scholarly journals A Phase Ib Open Label Clinical Trial of Continuous Once Daily Oral Afatinib (A) Plus Sirolimus (S) in Patients (Pts) with Egfr Mutation Positive (Egfr M+) Nsclc and/or Disease Progression Following Prior Erlotinib (E) or Gefitinib (G)

2014 ◽  
Vol 25 ◽  
pp. iv437 ◽  
Author(s):  
T. Moran ◽  
R. Palmero ◽  
M. Provencio ◽  
A. Insa ◽  
M. Majem ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Disease Progression ◽  
Egfr Mutation ◽  
Open Label ◽  
Once Daily ◽  
Phase Ib

A phase I clinical trial to assess the safety, pharmacokinetics, and antitumor activity of glumetinib (SCC244) in patients with advanced non-small cell lung cancers (NSCLCs).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21702-e21702
Author(s):  
Hua-Jun Chen ◽  
Jin-Ji Yang ◽  
Xuening Yang ◽  
Qing Zhou ◽  
Minghui Sun ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase I ◽  
Dose Escalation ◽  
Advanced Nsclc ◽  
Clinical Activity ◽  
Maximum Plasma ◽  
Open Label ◽  
Elevated Alkaline Phosphatase ◽  
Once Daily

e21702 Background: Aberrant activation of the MET pathway is associated poor prognosis and poor response to standard therapies in cancer patients. Glumetinib (SCC224) is an oral potent and highly selective MET inhibitor. This is an open label, dose-escalation, phase I clinical study to determine the safety, pharmacokinetics and anti-tumor activity in patients with advanced NSCLC regardless of MET status. Methods: Patients with advanced NSCLC failed standard treatments received glumetinib orally according to one of four dose escalation regimens on a 28-day cycle: 100 mg, 200 mg, 300mg and 400 mg once daily, in a Pharmacologically Guided Dose Escalation (PGDE) design (a variation of the standard 3+3 design). The primary endpoints are the incidence of dose limit toxicity (DLT), maximally tolerated dose (MTD), biologically effective dose (BED). The secondary endpoints are treatment-emergent adverse events (TEAE), safety and tolerability, anti-tumor efficacy, pharmacokinetics, and its metabolites. Results: As of Feb 7, 2020, a total of eighteen eligible (18) patients were enrolled into this study: 3 at 100 mg, 3 at 200 mg, 6 at 300 mg and 6 at 400 mg. Only one patient among 6 evaluable patients at 400mg cohort reported one DLT of grade 3 vomiting. Treatment-related adverse events mostly were grade 1 or 2 nausea, vomiting, elevated alkaline phosphatase, elevated conjugated bilirubin, edema, headache, asthenia and decreased appetite. Non-DLT treatment related G3/4 adverse events were peripheral edema (n = 1, 5.5%), hypothyroidism (n = 1, 5.5%). Absorption was rapid after dosing and the median time to reach maximum plasma drug concentration ( Tmax) was 2.0‐6.0 hours. The mean value of half-life(t1/2) in each dose group ranged from 20.43h to 35.36 h. In response to glumetinib, one patient with MET overexpression at 200mg dose level had a best of response of partial response and completed 44 weeks glumetinib treatment, 4 patients (3 with MET amplification) had a best of response of stable disease. Conclusions: Glumetinib was well tolerated at doses up to 400 mg once daily and demonstrated clinical activity in advanced NSCLC with MET alterations. Glumetinib is used in ongoing clinical trials to further explore safety and efficacy in NSCLC. Clinical trial information: NCT03466268.

scholarly journals Factors Associated with Good Patient Outcomes Following Convalescent Plasma in COVID-19: A Prospective Phase II Clinical Trial

2020 ◽  
Author(s):  
Danyal Ibrahim ◽  
Latha Dulipsingh ◽  
Lisa Zapatka ◽  
Reginald Eadie ◽  
Rebecca Crowell ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Length Of Stay ◽  
Hospital Mortality ◽  
Disease Progression ◽  
Phase Ii ◽  
Positive Impact ◽  
Phase Ii Clinical Trial ◽  
Hospital Length Of Stay ◽  
Severe Illness ◽  
Open Label

