scholarly journals A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Claire Morice ◽  
Dewleen G. Baker ◽  
Marguerite M. Patel ◽  
Tracy L. Nolen ◽  
Kayla Nowak ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Adverse Events ◽  
Glucocorticoid Receptor ◽  
Healthy Volunteers ◽  
Pilot Trial ◽  
Pharmacokinetic Interaction ◽  
Random Order ◽  
Primary Objective ◽  
Serious Adverse Events ◽  
Pharmacodynamic Interactions

AbstractPT150, a novel competitive glucocorticoid receptor (GR) antagonist, has proven safe in animal models, healthy volunteers, and people with depression. Our study is the first to investigate PT150’s safety with alcohol use. The primary objective of this study was to evaluate pharmacodynamic interactions between ethanol and PT150 in healthy subjects. This single-site, Phase I pilot trial consisted of community-recruited, healthy, alcohol-experienced participants aged 21–64 years. Of 32 participants screened, 11 were enrolled and randomized, one of which withdrew before intervention. PT150 (900 mg/day) was administered orally to all participants for five days. All participants received two beverage challenges on Day 1 (before PT150 administration) and Day 5 (after PT150 administration). On challenge days, they received both alcohol (16% ethanol) and placebo (1% ethanol) beverages in random order. Primary outcomes included breath alcohol level, blood pressure, heart rate, adverse events, and electrocardiogram changes. There were no statistically significant differences in vital signs or estimated blood alcohol concentrations between PT150 non-exposed and exposed groups during the ethanol challenge. There were no clinically significant abnormal electrocardiograms or serious adverse events. These data show that administration of PT150 with concurrent alcohol use is safe and well-tolerated. This study supports a future pharmacokinetic interaction study between PT150 and alcohol.Trial Registration ClinicalTrials.gov Identifier: NCT03548714.

scholarly journals 1288. Phase 1 First-in-Human Single- and Multiple-Ascending Dose Trial Demonstrates Pharmacokinetics (PK) and Tolerability of SPR720, an Oral DNA GyrB Inhibitor for Mycobacterial Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S659-S659
Author(s):  
Angela Talley ◽  
Archie Thurston ◽  
Grayson Moore ◽  
Myriah M Satterfield ◽  
Erika L Manyak ◽  
...  
Keyword(s):  
Adverse Events ◽  
Healthy Volunteers ◽  
Controlled Trial ◽  
Phase 1 ◽  
Safety Data ◽  
Elderly Subjects ◽  
Independent Contractor ◽  
Serious Adverse Events ◽  
Healthy Elderly ◽  
Dose Proportional

Abstract Background SPR720 (phosphate pro-drug of SPR719) is a novel aminobenzimidazole bacterial DNA gyrase (GyrB) inhibitor in development for non-tuberculous mycobacterial lung disease (NTM-LD) and pulmonary tuberculosis. SPR719 has broad-spectrum activity versus clinically relevant mycobacteria in vitro and in murine and hollow fiber (HF) infection models. In this first-in-human single ascending dose (SAD) /multiple ascending dose (MAD) study, the safety, tolerability and pharmacokinetics (PK) of SPR720/SPR719 were evaluated in healthy volunteers. Methods This was a Phase 1 randomized, double-blind, placebo-controlled trial with 7 SAD cohorts (including a food effect cohort) and 5 MAD cohorts. Healthy volunteers (n=8/cohort, 3:1 randomization) received SPR720 or placebo in single oral doses of ranging from 100 mg to 2000 mg or repeat total daily doses ranging from 500 mg to 1500 mg for 7 or 14 days. Safety monitoring and PK sampling occurred throughout the trial. Plasma and urine concentrations of SPR720/SPR719 were measured by validated LC-MS/MS methods. PK parameters were calculated using non-compartmental analysis. Results A total of 96 subjects (including 8 healthy elderly subjects, age ≥ 65 years) were randomized and received study drug. SPR720 was well-tolerated at daily doses up to 1000 mg for up to 14 days. Across SAD/MAD cohorts, the most common adverse events were gastrointestinal (nausea, vomiting and diarrhea) and headache, all of mild or moderate severity and dose dependent. No serious adverse events were reported. Across SAD cohorts, a dose proportional and greater-than-dose proportional increase in SPR719 plasma Cmax and AUC0-24, respectively were observed. SPR720 was rapidly absorbed with a mean SPR719 t1/2 of 2.9-4.5 h. Dosing with food decreased SPR719 plasma AUC by ~20%. No clinically meaningful effect of age on plasma AUC was observed. In the MAD cohorts, SPR719 plasma exposure declined approximately 40% between Day 1 and Day 7, suggesting induction of an elimination pathway. However, plasma AUC0-24 was similar at Days 7 and 14. Conclusion Together with HF pharmacodynamic data, human PK and safety data for SPR720 suggest that predicted therapeutic exposures can be attained with a well-tolerated once-daily dose. Further evaluation in a Phase 2 NTM-LD trial is planned. Disclosures Angela Talley, MD, Spero Therapeutics (Employee, Shareholder) Archie Thurston, Jr., PhD, Spero Therapeutics (Consultant) Grayson Moore, BA, RN, Spero Therapeutics, Inc. (Shareholder, Independent Contractor) Vipul Kumar, PhD, Spero Therapeutics (Employee, Shareholder) Suzanne Stokes, PhD, Spero Therapeutics (Employee, Shareholder) Aaron Dane, MSc, Spero theraputics (Consultant) David Melnick, MD, Spero Therapeutics (Employee)Spero Therapeutics (Employee)

