scholarly journals Furosemide versus mannitol in patients who received cisplatin-based chemotherapy using short hydration: study protocol for a randomized controlled trial

2018 ◽  
Author(s):  
Eriko Murakami ◽  
Hiroaki Akamatsu ◽  
Toshio Shimokawa ◽  
Kiyoko Wada ◽  
Nobuyuki Yamamoto
Keyword(s):  
Renal Dysfunction ◽  
Phase Ii ◽  
Medical Information ◽  
Controlled Trial ◽  
University Hospital ◽  
Open Label ◽  
Open Label Phase ◽  
Secondary Endpoints ◽  
Clinical Trials Registry ◽  
Thoracic Malignancies

Abstract Background: Cisplatin (CDDP) is a key drug for various thoracic malignancies. To avoid renal toxicity of CDDP, mannitol is routinely used, but it reportedly causes phlebitis. Furosemide is another widely-used option for diuresis, but to date, it has not been assessed in comparison with mannitol. We therefore undertake a randomized phase II comparative study of furosemide and mannitol in CDDP-based chemotherapy using short hydration. Methods: This study is designed as a two-arm, prospective, randomized, single-center, open-label phase II study. The primary endpoint is set as the proportion of patients who experienced any grade renal dysfunction, defined as elevation in creatinine using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, during the first cycle. Secondary endpoints are: the proportion of patients who experienced ≥ grade 2 renal dysfunction during the first cycle, any grade and ≥ grade 2 renal dysfunction after the completion of forth cycle, and the proportion of patients who had phlebitis. A total of 105 patients will be enrolled in this trial. Discussion: The results of this study will suggest that furosemide can be better choice than mannitol regarding convenience and in reduction of phlebitis. Trial registration: University Hospital Medical Information Network Clinical Trials Registry, ID: UMIN000031910(http://www.umin.ac.jp/ctr/index.htm). Registered on 1 April 2018.

scholarly journals Furosemide versus mannitol in Japanese patients with thoracic malignancy who received cisplatin-based chemotherapy using short hydration: study protocol for a randomised controlled trial

BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e029057
Author(s):  
Eriko Murakami ◽  
Hiroaki Akamatsu ◽  
Toshio Shimokawa ◽  
Kiyoko Wada ◽  
Nobuyuki Yamamoto
Keyword(s):  
Phase Ii ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Japanese Patients ◽  
Open Label ◽  
Institutional Review ◽  
Open Label Phase ◽  
Registration Number ◽  
Randomised Controlled ◽  
Thoracic Malignancies

IntroductionCisplatin (CDDP) is a key drug for various thoracic malignancies. To avoid renal toxicity of CDDP, mannitol is routinely used, but it sometimes causes phlebitis which damages patients’ quality of life. Furosemide is another widely used option for diuresis administered more quickly. To date, previous comparisons of these diuretics have lacked statistical significance owing to study design. We therefore undertake a randomised phase II comparative study of furosemide and mannitol in CDDP-based chemotherapy using short hydration.Methods and analysisThis is a two-arm, prospective, randomised, single-centre, open-label phase II study. The primary endpoint is set as the proportion of patients who experienced any grade of ‘creatinine increase’ using the Common Terminology Criteria for Adverse Events V.4.0, during the first cycle. Secondary endpoints are: the proportion of patients who experienced ≥grade 2 of creatinine increase during the first cycle, any grade and ≥grade 2 of creatinine increase after the completion of fourth cycle, and the proportion of patients with phlebitis. Enrolled in this trial will be 105 patients.Ethics and disseminationThis study was approved by the Wakayama Medical University Institutional Review Board on 30 March 2018 study (approval number: 2258). Patients have been enrolled since May 2018. As the study will complete accrual in March 2021, results will be published by 2021. This study will provide important information about the utility of furosemide compared with mannitol to protect against nephrotoxicity.Trial registration numberUMIN000031910.

scholarly journals An open-label, randomized controlled trial of sulfamethoxazole–trimethoprim for Pneumocystis prophylaxis: results of 52-week follow-up

2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Masako Utsunomiya ◽  
Hiroaki Dobashi ◽  
Toshio Odani ◽  
Kazuyoshi Saito ◽  
Naoto Yokogawa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Medical Information ◽  
Controlled Trial ◽  
Pneumocystis Pneumonia ◽  
University Hospital ◽  
Discontinuation Rate ◽  
Open Label ◽  
Strength Group ◽  
Drug Retention ◽  
Clinical Trials Registry

