽  
Abiraterone Acetate ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Cutoff Date

Abstract Background LATITUDE was a randomized, double-blind, international and phase 3 study of abiraterone acetate plus prednisone in patients with high-risk metastatic hormone-naïve prostate cancer. In the first interim analysis of LATITUDE (clinical cutoff date: 31 October 2016), significant prolongation in overall survival and radiographic progression-free survival (co-primary endpoints) was observed when compared with placebo. The results of the Japanese subgroup analysis of LATITUDE first interim analysis were consistent with those of the overall population. In this study, overall survival and safety results from the final analysis of the Japanese subgroup of the LATITUDE study are presented (clinical cutoff date: 15 August 2018). Methods Abiraterone acetate (1000 mg/day) and prednisone (5 mg/day) were administered orally in the abiraterone acetate plus prednisone group, and matching placebos in the placebo group. Results Of the 1199 patients included in LATITUDE, 70 constituted the Japanese subgroup (abiraterone acetate plus prednisone: n = 35, placebo: n = 35). Following a median (range) follow-up of 56.6 (2.5, 64.2) months, the median overall survival was not reached in both the treatment arms of the Japanese subgroup (hazard ratio: 0.61; 95% confidence interval: 0.27–1.42; nominal P = 0.2502). A total of 23 deaths (abiraterone acetate plus prednisone: 9 [25.7%], placebo group: 14 [40.0%]) were reported in Japanese subgroup. Grade 3/4 adverse events were reported in 24 (68.6%) and 9 (25.7%) patients in the abiraterone acetate plus prednisone and placebo groups, respectively. Conclusions In this Japanese subgroup analysis, addition of abiraterone acetate plus prednisone to androgen-deprivation therapy demonstrated favorable efficacy and safety outcomes in patients with newly diagnosed, high-risk metastatic hormone-naïve prostate cancer. Survival benefits observed in the Japanese subgroup first interim analysis were sustained long-term and were consistent with the overall population.

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