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

2021 ◽  
Vol 32 (4) ◽  
pp. 972-982 ◽  
Author(s):  
Francesco Scolari ◽  
Elisa Delbarba ◽  
Domenico Santoro ◽  
Loreto Gesualdo ◽  
Antonello Pani ◽  
...  
Keyword(s):  
Complete Remission ◽  
Adverse Events ◽  
Membranous Nephropathy ◽  
Partial Remission ◽  
Pilot Trial ◽  
Clinical Trial Registry ◽  
Serious Adverse Events ◽  
First Line Therapy ◽  
Registration Number ◽  
Favorable Safety

BackgroundA cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking.MethodsWe randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g/d to rituximab (1 g) on days 1 and 15, or a 6-month cyclic regimen with corticosteroids alternated with cyclophosphamide every other month. The primary outcome was complete remission of proteinuria at 12 months. Other outcomes included determination of complete or partial remission at 24 months and occurrence of adverse events.ResultsAt 12 months, six of 37 patients (16%) randomized to rituximab and 12 of 37 patients (32%) randomized to the cyclic regimen experienced complete remission (odds ratio [OR], 0.4; 95% CI, 0.13 to 1.23); 23 of 37 (62%) receiving rituximab and 27 of 37 (73%) receiving the cyclic regimen had complete or partial remission (OR, 0.61; 95% CI, 0.23 to 1.63). At 24 months, the probabilities of complete and of complete or partial remission with rituximab were 0.42 (95% CI, 0.26 to 0.62) and 0.83 (95% CI, 0.65 to 0.95), respectively, and 0.43 (95% CI, 0.28 to 0.61) and 0.82 (95% CI, 0.68 to 0.93), respectively, with the cyclic regimen. Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving the cyclic regimen.ConclusionsThis pilot trial found no signal of more benefit or less harm associated with rituximab versus a cyclic corticosteroid-cyclophosphamide regimen in the treatment of membranous nephropathy. A head-to-head, pragmatic comparison of the cyclic regimen versus rituximab may require a global noninferiority trial.Clinical Trial registry name and registration number:Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO),NCT03018535

scholarly journals A phase I study of a dual PI3-Kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia

2020 ◽  
Author(s):  
Fabian Lang ◽  
Lydia Wunderle ◽  
Susanne Badura ◽  
Eberhard Schleyer ◽  
Monika Brüggemann ◽  
...  
Keyword(s):  
Adverse Events ◽  
Acute Leukemia ◽  
Phase I ◽  
Mtor Inhibitor ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Prolonged Treatment ◽  
Small Subset ◽  
Serious Adverse Events ◽  
Efficient Treatment

