SESOTHO trial (“Switch Either near Suppression Or THOusand”) – switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa

TPS3618 Background: Both anti-EGFR and anti-VEGF therapies have shown clinical benefit when they are added in first and second-line in L-sided CRC. The conflicting results in anti-VEGF vs. anti-EGFR studies (FIRE-3, PEAK and CALGB/SWOG 80405 studies) suggest that the sequence of targeted therapies added to FOLFOX or FOLFIRI regimens in first- and second-line treatment could be an important factor in the overall survival (OS) of mCRC patients. Currently, there are no randomized data on the sequential use of an anti-EGFR followed by an anti-VEGF or vice versa. Therefore, the aim of this randomized clinical trial is to compare the efficacy of two treatment sequences, panitumumab followed by bevacizumab versus bevacizumab followed by panitumumab in combination with FOLFOX chemotherapy in first-line and with FOLFIRI in second-line in patients with wild-type RAS, primary L-sided, metastatic colorectal cancer (mCRC). Methods: A phase III, multicentre, open-label and randomized two-arm clinical trial. Untreated patients with wild-type RAS mCRC (determined locally), primary L-sided and unresectable will be screened for this trial. Eligible patients will be randomized 1:1 to receive first-line (1L) panitumumab plus FOLFOX and then bevacizumab plus FOLFIRI as second-line (2L) treatment (Seq. 1) or bevacizumab plus FOLFOX as 1L and then panitumumab plus FOLFIRI as 2L treatment (Seq. 2). Randomization will be stratified by number of metastatic organs involved (1 vs > 1). Primary objective is the comparison of the progression free survival (PFS) rate at 35 months (m) of Seq 1 vs Seq. 2. Secondary objectives: PFS from randomization to 2nd progression or death, OS rate at 35 months and OS of Seq. 1 vs Seq. 2; PFS, objective response rate, disease control rate, early tumour shrinkage, Depth of Response, duration and time to response and safety in 1L treatment and in 2L treatment in each Sequence arm. Exploratory objectives: impact of baseline biomarkers predictive of the efficacy in each Sequence arm and the clinical impact of clonal dynamics by longitudinal analysis of circulating tumour deoxyribonucleic acid (ctDNA) in plasma. The trial is in progress; 28 of up to 370 planned patients have been recruited at the end of January 2019 (first patient in 31 October 2018). Clinical trial information: NCT03635021.

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1036 A 24-WEEK, PARALLEL-GROUP, OPEN-LABEL, RANDOMIZED CLINICAL TRIAL COMPARING THE EARLY ANTIVIRAL EFFICACY OF TELBIVUDINE AND ENTECAVIR IN THE TREATMENT OF HBEAG-POSITIVE CHRONIC HEPATITIS B

Journal of Hepatology ◽

10.1016/s0168-8278(10)61037-9 ◽

2010 ◽

Vol 52 ◽

pp. S401

Author(s):

M.-H. Zheng ◽

K.-Q. Shi ◽

Z.-J. Dai ◽

C. Ye ◽

Y.-P. Chen

Keyword(s):

Clinical Trial ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Randomized Clinical Trial ◽

Chronic Hepatitis B ◽

Open Label ◽

Antiviral Efficacy ◽

Parallel Group ◽

Positive Chronic Hepatitis

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Surufatinib in combination with toripalimab in patients with advanced neuroendocrine carcinoma: Results from a multicenter, open-label, single-arm, phase II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16199 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16199-e16199

Author(s):

Lin Shen ◽

Xianjun Yu ◽

Ming Lu ◽

Xing Zhang ◽

Ying Cheng ◽

...

Keyword(s):

Clinical Trial ◽

Phase Ii ◽

Neuroendocrine Carcinoma ◽

Kinase Inhibitor ◽

Objective Response ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Open Label ◽

Grade 3

e16199 Background: Patients with advanced neuroendocrine carcinoma (NEC) have a poor prognosis and limited treatment option after first-line treatment. Surufatinib, a multi-kinase inhibitor of VEGFR 1-3, FGFR 1 and CSF-1R, has been approved in patients with advanced or metastatic extra-pancreatic neuroendocrine tumors in China. Toripalimab is a monoclonal humanized IgG4 PD-1 antibody. Surufatinib modulates tumor immune microenvironment and has shown promising antitumor activity in combination with toripalimab in solid tumors, including neuroendocrine tumor and neuroendocrine carcinoma. Herein, we reported the efficacy and safety of surufatinib in combination with toripalimab in a cohort of advanced NEC patients. Methods: The multicenter, open-label, single-arm phase II clinical trial enrolled advanced NEC patients refractory to first-line chemotherapy, and received surufatinib 250 mg once a day orally plus toripalimab 240 mg intravenously on day 1 of a 21-day cycle. The primary end point is objective response rate (ORR) per RECIST 1.1. Results: Twenty-one patients enrolled and received combination therapy. At data cut-off (December 31, 2020), the average treatment cycles were 5.1±3.69 for surufatinib and 5.0±3.68 for toripalimab. Among 20 tumor evaluable patients, 4 patients achieved confirmed PR and 10 patients achieved stable disease. The ORR and disease control rate (DCR) are 20 % (95%CI: 5.7%-43.7%) and 70% (95%CI: 45.7%-88.1%) respectively. The median PFS is 3.94 months (95%CI: 1.31- unknown). OS is not mature till data cut-off. Adverse events (AEs) reported as related to treatment (TRAE) occurred in 100% of patients, of which Grade≥3 TRAEs occurred in 33.3% of patients. The reported Grade≥3 TRAEs were hypertension in 2 (9.5%) patients, and upper abdominal pain, oral mucositis, neutrophil count decreased, leukocyte count decreased, dermatitis, anemia and backache in 1 (4.8%) patient each. Immune related Grade ≥3 AEs, Gamma-glutamyl transpeptidase increased and dermatitis, occurred in 2 (9.5%) patients, respectively. TRAE caused surufatinib or toripalimab interruption occurred in 6 (28.6%) and 4 (19%) patients respectively. There were neither serious AEs nor AEs inducing treatment discontinuations or deaths. Conclusions: As there is no standard second-line treatment, this combination of surufatinib and toripalimab might offer a new promising choice to treat NEC as second-line treatment due to good efficacy and manageable treatment related toxicities. Clinical trial information: NCT04169672.