We conducted a prospective single-arm open-label phase II clinical trial assessing the safety and efficacy of convalescent plasma in hospitalized COVID-19 patients. Convalescent plasma with sufficient IgG titer (1:320) obtained from recovered donors was administered to adult patients with either severe or critical COVID-19 illness. Primary outcomes were adverse events in association with plasma administration, and hospital mortality. Secondary outcomes included disease progression, recovery, length of stay, and hospital discharge. Of the 38 patients included in the analysis, 24 (63%) recovered and were discharged, and 14 (37%) died. Patients who received convalescent plasma early in the disease course (severe illness group) as compared to the patients that received convalescent plasma later in disease progression (critical illness group) had significantly lower hospital mortality 13% vs 55% (p<0.02) and shorter mean hospital length of stay 15.4 vs 33 days (p<0.01). One patient experienced a transient transfusion reaction. No other adverse effects of convalescent plasma infusion were observed. Our results suggest that convalescent plasma is safe and has the potential for positive impact on clinical outcomes including recovery and survival if given to patients early in the course of COVID-19 disease.

Safety and efficacy of GP40061 compared with originator insulin glargine (Lantus®): a randomized open-label clinical trial

2020 ◽  
Vol 9 (4) ◽  
pp. 263-273
Author(s):  
Tatiana L Karonova ◽  
Anna A Mosikian ◽  
Alexander Y Mayorov ◽  
Igor E Makarenko ◽  
Svetlana T Zyangirova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Clinical Trial ◽  
Immune Response ◽  
Type 1 Diabetes ◽  
Insulin Glargine ◽  
Open Label ◽  
Once Daily ◽  
Safety And Efficacy ◽  
Glucose Profiles

Aim: To compare safety (immunogenicity) and efficacy of GP40061 insulin glargine (GP-Gla) and Lantus® (Sanofi glargine, Sa-Gla) in people with diabetes mellitus. Materials & methods: This randomized open-label, 26-week clinical trial enrolled 180 Type 1 diabetes mellitus patients (HbA1c 6.5–12.0%), randomized 1:1 to once daily GP-Gla (n = 90) or Sa-Gla (n = 90). The primary end point was immune response at 26th week. Results: The frequency of immune response was similar in GP-Gla and Sa-Gla (p = 1.000). Groups were similar in terms of other safety end points. Mean HbA1c change from baseline was -0.66% for GP-Gla and -0.77% for Sa-Gla, and did not differ between groups (p = 0.326). Insulin doses, fasting plasma glucose and seven-point glucose profiles were similar between groups. Conclusion: GP-Gla and Sa-Gla demonstrated similar safety and efficacy. ClinicalTrials.gov Identifier: NCT04022993

A phase II trial of LEE011 in combination with everolimus in the treatment of advanced well differentiated neuroendocrine tumors of foregut origin.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS546-TPS546 ◽  
Author(s):  
Nitya Prabhakar Raj ◽  
Virginia Kelly ◽  
Jennifer A. Chan ◽  
A. Dasari ◽  
Marinela Capanu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Disease Progression ◽  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Drug Combination ◽  
Objective Response ◽  
Metastatic Breast ◽  
Open Label ◽  
Well Differentiated

TPS546 Background: Changes in the retinoblastoma (Rb) tumor suppressor pathway are believed to contribute to the development of well differentiated neuroendocrine tumors (WDNETs). In the pre-clinical setting, loss or downregulation of proteins that normally inhibit the cyclin dependent kinases Cdk4 and Cdk6 have contributed to NET development. Separately, rigorous investigation of everolimus in WDNETs has demonstrated a survival benefit in this patient (pt) population. Pre-clinical data suggests that the Cdk4/Cdk6 inhibitor LEE011 is synergistically active with everolimus. The aim of this study is to evaluate the efficacy and safety of LEE011 in combination with everolimus in pts with advanced WDNETs of foregut origin (thymic, bronchopulmonary, gastric, duodenal, pancreatic). Methods: This study is a multicenter, non-randomized, open-label phase II clinical trial using a Simon two stage optimal design. Main inclusion criteria include: adult patients with WDNET of foregut origin, low to intermediate grade, unresectable and/or metastatic, disease progression ≤ 12 months prior to enrollment, ECOG 0-1. Between 15 and 43 patients will be enrolled from three sites across the US. LEE011 300mg daily, 3 weeks on and 1 week off, in combination with everolimus 2.5mg daily (final dosing based on phase 1b clinical trial performed in metastatic breast cancer; LEE011X2106) will be administered orally until disease progression, unacceptable toxicity, investigator decision, or pt withdrawal. All enrolled pts will be followed by telephone contact for overall survival until death or consent withdrawal. The primary endpoint, progression free survival, will be assessed based on radiographic review by RECISTv1.1. Main secondary endpoints include establishing the safety of this drug combination in this patient population, objective response rate, clinical benefit rate, and overall survival. Correlative objectives include exploring the effect of this drug combination on biomarkers related to the Rb pathway and/or WDNET pathogenesis. This trial began enrollment in 2/27/2017, with 10 patients enrolled to date. Clinical trial information: NCT03070301.