Abstract Background Combined inhibition of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) complexes may be an efficient treatment for acute leukemia. The primary objective of this phase I single centre open lable study was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the dual pan-class I PI3K and mTOR inhibitor BEZ235 in patients with advanced leukemia.Methods Herein patients > 18 years of age who had relapsed or showed refractory leukemia were treated with BEZ235 (orally at 300-400 mg BID (cohort -1/1)) to assess safety, tolerability, preliminary efficacy and pharmakokinetic (PK). Adverse events data and serious adverse events were analyzed and haematological and clinical biochemistry toxicities were assessed from laboratory test parameters. Response was assessed for the first time at the end of cycle 1 (day 29) and after every subsequent cycle. Pharmacokinetic and pharmacodynamic analyses of BEZ235 were also included (BEZ235 plasma levels, phosphorylation of AKT, S6 and 4EBP1). On statistics this trial is a multiple ascending dose study in which a following variant of the 3+3 rule (“Rolling Six”), a minimum of 6 and a maximum of 12 patients was recruited for the dose escalation and another 5 were planned for the expansion phase. Results Twenty-four patients with ALL (n=11) or AML (n=12) or CML-BP (n=1) were enrolled. All patients had failed one (n=5) or more lines of therapy (n=5) and 14 patients were in refractory / refractory relapse. No formal MTD was defined, stomatitis and gastrointestinal toxicity at 400 mg BID dose was considered incompatible with prolonged treatment. The RP2D of BEZ235 was defined as 300 mg BID. Four of 24 patients showed clinical benefit. Twenty-two of 24 patients discontinued because of progression, (median time to progression 27 days (4d-112d). There was no association between PK parameters and efficacy or tolerability. Conclusions Combined inhibition of PI3K and mTOR inhibits a clinically meaningful driver pathway in a small subset of patients with ALL, with no benefit in patients with AML. Trial registration ClinicalTrials.gov, identifier NCT01756118. registered 19th Decembre 2012, https://clinicaltrials.gov/ct2/show/NCT01756118

scholarly journals P420 A randomised, observer-blinded phase Ib multiple, ascending dose study of UTTR1147A, an IL-22Fc fusion protein, in healthy volunteers and ulcerative colitis patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S382-S383 ◽  
Author(s):  
F Wagner ◽  
J Mansfield ◽  
C Geier ◽  
A Dash ◽  
Y Wang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fusion Protein ◽  
Healthy Volunteers ◽  
Drug Clearance ◽  
Multiple Time ◽  
Dry Skin ◽  
Serious Adverse Events ◽  
Mucin Production ◽  
Interleukin 22 ◽  
Skin Erythema

Abstract Background Inflammatory bowel disease (IBD) is characterised by gut dysbiosis, weakened epithelial barrier, and a dysregulated immune system. Interleukin-22 (IL-22), an IL-10 family cytokine, has demonstrated efficacy in animal IBD models by promoting intestinal epithelial repair, increasing antimicrobial peptide production, and increasing mucin production via goblet cells1. UTTR1147A is a fusion protein in which IL-22 is linked with the Fc portion of IgG4 to improve the pharmacokinetic (PK) characteristics. Methods A phase I study (NCT02749630) was conducted to evaluate the safety, tolerability, PK, and pharmacodynamics (PD) of repeat IV dosing of UTTR1147A in healthy volunteers (HV) and UC patients with centrally read Mayo endoscopic score ≥ 2. 38 HVs and 24 UC patients were given UTTR1147A or placebo at doses ranging from 30 to 90 µg/kg either biweekly or monthly (6:2 UTTR1147A: placebo per cohort). PK and serum PD (REG3A and CRP) were studied across multiple time points and the Mayo Clinic Score was evaluated at baseline, day 30 and day 85. Results Overall, UTTR1147A was safe and adequately tolerated in HV and UC patients. The most common adverse events were on-target dermatological effects (dry skin, erythema, and pruritus) that were manageable, monitorable and reversible. Dose-limiting non-serious dermatological toxicities (severe dry skin, erythema, exfoliation, and discomfort) were seen in two HVs and 1 UC patient dosed with 90ug/kg Q2wk. There were 2 unrelated serious adverse events (ankle fracture and cytomegalovirus infection) that eventually resolved. PK analyses showed that UTTR1147A exposures were, in general, dose proportional within HVs and within UC patients, with a mean elimination half-life of ~16 days and ~12 days, respectively. At the same dose level, UC patients showed relatively lower drug exposures than HVs, possibly due to faster drug clearance. Consistent with the Phase Ia2, UTTR1147A directly induced production of serum PD biomarkers REG3A and CRP at all dose cohorts tested compared with placebo. Notably, UC patients appear to have attenuated serum PD responses compared with HV. Clinical response was observed in 7/18 patients, and clinical remission in 5/18 patients treated with UTTR1147A compared with 1/6 and 0/6 placebo patients, respectively. Conclusion UTTR1147A demonstrated adequate safety and PK profile in healthy volunteers and UC patients. PD biomarker data demonstrated pharmacological activity of UTTR1147A providing evidence of IL-22R pathway activation. Together with the preliminary signals of efficacy, these data support further investigation of this potential, novel non-immunosuppressive therapy in IBD.