Abstract Objectives The aim was to investigate the long-term prophylactic efficacy, drug retention and safety of low-dose sulfamethoxazole–trimethoprim (SMX/TMP) prophylaxis against Pneumocystis pneumonia (PCP). Methods Adult patients with rheumatic diseases receiving prednisolone ≥0.6 mg/kg/day were randomized into the single-strength group (SS; SMX/TMP 400/80 mg daily), the half-strength group (HS; 200/40 mg daily) or the escalation group (ES; starting at 40/8 mg and increasing incrementally to 200/40 mg daily) and treated for 24 weeks, then observed for 52 weeks. The primary endpoint, the PCP non-incidence rate (non-IR) at week 24, has been reported previously. The secondary endpoints were the PCP non-IR at week 52, treatment discontinuation rate and adverse events. Results Fifty-eight, 59 and 55 patients in the SS, HS and ES, respectively, received SMX/TMP. PCP did not develop in any of the patients by week 52. The estimated PCP non-IR in patients receiving SMX/TMP 200/40 mg daily (HS and ES) was 96.8–100%. Throughout the 52-week observation period, the overall discontinuation rate was significantly lower in HS than in SS (22.7 vs 47.2%, P = 0.004). The discontinuation rates attributable to adverse events were significantly lower in HS (19.1%, P = 0.007) and ES (20.3%, P = 0.007) than in SS (41.8%). The IRs of adverse events requiring SMX/TMP dose reduction before week 52 differed among the three groups, with a significantly higher IR in SS than in HS or ES (P = 0.007). Conclusion SMX/TMP 200/40 mg had a high PCP prevention rate and was superior to SMX/TMP 400/80 mg in terms of drug retention and safety. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000007727.

Randomized, open-label, phase II study comparing five-weekly S-1 plus cisplatin (SP) with tri-weekly capecitabine plus cisplatin (XP) in chemotherapy-naïve patients with HER2 negative advanced gastric cancer (AGC): OGSG 1105 HERBIS-4A trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 102-102
Author(s):  
Atsushi Takeno ◽  
Youichi Makari ◽  
Shunji Endo ◽  
Jin Matsuyama ◽  
Ryohei Kawabata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Open Label ◽  
Group 13 ◽  
Common Grade ◽  
Open Label Phase ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
To Receive

102 Background: This phase II study aimed to investigate the safety and efficacy of XP compared to SP in the first-line treatment of HER2 negative AGC. Methods: Patients were randomly assigned to receive either SP (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/ m2 on day 8, every 5 weeks) or XP (capecitabine 1,000 mg/m2 twice daily for 14 days plus cisplatin 80 mg/m2 on day 1, every 3 weeks). Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), and adverse events. Results: 84 eligible patients were randomly assigned to receive SP ( N = 41) or XP ( N = 43). No statistical difference was observed in overall RR between the SP and XP groups [51.2% (95% CI, 35.1% to 67.1%) vs. 53.5% (95% CI, 37.7% to 68.8%), P = 1.000]. Despite not significant, however, SP vs. XP showed a trend toward better PFS [median, 5.9 months vs. 4.1 months; hazard ratio (HR), 0.763; 95% CI, 0.462 to 1.259; P = .284] and OS (median, 13.5 months vs. 10.0 months; HR, 0.776; 95% CI, 0.485 to 1.244; P = .290). This trend in the SP vs. XP comparison was more pronounced in TTF (median, 4.5 months vs. 3.1 months; HR, 0.651; 95% CI, 0.421 to 1.006; P = .052). Common grade 3 to 4 hematological toxicities were neutropenia and anemia (SP group, 23% and 23%; XP group, 35% and 28%). Grade 3-4 anorexia and hyponatremia were more frequently seen in the XP group (31% and 16%) compared to the SP group (13% and 5%). Treatment-related deaths occurred in one patient (2.3%) in the XP group. Conclusions: XP failed to demonstrate the superior efficacy over SP. Higher incidence of severe toxicities by XP suggests SP as the standard 1st line chemotherapy for HER2 negative AGC in Japan. Clinical trial information: UMIN000006755.

scholarly journals Pimasertib Versus Dacarbazine in Patients With Unresectable NRAS-Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1727 ◽  
Author(s):  
Celeste Lebbé ◽  
Caroline Dutriaux ◽  
Thierry Lesimple ◽  
Willem Kruit ◽  
Joseph Kerger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cutaneous Melanoma ◽  
Controlled Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Serious Adverse Events ◽  
Unresectable Stage ◽  
Secondary Endpoints ◽  
Grade 3

