Trimetrexate: a second generation folate antagonist in clinical trial.

1987 ◽  
Vol 5 (12) ◽  
pp. 2032-2040 ◽  
Author(s):  
J T Lin ◽  
J R Bertino
Keyword(s):  
Clinical Trials ◽  
Antitumor Activity ◽  
Pneumocystis Pneumonia ◽  
Dose Effect ◽  
Small Cell Lung ◽  
Phase Ii Trials ◽  
Neck Tumors ◽  
Nonhematologic Toxicity ◽  
Leucovorin Rescue ◽  
New Treatment

Trimetrexate is a promising new lipophilic antifolate with antitumor and antimicrobial activity, which is currently undergoing clinical trials. It differs from methotrexate in its transport and intracellular retention, and may be useful against tumors resistant to methotrexate because of impaired transport or deficient polyglutamylation. In preclinical studies, it has demonstrated a broader spectrum of antitumor activity than methotrexate, and appears to have synergistic antitumor activity when combined with a number of other agents. In clinical trials, the primary toxicity has been hematologic, with rapid recovery and no evidence of cumulative dose effect. Nonhematologic toxicity has been sporadic. Preliminary results of phase II trials indicate activity against breast, non-small-cell lung, and head and neck tumors. In addition, trimetrexate with simultaneous leucovorin rescue appears to be a promising new treatment for pneumocystis pneumonia in AIDS patients, with minimal toxic side effects.

scholarly journals Clinical Trial Information As a Measure of Quality Cancer Care

2010 ◽  
Vol 6 (3) ◽  
pp. 170-171 ◽  
Author(s):  
Wei Chua ◽  
Stephen J. Clarke
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Cancer Care ◽  
Treatment Options ◽  
Small Cell ◽  
Small Cell Lung ◽  
Quality Cancer Care ◽  
Improved Outcomes ◽  
New Treatment ◽  
Clinical Trial Information

Participation in clinical trials enables patients to access new treatment options. Evidence shows improved outcomes in participants compared with nonparticipants in non–small-cell, lung, breast, colorectal, and testicular cancers.

Single-agent chemotherapy trials in small-cell lung cancer, 1970 to 1990: the case for studies in previously treated patients.

1992 ◽  
Vol 10 (3) ◽  
pp. 484-498 ◽  
Author(s):  
S C Grant ◽  
R J Gralla ◽  
M G Kris ◽  
J Orazem ◽  
E A Kitsis
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Phase Ii Trials ◽  
Previously Treated Patients ◽  
Previously Treated

PURPOSE This review was undertaken (1) to determine the antitumor activity of agents studied in phase II trials in small-cell lung cancer (SCLC) patients, (2) to evaluate the adequacy of published trials, (3) to determine if previously treated patients are suitable for phase II trials in SCLC, and (4) to develop an improved design for phase II trials. DESIGN English-language, single-agent efficacy trials in SCLC, published from 1970 to 1990, were reviewed. Study design and reporting of results were assessed for clinical and statistical methodology. Response rates observed in previously treated patients were compared with those observed in previously untreated patients. RESULTS One hundred forty-one articles evaluating 57 agents in 3,042 patients were reviewed. Eleven drugs were active (defined as a response rate greater than or equal to 20% in a trial with greater than or equal to 14 assessable patients), and 12 were inactive. Due to methodologic problems with the clinical trials, the usefulness of the remaining 34 drugs (60%) remains uncertain. Deficiencies identified in trials include inappropriate sample sizes, poorly defined response criteria, and failure to report important prognostic factors. When studied in adequate trials, all agents known to be active in SCLC had an observed response rate greater than or equal to 10% in previously treated patients. CONCLUSIONS Over the past 2 decades, phase II trials in SCLC have failed in their primary task of effectively identifying agents that warrant further clinical study and rejecting inactive agents. If only previously treated patients had been entered into these trials, no useful agent would have been missed provided that a lower observed response rate had been used as evidence of antitumor activity. We propose a two-stage sequential study design, entering previously treated patients, for future phase II trials in SCLC.

Phase II trial of a 3-hour infusion of paclitaxel in previously untreated patients with advanced non-small-cell lung cancer.