First-in-human dose escalation study of LY2875358 (LY), a bivalent MET antibody, as monotherapy and in combination with erlotinib (E) in patients with advanced cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8093-8093 ◽  
Author(s):  
Jonathan Wade Goldman ◽  
Lee S. Rosen ◽  
Alain Patrick Algazi ◽  
Patricia Kellie Turner ◽  
Volker Wacheck ◽  
...  
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Advanced Nsclc ◽  
Single Agent ◽  
Primary Objective ◽  
Advanced Solid Tumors ◽  
Serious Adverse Events ◽  
Dose Escalation Study ◽  
Human Dose ◽  
Recommended Phase Ii Dose

8093 Background: Activation of the hepatocyte growth factor (HGF)/MET receptor pathway promotes tumor growth, invasion and dissemination. LY is a humanized IgG4 monoclonal bivalent antibody against MET which inhibits ligand dependent- and ligand independent activation of MET. Based on preclinical results, we examined LY alone in patients with advanced solid tumors and LY+E in advanced NSCLC patients. Methods: LY monotherapy was administered 20-2,000 mg Q2W IV to 23 patients with advanced solid tumors. Combination therapy with 700-2,000 mg Q2W IV of LY and E (150 mg QD) was completed in 14 patients with advanced NSCLC. The primary objective was to determine a recommended phase II dose (RPTD) for LY and LY+E. Secondary objectives included assessment of toxicity, PK, PD (including MET extracelluar domain and HGF), and antitumor activity. Results: LY and LY+E were well tolerated. No dose-limiting toxicities, serious adverse events, or ≥ Grade 3 adverse events (AEs) possibly related to LY have been observed. The most frequent (≥5% of patients) AEs possibly related to LY2875358 monotherapy were nausea (8.7 %), vomiting (8.7%), and diarrhea (8.7%). The most frequent (≥10% of patient) grade 1 or 2 adverse event possibly related to LY2875358 in patients treated with LY+E were fatigue (21.4%) and anorexia (14.3%). Durable PR according to RECIST were observed for LY (n=1) and LY+E (n=2 out of 13 evaluable patients; both PR patients positive for MET protein expression). Conclusions: LY appears to be safe when administered as single agent and in combination with E up to 2,000 mg Q2W IV. The RPTD of LY is 750 mg Q2W IV for monotherapy and in combination with E based on PK/PD data. Clinical trial information: NTC 01287546.

A phase I/Ib study of crenolanib with ramucirumab (RAM)/paclitaxel (PTX) as second-line therapy (2L tx) for advanced esophagogastric adenocarcinoma (EGA).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 116-116
Author(s):  
Megan Greally ◽  
Sujata Jha ◽  
Sam S. Yoon ◽  
Jia Li ◽  
Avni Mukund Desai ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Objective Response ◽  
Study Drug ◽  
Standard Of Care ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Serious Adverse Events ◽  
Ecog Ps ◽  
Higher Doses

116 Background: PTX/RAM as 2L tx for patients (pts) with EGA is a standard-of-care based on the RAINBOW trial (Lancet Oncol 2014;15:1224). However, benefit is modest. Upregulation of the platelet-derived growth factor (PDGF)/PDGF receptor-β (PDGFR-β) pathway causes resistance to VEGF inhibition. Crenolanib is a selective inhibitor of PDGFR-β. We report initial results of the dose escalation phase of a study of crenolanib plus RAM/PTX in pts with previously treated advanced EGA. Methods: This phase I/Ib study is enrolling ECOG PS 0-1 EGA pts with progression on first-line chemo. PTX 80 mg/m2/ day on day 1, 8, 15 and RAM 8mg/kg q 14 days were administered with escalating doses of crenolanib (60, 80, 100 mg BID) after a 7 day “run-in” of crenolanib to assess crenolanib-related toxicities. The primary objective was to determine the maximum tolerated dose (MTD) of crenolanib plus RAM/PTX. Safety and preliminary efficacy were examined. Results: 15 pts were treated; 12 male, median age 58 (32-73), 66% were ECOG PS 1. Primary site was gastric in nine pts, GEJ in 4 pts and esophageal in two pts. Three pts each received crenolanib 60mg BID and 80mg BID, six pts received 100mg BID and three pts received higher doses. At data cutoff, eight pts continued on treatment. 12 pts have completed the DLT evaluation period across 3 dose levels (60 to 100 mg BID). Median treatment duration was 76 days (35-191). The combination was well tolerated, with no DLTs or serious adverse events (SAEs) attributed to study drug. Treatment related adverse events occurred in two pts (17%), all grade 1. These were fatigue, nausea, vomiting and hypertension. Disease progression was the most common reason for treatment discontinuation; no pt discontinued due to study drug related AEs. Nine pts were evaluable for response. One pt had objective response; the disease control rate was 78%. Median PFS and OS were 4.1 and 11.9 months respectively. Conclusions: Crenolanib plus RAM/PTX appears well tolerated at a dose level of 100mg BID. Further evaluation is needed to determine efficacy. Accrual is ongoing at higher doses. Once the MTD is defined, the dose expansion phase will enroll 25 pts. Updated data with pharmacokinetics and biomarkers will be presented. Clinical trial information: NCT03193918.