A clinical trial for the safety and immunogenicity of a DNA-based immunotherapy in men with biochemically (PSA) relapsed prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14634-e14634 ◽  
Author(s):  
Neal D. Shore ◽  
Elisabeth I. Heath ◽  
Luke T. Nordquist ◽  
Heather H. Cheng ◽  
Kamalnayan Bhatt ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Disease Progression ◽  
Open Label ◽  
Median Serum ◽  
Definitive Therapy ◽  
Grade 3 ◽  
Ecog Ps ◽  
Dose Levels ◽  
Site Pain

e14634 Background: Introducing amino acid sequence changes in highly expressed self-antigens for prostate cancer (PCa) patients (pts) might lead to avoidance of immune tolerance. We evaluated a DNA vaccine (INO-5150) including SynCon PSA and PSMA. Administration of INO-5150 to PCa pts along with plasmid encoded adjuvant IL-12 (INO-9012) via electroporation (EP) is postulated to break tolerance, resulting in antigen-specific immune responses which could lead to stabilization of disease progression. Methods: Phase I, open-label, multicenter study of PCa pts post-definitive therapy with a rising PSA ≥ 1.0 ng/ml after surgery, or ≥ 2.0 ng/ml above nadir after RT and PSADT > 3 months, testosterone > 150 ng/dL, no concomitant androgen deprivation therapy and no evidence of metastases within 12 months. We evaluated safety, tolerability and for efficacy signals. INO-5150 low (2 mg, arms A and C) or high (8.5 mg, arms B and D) dose with or without INO-9012 (1 mg) was administered IM followed by EP in total 4 dosing arms on Day 0 and at Wks 3, 12, and 24 in 60 planned pts (15/arm). Pts were followed for 72 Wks. Results: 62 pts, 16 each in arms A and D and 15 in B and C were enrolled. Median age: 69.5 yrs (range 55.4-87.7), Gleason score: 7 (5-10), time from initial diagnosis: 8.2 yrs (0.5-23.8) and ECOG PS: 0 (0-1). As of data cutoff of 23Jan17, 52 pts had EOT visit, 7 withdrawn from treatment and 6 (10%) reported disease progression, 3 biochemical and 3 radiographic. Median serum PSA at enrollment was 4.6 ng/mL (range 1.2, 113.7) and at EOT was 6.5 ng/mL (0.1, 73.6). Median PSADT at enrollment was 8.7 months (3.1, 218.1) and at EOT it was 3.1 months (-23.1, 100.0). Safety: no reports of Grade 4-5 SAEs. 6 Grade 3 SAEs in 5 pts: presyncope, cardiac disorder, fall, neoplasm, ALT and AST elevation. Grade 1-3 AEs reported in 51 (82%) pts: 12 (75%) in Arm A, 13 (87%) B, 13 (87%) C, and 13 (81%) in D. Common AEs were injection site pain (24/39%), swelling (14/23%), erythema (14/23%), all Grade 1-2. Conclusions: INO-5150 (+) and (-) INO-9012 was generally safe and well-tolerated at all 4 dose levels in this patient population. Preliminary data suggest PSA stabilization in some patients. Immune analyses are ongoing. (NCT02514213) Clinical trial information: NCT02514213.

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