This study investigated the efficacy and safety of pimasertib (MEK1/MEK2 inhibitor) versus dacarbazine (DTIC) in patients with untreated NRAS-mutated melanoma. Phase II, multicenter, open-label trial. Patients with unresectable, stage IIIc/IVM1 NRAS-mutated cutaneous melanoma were randomized 2:1 to pimasertib (60 mg; oral twice-daily) or DTIC (1000 mg/m2; intravenously) on Day 1 of each 21-day cycle. Patients progressing on DTIC could crossover to pimasertib. Primary endpoint: investigator-assessed progression-free survival (PFS); secondary endpoints: overall survival (OS), objective response rate (ORR), quality of life (QoL), and safety. Overall, 194 patients were randomized (pimasertib n = 130, DTIC n = 64), and 191 received treatment (pimasertib n = 130, DTIC n = 61). PFS was significantly improved with pimasertib versus DTIC (median 13 versus 7 weeks, respectively; hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.42–0.83; p = 0.0022). ORR was improved with pimasertib (odds ratio 2.24, 95% CI 1.00–4.98; p = 0.0453). OS was similar between treatments (median 9 versus 11 months, respectively; HR 0.89, 95% CI 0.61–1.30); 64% of patients receiving DTIC crossed over to pimasertib. Serious adverse events (AEs) were more frequent for pimasertib (57%) than DTIC (20%). The most common treatment-emergent AEs were diarrhea (82%) and blood creatine phosphokinase (CPK) increase (68%) for pimasertib, and nausea (41%) and fatigue (38%) for DTIC. Most frequent grade ≥3 AEs were CPK increase (34%) for pimasertib and neutropenia (15%) for DTIC. Mean QoL scores (baseline and last assessment) were similar between treatments. Pimasertib has activity in NRAS-mutated cutaneous melanoma and a safety profile consistent with known toxicities of MEK inhibitors. Trial registration: ClinicalTrials.gov, NCT01693068.

Phase II trial of panobinostat (LBH589) in patients (pts) with refractory metastatic colorectal cancer (MCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 582-582 ◽  
Author(s):  
Philip Jordan Gold ◽  
David A. Smith ◽  
Desiree Iriarte ◽  
Barry Boatman ◽  
Henry G. Kaplan
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Open Label ◽  
Ecog Performance Status ◽  
Treatment Regimes ◽  
Open Label Phase ◽  
Secondary Endpoints

582 Background: LBH589 is a novel histone deacetylase inhibitor (HDACi) which induces apoptosis of tumor cells. LBH589 has been shown to cause regression of colon cancer in animal models and phase I trials have shown the agent to be well tolerated, providing rationale for studying this agent in pts with MCRC. Methods: This was a multicenter, open-label phase II study of single agent LBH589 in patients with MCRC who failed at least 2 prior regimens for metastatic disease. Measurable disease, adequate organ function and ECOG performance status of 0-2 were required. Pts received LBH589 30mg po on M/W/F until disease progression. Pts were evaluated for toxicity every 2 weeks and for response every 8 weeks. The primary endpoint was overall survival. Secondary endpoints included response rate, time to progression (TTP), and toxicity. Results: 29 pts were enrolled (16 male, 13 female). The median age was 59 (range 41-76). The median number of prior treatment regimes was 3 (2-11). The median survival was 5.1 months (range 1-24+). There were no objective responses. 3 pts had SD at 8 weeks. The median TTP was 7.7 weeks (range 1-38.). Six pts had grade 4 thrombocytopenia requiring platelet transfusion. Nine pts required dose reductions for toxicity. Conclusions: Single-agent LBH589 was not associated with objective tumor responses in this heavily pre-treated pt population. However, the median survival was comparable to that seen in other trials of single agent targeted therapy in the treatment of refractory MCRC. Thrombocytopenia was significant, and may complicate potential trials of combination therapy.

Videoconference-Based Cognitive Behavioral Therapy in Symptomatic Panic Disorder Following Primary Pharmacotherapy: Randomized, Assessor-Blinded, Controlled Trial (Preprint)

2021 ◽  
Author(s):  
Yoichi Seki ◽  
Ryo Takemura ◽  
Chihiro Sutoh ◽  
Remi Noguchi ◽  
Yoko Okamoto ◽  
...  
Keyword(s):  
Panic Disorder ◽  
Cognitive Behavioral Therapy ◽  
Medical Information ◽  
Behavioral Therapy ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Cognitive Behavioral ◽  
University Hospital ◽  
Open Label ◽  
Post Intervention