Inhibition of Interleukin-6 (IL-6) Reverses Anemia In Patients with Advanced Non Small Cell Lung Cancer (NSCLC): Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 640-640 ◽  
Author(s):  
Michael W. Schuster ◽  
James R Rigas ◽  
Sergey V Orlov ◽  
Branislav Milovanovic ◽  
Kumar Prabhash ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Chemistry ◽  
Controlled Trial ◽  
Safety Data ◽  
Primary Objective ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Reactive Protein ◽  
Grade 3 ◽  
Cancer Related Anemia

Abstract Abstract 640 Background: ALD518 is a humanized, desialyated anti-IL-6 antibody being developed for the treatment of cancer-related anemia, cachexia and fatigue. The primary objective of the study was to determine the efficacy and safety of ALD518 in patients with advanced NSCLC. Secondary objectives examined hematologic parameters. Methods: 124 patients with NSCLC, ECOG 0–3, weight loss in the preceding 3 months of >5% body weight, hemoglobin (Hb) >7g/dL, and C-reactive protein (CRP) >10mg/L were dosed. Patients were randomized to 1 of 4 groups (n~30/group). Placebo or ALD518 80mg, 160mg, or 320mg was administered intravenously every 8 weeks. Pts were followed up for 24 weeks. Data included hematologic parameters, clinical chemistry, CRP, D-dimer, lean body mass and adverse events (AEs). Quality of life data included the FACIT-F, FACT-L, and FAACT questionnaires. Data presented in this abstract relates to the safety and hematology results. Results: 29 pts completed the study treatments and evaluations, 38 failed to complete every visit, 52 died of progressive disease, and 5 withdrew because of adverse events. There were no dose limiting toxicities (DLTs), infusion reactions, or anti-idiotypic antibody responses to ALD518 observed in the study. 84 pts had serious AEs of which 1 was deemed to be possibly related to administration of ALD518 (rectal hemorrhage). The majority of the serious adverse events were due to progression of the NSCLC. Six patients had a CTC grade 4 change in laboratory safety data during the study. Four patients experienced a grade 4 hypercalcemia: 1 (3.6%), 2 (6.1%), and 1 (3.2%) in the ALD518 80mg, 160mg and placebo groups, respectively, and there was 1 patient with grade 4 GGT elevation (placebo) and 1 patient with grade 4 hypokalemia (ALD518 160mg). There were no treatment related differences in vitals sign or 12-lead ECG data. The mean (±SD) values for Hb, hematocrit (Hct), mean corpuscular Hb (MCH) and platelet counts are listed below: 38/93 pts treated with ALD518 and 10/31 given placebo had a pre-dose Hb =< 11g/dL. 24 of these pts on ALD518 and 7 of these pts on placebo remained in the study at week 4. 14/24 pts on ALD518 and 0/7 on placebo had raised their Hb from =< 11g/dL to >= 12g/dL. Conclusions: ALD518 increased Hb, Hct, MCH in NSCLC pts and raised Hb to >= 12g/dL in 58% of pts with a Hb =< 11g/dL at baseline. There was also a modest fall in platelet count observed in patients treated with ALD518 but no patients had a CTC grade 4 thrombocytopenia and only one patient (ALD518 160mg group) had a grade 3 thrombocytopenia at one time point. There were no major safety signals related to the administration of ALD518. Further study of ALD518 as a novel non-erythropoietic stimulating agent for cancer-related anemia is warranted. Disclosures: Schuster: Alder Biopharmaceuticals Inc: Honoraria. Rigas: Alder Biopharmaceuticals inc: Honoraria. Smith:Alder Biopharmaceuticals Inc: Employment.