1996 ◽  
Vol 14 (1) ◽  
pp. 142-148 ◽  
Author(s):  
M J Millward ◽  
J F Bishop ◽  
M Friedlander ◽  
J A Levi ◽  
D Goldstein ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Small Cell ◽  
World Health ◽  
Small Cell Lung ◽  
Phase Ii Trials

PURPOSE To determine the antitumor activity and toxicity of paclitaxel administered as a 3-hour infusion in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Fifty-one patients with advanced measurable or assessable NSCLC and performance status 0 to 2 who had not received prior chemotherapy were treated with paclitaxel 175 mg/m2 over 3 hours with premedication. Cycles were repeated every 3 weeks for a maximum of nine cycles. Most patients had prior radiotherapy (57%), extrathoracic metastatic disease (65%), and measurable disease (75%). Twenty-two percent had previously untreated stage III disease. RESULTS The objective response rate was five of 51 (10%; 95% confidence interval, 3% to 21%). No subgroup with a higher response rate could be identified. There were no complete responses (CRs) and all responses lasted less than 5 months. Treatment was well tolerated with brief World Health Organization (WHO) grade IV neutropenia in only 16% of patients. Grade III/IV myalgia/athralgia occurred in 22% of patients. No significant hypersensitivity reactions occurred. CONCLUSION The antitumor activity of this dose and schedule appears inferior to that reported in previously published phase II trials in NSCLC that used higher doses of paclitaxel infused over 24 hours, although confidence intervals for response overlap. Determining the optimal dose and schedule for using paclitaxel in NSCLC requires further investigation, and these results should caution against using shorter infusions outside appropriate clinical trials.

scholarly journals BEBT-109, a pan-mutant-selective EGFR inhibitor with potent antitumor activity in EGFR-mutant non-small cell lung cancer

2021 ◽  
Vol 14 (2) ◽  
pp. 100961
Author(s):  
Fushun Fan ◽  
Minhua Zhou ◽  
Xiaolan Ye ◽  
Zhenxian Mo ◽  
Yaru Ma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Inhibitor ◽  
Small Cell Lung ◽  
Egfr Mutant

278 Phase I clinical trial evaluating the safety of ADP-A2M10 SPEAR T-cells in patients with MAGE-A10+ advanced non-small cell lung cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A303-A303
Author(s):  
George Blumenschein ◽  
Siddhartha Devarakonda ◽  
Melissa Johnson ◽  
Victor Moreno ◽  
Justin Gainor ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Dose Level ◽  
Cell Lung Cancer ◽  
Lentiviral Vector ◽  
Small Cell ◽  
Small Cell Lung ◽  
Human Dose

BackgroundADP-A2M10 SPEAR T-cells are genetically engineered autologous T-cells that express a high affinity MAGE-A10-specific T-cell receptor targeting MAGE-A10+tumors in the context of HLA-A*02. This trial is now complete (NCT02592577).MethodsThis first-in-human dose escalation trial utilized a modified 3+3 design to evaluate safety and antitumor activity. Eligible patients (pts) were HLA-A*02+ with advanced non-small cell lung cancer (NSCLC) expressing MAGE-A10. Pts underwent apheresis; T-cells were isolated, transduced with a lentiviral vector containing the TCR targeting MAGE-A10, and expanded. Pts underwent lymphodepletion (LD) with varying doses/schedules of fludarabine (Flu) and cyclophosphamide (Cy) prior to receiving ADP-A2M10. ADP-A2M10 was administered at Dose Level (DL) 1= 0.1×109, DL2 0.5–1.2×109, and DL3/Expansion= 1.2–15×109 transduced cells.ResultsAs of Jan 10, 2020, 11 pts (6 male/5 female) with NSCLC (3 squamous cell, 7 adenocarcinoma, 1 adenosquamous) were treated. Five, 3 and 3 pts received cells at DL1, DL2, and DL3/Expansion, respectively. The most frequently reported adverse events ≥ Grade 3 were lymphopenia (11), leukopenia (9), neutropenia (8), anemia (6), thrombocytopenia (5), and hyponatremia (5). Three pts reported CRS (Grades 1, 2, and 4, respectively). One pt received the highest dose of LD (Flu 30 mg/m2 Day 1 4 and Cy 1800 mg/m2 Day 1–2) prior to a second infusion and had a partial response (PR). This pt subsequently developed aplastic anemia and died. Responses included: 1 pt – PR, 3 pts - stable disease, 2 pts – progressive disease, 1 pt - too early to determine, 4 pts - off-study prior to tumor assessment. SPEAR T-cells were detectable in peripheral blood from pts at each dose level, and in tumor tissue from pts at DL1 and DL3.ConclusionsADP-A2M10 SPEAR T-cells have shown acceptable safety and no evidence of toxicity related to off-target binding or alloreactivity. Given the minimal antitumor activity and the discovery that MAGE-A10 expression frequently overlaps with MAGE-A4 expression, the clinical program has closed. Several trials with SPEAR T-cells targeting MAGE-A4 are ongoing (https://bit.ly/35htsZK).Trial RegistrationNCT02592577Ethics ApprovalThe trial was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines and was approved by local authorities. An independent ethics committee or institutional review board approved the clinical protocol at each participating center. All the patients provided written informed consent before study entry.