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A Randomized Clinical Trial of Linagliptin vs. Standard of Care in Patients Hospitalized With Diabetes and COVID-19

Frontiers in Endocrinology ◽

10.3389/fendo.2021.794382 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ran Abuhasira ◽

Irit Ayalon-Dangur ◽

Neta Zaslavsky ◽

Ronit Koren ◽

Mally Keller ◽

...

Keyword(s):

Clinical Trial ◽

Randomized Clinical Trial ◽

Clinical Improvement ◽

Standard Of Care ◽

Ordinal Scale ◽

Care Group ◽

Open Label ◽

Clinical Trial Registration ◽

Point Reduction ◽

Patients With Diabetes

ObjectiveTo assess the effect of linagliptin vs. standard therapy in improving clinical outcomes in patients hospitalized with diabetes and coronavirus disease 2019 (COVID-19).Materials and MethodsWe did an open-label, prospective, multicenter, randomized clinical trial in 3 Israeli hospitals between October 1, 2020, and April 4, 2021. Eligible patients were adults with type 2 diabetes mellitus and a diagnosis of COVID-19. A total of 64 patients, 32 in each group, were randomized to receive linagliptin 5 mg PO daily throughout the hospitalization or standard of care therapy. The primary outcome was time to clinical improvement within 28 days after randomization, defined as a 2-point reduction on an ordinal scale ranging from 0 (discharged without disease) to 8 (death).ResultsThe mean age was 67 ± 14 years, and most patients were male (59.4%). Median time to clinical improvement was 7 days (interquartile range (IQR) 3.5-15) in the linagliptin group compared with 8 days (IQR 3.5–28) in the standard of care group (hazard ratio, 1.22; 95% CI, 0.70–2.15; p = 0.49). In-hospital mortality was 5 (15.6%) and 8 (25.0%) in the linagliptin and standard of care groups, respectively (odds ratio, 0.56; 95% CI, 0.16–1.93). The trial was prematurely terminated due to the control of the COVID-19 outbreak in Israel.ConclusionsIn this randomized clinical trial of hospitalized adult patients with diabetes and COVID-19 who received linagliptin, there was no difference in the time to clinical improvement compared with the standard of care.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT04371978.

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Apartinib in combination with S-1 for the second-line treatment of advanced pancreatic cancer (APC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.tps781 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. TPS781-TPS781

Author(s):

Junjie Hang ◽

Lixia Wu ◽

Ruohan Yin ◽

Muhan Liu ◽

Kequn Xu

Keyword(s):

Pancreatic Cancer ◽

Clinical Trial ◽

Kinase Inhibitor ◽

Case Reports ◽

Advanced Pancreatic Cancer ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Open Label ◽

Angiogenic Therapy

TPS781 Background: The prognosis for patients with advanced pancreatic cancer (APC) is extremely dismal. First-line treatment for APC is gemcitabine/5-FU-based chemotherapy with no standard second-line treatment. Anti-angiogenic therapy combined with chemotherapy have showed its effects in improving the outcomes in a variety of cancers. Apatinib is an oral tyrosine kinase inhibitor that selectively targets VEGFR2. Some preclinical studies and several case reports showed the anti-tumor effect of apatinib in pancreatic cancer, but there is no evidence from clinical trial to confirm it. This study aims to evaluate the efficacy and safety of apartinib in combination with S-1 as the second-line therapy for patients with APC. Methods: In this open-label, single-arm, randomized phase II study, we will recruit 30 patients with pathologically proven advanced pancreatic cancer after the failure of first-line chemotherapy. All patients are aged 18-70 years with ECOG PS 0-2 and will receive apatinib at an initial dose of 500mg/d on a continuous basis, and oral S-1 (60mg/d for BSA < 1.25m2, 80mg/d for 1.25<BSA < 1.5m2, and 100mg for BSA >1.5m2, orally) twice a day on days 1-14 of a 21-day cycle. Primary endpoint is PFS. Secondary endpoints include OS, duration of response, ORR and DCR. The safety of apartinib + S-1 will be evaluated by CTCAE v4.0. Translational research will be performed in blood (before and on-treatment): cytokine panel to explore predictive and prognostic biomarkers. Clinical trial information: NCT03662035.