scholarly journals Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma

2021 ◽  
Vol 9 (4) ◽  
pp. e002203
Author(s):  
Georgia M Beasley ◽  
Smita K Nair ◽  
Norma E Farrow ◽  
Karenia Landa ◽  
Maria Angelica Selim ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Phase I Trial ◽  
Clinical Investigation ◽  
Objective Response ◽  
Complete Response ◽  
Primary Objective ◽  
Mitogen Activated Protein Kinase ◽  
Open Label ◽  
Serious Adverse Events

BackgroundWhile programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) antagonists have improved the prognosis for many patients with melanoma, around 60% fail therapy. PVSRIPO is a non-neurovirulent rhinovirus:poliovirus chimera that facilitates an antitumor immune response following cell entry via the poliovirus receptor CD155, which is expressed on tumor and antigen-presenting cells. Preclinical studies show that oncolytic virus plus anti-PD-1 therapy leads to a greater antitumor response than either agent alone, warranting clinical investigation.MethodsAn open-label phase I trial of intratumoral PVSRIPO in patients with unresectable melanoma (American Joint Committee on Cancer V.7 stage IIIB, IIIC, or IV) was performed. Eligible patients had disease progression on anti-PD-1 and V-raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen activated protein kinase kinase (MEK) inhibitors (if BRAF mutant). The primary objective was to characterize the safety and tolerability of PVSRIPO. Twelve patients in four cohorts received a total of 1, 2 or 3 injections of PVSRIPO monotherapy, with 21 days between injections.ResultsPVSRIPO injections were well tolerated with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) reported. All adverse events (AEs) were grade (G) 1 or G2 (G1 pruritus most common at 58%); all but two PVSRIPO-treatment related AEs were localized to the injected or adjacent lesions (n=1 G1 hot flash, n=1 G1 fatigue). Four out of 12 patients (33%) achieved an objective response per immune-related response criteria (two observations, 4 weeks apart), including 4/6 (67%) who received three injections. In the four patients with in-transit disease, a pathological complete response (pCR) was observed in two (50%) patients. Following study completion, 11/12 patients (92%) reinitiated immune checkpoint inhibitor-based therapy, and 6/12 patients (50%) remained without progression at a median follow-up time of 18 months.ConclusionIntratumoral PVSRIPO was well tolerated. Despite the limited number of PVSRIPO treatments relative to the overall lesion burden (67% patients>5 lesions), intratumoral PVSRIPO showed promising antitumor activity, with pCR in injected as well as non-injected lesions in select patients.Trial registration numberNCT03712358

Acupuncture for postprandial distress syndrome: a randomized controlled pilot trial

2020 ◽  
Vol 38 (5) ◽  
pp. 301-309
Author(s):  
Jian-Feng Tu ◽  
Jing-Wen Yang ◽  
Li-Qiong Wang ◽  
Yang Zheng ◽  
Li-Wen Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Symptom Severity ◽  
Primary Outcome ◽  
Distress Syndrome ◽  
Pilot Trial ◽  
Treatment Protocol ◽  
Sham Acupuncture ◽  
Serious Adverse Events ◽  
Postprandial Distress Syndrome ◽  
End Of Treatment

Background: Evidence for treating postprandial distress syndrome with acupuncture is limited. Aim: We aimed to evaluate the feasibility of verum acupuncture versus sham acupuncture in patients with postprandial distress syndrome. Methods: A total of 42 eligible patients were randomly allocated to either verum acupuncture or sham acupuncture groups in a 1:1 ratio. Each patient received 12 sessions over 4 weeks. The primary outcome was the response rate based on the overall treatment effect (OTE) 4 weeks after randomization. Secondary outcomes included dyspepsia symptom severity and adverse events. Results: In each group, 19 patients (91.5%) completed the study. Thirteen patients receiving verum acupuncture and seven patients receiving sham acupuncture were classified as responders according to OTE (61.9% vs 33.3%; rate difference 28.6%; p = 0.06). Dyspepsia symptom severity at the end of treatment also differed significantly between verum acupuncture and sham acupuncture groups (5.9 units vs 3.7 units; between-group difference 2.2 (95% CI, 0.2–4.2); p = 0.04). No serious adverse events occurred. Conclusion: Four weeks of acupuncture may represent a potential treatment for postprandial distress syndrome. The treatment protocol and outcome measures used in this trial were feasible. Since this was a pilot study, the efficacy of acupuncture still needs to be determined by a larger, adequately powered trial.

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