Anti-Infective Agents

All Drugs and Chemicals

Micafungin

Clotrimazole

Miconazole

Antifungal Agents

Echinocandins

Beta-1,3-glucan

Subjects will be administered 5 mg/kg of micafungin intravenously as a ONE TIME dose.

For patients undergoing Hematopoietic Stem Cell Transplant (HSCT), Micafungin will be given on during rest days (i.e. days when no chemotherapy is administered) and blood for pharmacokinetic measurements will be drawn over next 96 hours.

Following this, further anti-fungal coverage will be at the discretion of the patient's attending physician. (I.e. other antifungal agent(s) or Micafungin at a standard clinical dose; repeat doses of 5mg/kg will NOT be administered.)

Micafungin (trade name Mycamine) is an echinocandin antifungal drug developed by Astellas Pharma. It inhibits the production of beta-1,3-glucan, an essential component of fungal cell walls. Micafungin is administered intravenously. It received final approval from the U.S. Food and Drug Administration on March 16, 2005, and gained approval in the European Union on April 25, 2008.

Parinda Mehta, MD

The purpose of this research study is to examine the pharmacokinetics (the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body) of micafungin when it is given at 5mg/kg dose to immunocompromised children as anti-fungal prophylaxis. These children are at high risk for developing invasive fungal disease due to their compromised immunity and associated variable degree and duration of neutropenia. Currently, children who receive micafungin are given daily or alternate day dosing. The investigators will give a ONE TIME dose of micafungin and draw PK levels up to 96 hours post-infusion. The investigators goal is to obtain comparable micafungin drug concentrations at the end of 96 hours (4 days) as compared to lower dose at every 24 hour dosing. The investigators dosing proposal is likely to be effective prophylaxis for immunocompromised patients and would broaden its applicability to larger populations.

Disseminated fungal infection is a major cause of morbidity and mortality in immunocompromised children. Many of the drugs used for fungal prophylaxis have been associated with renal and hepatic toxicity. Also, breakthrough infections have been reported with the use of some of the oral agents due to poor oral absorption. An alternative approach is the use of intravenous micafungin for fungal prophylaxis. Micafungin has a distinct advantage due to its better safety profile, specifically in terms of hepatic and renal toxicity. Currently, children who receive micafungin are given daily or alternate day dosing (based on their last Pk study, Mehta et al 2010). The investigators objective is to examine the pharmacokinetics of micafungin when it is given on a less frequent schedule. The investigators hypothesize that a single dose of micafungin (at 5mg/kg) every 4 days will provide drug exposure equivalent to daily dosing (at 1mg/kg) while reducing administration costs and improving patient convenience (with essentially twice a week dosing regimen). Both animal and adult data support the use of this approach. Fifteen patients will be enrolled on this study and will be given a SINGLE DOSE of micafungin antifungal prophylaxis (5 mg/kg). Blood samples will be drawn for pharmacokinetic measurements after administration of micafungin. Plasma concentration data will be analyzed by compartmental and non-compartmental pharmacokinetic analysis. The data will also be analyzed by a population pharmacokinetic approach.

A Pharmacokinetic Study of Pediatric Micafungin Prophylaxis

Micafungin Anti-Fungal Prophylaxis in Immunocompromised Pediatric Patients: A Pharmacokinetic Study

Blood samples from the above time points will be analyzed to study the bodily absorption, distribution, metabolism, and excretion of micafungin

Astellas Pharma Inc

Children's Hospital Medical Center, Cincinnati

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

Gemcitabine

Carboplatin

Cisplatin

Itraconazole

Hydroxyitraconazole

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Patients will receive intravenous doses of cisplatin 80 mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 6 cycles + itraconazole 200 mg oral tablet daily, on a 21-day cycle.

Alternatively, Carboplatin may be used instead of Cisplatin, Carbplatin AUC 5 DAY 1 only Dose = AUC x (GFR + 25) IV in 250 mL Normal Saline over 30 minutes

Patients will receive intravenous doses of cisplatin 80 mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 6 cycles.