BACKGROUND Background: Given the difficulty in accessing cognitive behavioral therapy, pharmacotherapy remains the standard of care for panic disorder (PD). OBJECTIVE Objectives: This study aimed to determine the effectiveness of videoconference-based cognitive behavioral therapy (VCBT) for patients who remain symptomatic after primary pharmacotherapy as an adjunct to usual care (UC) when compared with UC alone. METHODS Methods: This prospective, randomized, open-label endpoint trial enrolled 30 patients with PD who did not respond to primary pharmacotherapy, including antidepressants and anxiolytics, after ≥8 weeks of therapy, who underwent VCBT (n=15) or UC (n=15) between November 2017 and March 2020 at Chiba University Hospital in Chiba, Japan. They were evaluated at screening, week 0 (baseline), week 8 (mid-intervention), and week 16 (post-intervention). The primary outcome was the change in the PD Severity Scale (PDSS) score at week 16 from baseline. RESULTS Results: After 16 weeks, the adjusted mean changes in the PDSS score from baseline were −7.92 and 0.75 in the VCBT and UC groups, respectively, with a between-group difference of −8.67 (95% CI: −11.80 to −5.54, P<.0001). A higher proportion of patients in the VCBT group responded to treatment (≥40% reduction in the PDSS score at week 16) and experienced remission (PDSS score <8 points at week 8) than those in the UC group (P<.0001). CONCLUSIONS Conclusions: Our results suggest that VCBT is an effective treatment adjunct to UC in patients with PD who remain symptomatic following primary pharmacotherapy and improves PD symptoms in these patients. CLINICALTRIAL Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000029987; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000034247.

Randomized phase II study of nivolumab (N) alone versus with pegilodecakin (PEG) in combination with N in patients (pts) with post-platinum immunotherapy-naive stage IV non-small cell lung cancer (NSCLC) and no or low PD-L1 expression (CYPRESS 2).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21744-e21744
Author(s):  
Robert M. Jotte ◽  
Jerome H. Goldschmidt ◽  
Jeffrey Gary Schneider ◽  
Merrill Kingman Shum ◽  
David Berz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Smoking History ◽  
Prior History ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Open Label Phase ◽  
History Of ◽  
Secondary Endpoints

e21744 Background: Nivolumab (N) is an immune checkpoint inhibitor (CPI) approved to treat post-platinum NSCLC as monotherapy. PEG in combination with N has demonstrated promising efficacy in NSCLC pts in a phase I trial (IVY; NCT02009449; Naing et al., 2019 Lancet Oncol), providing rationale for this randomized phase II trial (CYPRESS 2). Methods: CYPRESS 2 was an open label phase II trial, for ECOG 0-1, PD-L1 negative or low (TPS 0-49%), Stage IV NSCLC pts, without known EGFR/ALK mutations. Pts were randomized 1:1 to arm N (240 mg every 14-days or 480 mg every 28-days as decided by investigator) v. arm PEG+N (received N as above + PEG daily of 0.8 mg if weight ≤80kg and 1.6mg if weight > 80 kg). Pts were stratified by tumor histology and smoking history and must have no prior history of cancer or CPI therapy. Primary endpoint was ORR (per RECIST v 1.1 per investigator). Secondary endpoints included PFS, OS, and safety. Exploratory endpoints included immune activation biomarkers (baseline and change from baseline), assessed by immunoassay. Results: As of Aug 28, 2019, 52 pts were randomized to PEG+N (n=27) or N (n=25). Median follow-up time was 11.6 months. The following results were found for PEG+N versus N: ORR 14.8% v. 12.0%, mPFS 1.9 v. 1.9 months with HR = 1.01 (95% CI [0.52, 1.95]), mOS 6.7 v. 10.7 months with HR = 1.87 (95% CI [0.77, 4.53]). Gr ≥3 treatment related adverse events (TRAEs) for PEG+N versus N were 70.4% vs. 16.7%. Gr 3 TRAEs of ≥10% incidence included anemia (40.7% v. 0%), fatigue (18.5% v. 0%), and thrombocytopenia (14.8% v. 0%). In PEG+N arm, increased circulating IL-18, Granzyme B, FasL, and IFNg levels and decreased TGFb levels were observed on treatment. Conclusions: Exploratory pharmacodynamic results were consistent with immunostimulatory signals of the IL-10R pathway. Despite evidence of biological effect, adding PEG to N did not lead to improvement in ORR, PFS, or OS in post-platinum advanced NSCLC with no or low PD-L1 expression. PEG+N arm demonstrated expected safety profile but overall higher toxicity compared to nivolumab alone. Clinical trial information: NCT03382912.

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