scholarly journals Treatment for mitochondrial diseases

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Tongling Liufu ◽  
Zhaoxia Wang
Keyword(s):  
Clinical Trials ◽  
Nuclear Dna ◽  
Mitochondrial Diseases ◽  
Cochrane Collaboration ◽  
Potential Bias ◽  
Leber Hereditary Optic Neuropathy ◽  
Pharmacological Agents ◽  
Unpublished Studies ◽  
New Treatment ◽  
Allotopic Expression

AbstractMitochondrial diseases are predominantly caused by mutations of mitochondrial or nuclear DNA, resulting in multisystem defects. Current treatments are largely supportive, and the disorders progress relentlessly. Nutritional supplements, pharmacological agents and physical therapies have been used in different clinical trials, but the efficacy of these interventions need to be further evaluated. Several recent reviews discussed some of the interventions but ignored bias in those trials. This review was conducted to discover new studies and grade the original studies for potential bias with revised Cochrane Collaboration guidelines. We focused on seven published studies and three unpublished studies; eight of these studies showed improvement in outcome measurements. In particular, two of the interventions have been tested in studies with strict design, which we believe deserve further clinical trials with a large sample. Additionally, allotopic expression of the ND4 subunit seemed to be an effective new treatment for patients with Leber hereditary optic neuropathy.

scholarly journals EPID-07. ACCESS TO GLIOBLASTOMA CLINICAL TRIALS FOR RURAL PATIENTS IN THE UNITED STATES FROM 2010–2020

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii79-ii79
Author(s):  
Kathryn Nevel ◽  
Samuel Capouch ◽  
Lisa Arnold ◽  
Katherine Peters ◽  
Nimish Mohile ◽  
...  
Keyword(s):  
United States ◽  
Clinical Trials ◽  
Rural Communities ◽  
The United States ◽  
Interventional Treatment ◽  
Phase Ii Trials ◽  
Treatment Trials ◽  
Rural Sites ◽  
Rural Patients ◽  
Urban Sites

Abstract BACKGROUND Patients in rural communities have less access to optimal cancer care and clinical trials. For GBM, access to experimental therapies, and consideration of a clinical trial is embedded in national guidelines. Still, the availability of clinical trials to rural communities, representing 20% of the US population, has not been described. METHODS We queried ClinicalTrials.gov for glioblastoma interventional treatment trials opened between 1/2010 and 1/2020 in the United States. We created a Structured Query Language database and leveraged Google application programming interfaces (API) Places to find name and street addresses for the sites, and Google’s Geocode API to determine the county location. Counties were classified by US Department of Agriculture Rural-Urban Continuum Codes (RUCC 1–3 = urban and RUCC 4–9 = rural). We used z-ratios for rural-urban statistical comparisons. RESULTS We identified 406 interventional treatment trials for GBM at 1491 unique sites. 8.7% of unique sites were in rural settings. Rural sites opened an average of 1.7 trials/site and urban sites 2.8 trials/site from 1/2010–1/2020. Rural sites offered more phase II trials (63% vs 57%, p= 0.03) and fewer phase I trials (22% vs 28%, p= 0.01) than urban sites. Rural locations were more likely to offer federally-sponsored trials (p< 0.002). There were no investigator-initiated or single-institution trials offered at rural locations, and only 1% of industry trials were offered rurally. DISCUSSION Clinical trials for GBM were rarely open in rural areas, and were more dependent on federal funding. Clinical trials are likely difficult to access for rural patients, and this has important implications for the generalizability of research as well as how we engage the field of neuro-oncology and patient advocacy groups in improving patient access to trials. Increasing the number of clinical trials in rural locations may enable more rural patients to access and enroll in GBM studies.

scholarly journals Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jean-Sélim Driouich ◽  
Maxime Cochin ◽  
Guillaume Lingas ◽  
Grégory Moureau ◽  
Franck Touret ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Exposure ◽  
Clinical Evidence ◽  
Antiviral Effect ◽  
Dose Effect ◽  
Plasma Drug ◽  
Hamster Model ◽  
Viral Genomes ◽  
Antiviral Efficacy ◽  
Repurposed Drugs

AbstractDespite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we use a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment is initiated before or simultaneously to infection, favipiravir has a strong dose effect, leading to reduction of infectious titers in lungs and clinical alleviation of the disease. Antiviral effect of favipiravir correlates with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. Antiviral efficacy is achieved with plasma drug exposure comparable with those previously found during human clinical trials. Notably, the highest dose of favipiravir tested is associated with signs of toxicity in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans.

Sign in / Sign up

Export Citation Format

Share Document