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Randomized Clinical Trial Comparing Concomitant and Tailored Therapy for Eradication of Helicobacter pylori Infection

Journal of Personalized Medicine ◽

10.3390/jpm11060534 ◽

2021 ◽

Vol 11 (6) ◽

pp. 534

Author(s):

Nikola Perkovic ◽

Antonio Mestrovic ◽

Josko Bozic ◽

Mirela Pavicic Ivelja ◽

Jonatan Vukovic ◽

...

Keyword(s):

Clinical Trial ◽

Randomized Clinical Trial ◽

Primary Objective ◽

First Line ◽

Tailored Therapy ◽

Open Label ◽

Intention To Treat ◽

Clarithromycin Resistance ◽

Reasonable Choice ◽

H Pylori

As high clarithromycin resistance (>20%) in the Split-Dalmatia region of Croatia hinders the treatment of H. pylori infection, the primary objective of this study was to compare concomitant quadruple with the tailored, personalized therapy as first-line eradication treatment of H. pylori. In an open-label, randomized clinical trial, 80 patients with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 gr, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or tailored therapy in accordance with the results of the antimicrobial susceptibility testing. Eradication status was assessed 4 weeks after treatment. Eradication rates were significantly higher in tailored group than in concomitant group both in intention-to-treat (70 vs. 92.5%, p = 0.010) and per-protocol (87.5 vs. 100%, p = 0.030) analysis in the setting of increasing antibiotic resistance (clarithromycin 37.5%, metronidazole 17.5%, dual resistance 10%). Adverse effects were more frequent in the concomitant group (32.5 vs. 7.5%, p = 0.006). Tailored therapy achieves higher eradication with a lower adverse events rate. With the increasing resistance of H. pylori strains to antibiotic treatment, eradication regimes with such characteristics should be strongly considered as a reasonable choice for first-line treatment.

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FOLFIRI (folinic acid, fluorouracil, and irinotecan) increases not efficacy but toxicity compared with single-agent irinotecan as a second-line treatment in metastatic colorectal cancer patients: a randomized clinical trial

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211068737 ◽

2022 ◽

Vol 14 ◽

pp. 175883592110687

Author(s):

Xiaowei Zhang ◽

Ran Duan ◽

Yusheng Wang ◽

Xin Liu ◽

Wen Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Trial ◽

Metastatic Colorectal Cancer ◽

Folinic Acid ◽

Randomized Clinical Trial ◽

Chemotherapy Regimen ◽

Single Agent ◽

Line Treatment ◽

Second Line ◽

First Line

Background: FOLFIRI [irinotecan, folinic acid (CF), and fluorouracil] is considered a standard second-line chemotherapy regimen for patients with metastatic colorectal cancer (mCRC) who failed first-line XELOX/FOLFOX regimens. However, it remains unknown whether fluorouracil is still necessary in this case. This trial was designed to test the superiority of FOLFIRI over single-agent irinotecan as a second-line treatment for patients with mCRC. Methods: This randomized clinical trial was conducted in five hospitals in China. From 4 November 2016 to 17 January 2020, patients aged 18 years or older with histologically confirmed unresectable mCRC and who had failed first-line XELOX/FOLFOX regimens were screened and enrolled. Patients were randomized to receive either FOLFIRI or irinotecan. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and toxicity. Data were analyzed on an intention-to-treat basis. Results: A total of 172 patients with mCRC were randomly treated with FOLFIRI ( n = 88) or irinotecan ( n = 84). The median PFS was 104 and 112 days (3.5 and 3.7 months) in the FOLFIRI and irinotecan groups, respectively [hazard ratio (HR) = 1.084, 95% confidence interval (CI) = 0.7911–1.485; p = 0.6094], and there was also no significant difference in OS and ORR between the two groups. The incidence of the following adverse events (AEs) was significantly higher in the FOLFIRI group than in the irinotecan group: any grade AEs including leucopenia (73.9% versus 55.4%), neutropenia (72.7% versus 56.6%), thrombocytopenia (31.8% versus 18.1%), jaundice (18.2% versus 7.2%), mucositis (40.9% versus 14.5%), vomiting (37.5% versus 21.7%), and fever (19.3% versus 7.2%) and grade 3–4 neutropenia (47.7% versus 21.7%). Conclusion: This is the first head-to-head trial showing that single-agent irinotecan yielded PFS, OS, and ORR similar to FOLFIRI, with a more favorable toxicity profile; therefore, it might be a more favorable standard chemotherapy regimen for mCRC patients who failed first-line XELOX/FOLFOX regimens. Trial registration: This study is registered with ClinicalTrials.gov, number NCT02935764, registered 17 October 2016, https://clinicaltrials.gov/ct2/show/NCT02935764 .

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