Alternatively, Carboplatin may be used instead of Cisplatin, Carbplatin AUC 5 DAY 1 only Dose = AUC x (GFR + 25) IV in 250 mL Normal Saline over 30 minutes

itraconazole 200 mg oral tablet daily, on a 21-day cycle.

Itraconazole 200 mg

intravenous doses of cisplatin 80 mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 6 cycles.

Alternatively, Carboplatin may be used instead of Cisplatin, Carbplatin AUC 5 DAY 1 only Dose = AUC x (GFR + 25) IV in 250 mL Normal Saline over 30 minutes

Chemotherapy

Asmaa WH Mohamed, Master

Amr Sh Tawfik, MD

Amr sh Tawfik, MD

Amr Shafik Tawfik, MD

Circulating levels of angiogenic factors have been correlated with aggressive tumor growth, prediction of metastasis and prognosis in a wide range of solid tumors, including non-small cell lung cancer.

Food and Drug Administration (FDA) approved Itraconazole as an anti-angiogenic agent including both Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), and inhibited phosphorylation of the primary angiogenic receptors for these factors in 2007 and also known as an inhibitor of Hedgehog signalling, AKT (protein kinase B)/mechanistic target of rapamycin (mTOR) signaling adding its induction of autophagic cell death function based on cellular and laboratory studies, and allowed its use in phase II trials in prostate, lung and skin cancer.

Itraconazole also interferes directly with mitochondrial Adenosine triphosphate (ATP) production, leading to the activation of the adenosine monophosphate (AMP) -activated protein kinase pathway and subsequent inhibition of mTOR pathway (Head et al., 2015).

Testing Itraconazole on experimental settings was associated also with tumor hypoxia, as proved by induction of tumor-specific expression of Hypoxia-inducible factor 1-alpha (HIF1α), as well as decreased tumor micro-vessel load

Lung cancer is the leading cause of cancer death in the United States

The American Cancer Society estimates lung cancer incidence in the United States for 2018 to be about 234,030 and about 154,050 deaths.

In 2012, GLOBOCAN estimated that 1.8 million people were diagnosed with lung cancer, accounting for about 13% of total cancer diagnoses.

Lung cancer death rates declined 45% from 1990 to 2015 among men and 19% from 2002 to 2015 among women. From 2005 to 2014, the rate of new lung cancer cases dropped by 2.5% per year in men and 1.2% per year in women, These differences reflect historical patterns in tobacco use, where women began smoking in large numbers many years later than men, and were slower to quit .

World Health Organization (WHO) divides lung cancer into 2 major classes based on its biology, therapy, and prognosis: non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

The NSCLC subtype accounts for 87% of lung cancer cases with its most common types to be adenocarcinomas where it is approximately 40% of lung cancers.

Different factors like age, Performance state, co-morbidities, histology, molecular pathology and last but not least; the patient's preferences should be taken into account along the treatment strategy after a multidisciplinary tumor board discussion, to allow adequate and careful evaluation of the available data to reach the most appropriate management plan and treatment modality for each patient individually (Ung et al., 2016).

Platinum doublets Chemotherapy should be considered in all stage IV and inoperable stage III NSCLC patients with epidermal growth factor receptor (EGFR) and Anaplastic lymphoma kinase (ALK) negative disease, without major comorbidities and Performance state 0-2.

Circulating levels of angiogenic factors have been correlated with aggressive tumor growth, prediction of metastasis and prognosis in a wide range of solid tumors, including non-small cell lung cancer.

Food and Drug Administration (FDA) approved Itraconazole as an anti-angiogenic agent including both Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), and inhibited phosphorylation of the primary angiogenic receptors for these factors in 2007 and also known as an inhibitor of Hedgehog signalling, AKT (protein kinase B)/mechanistic target of rapamycin (mTOR) signaling adding its induction of autophagic cell death function based on cellular and laboratory studies, and allowed its use in phase II trials in prostate, lung and skin cancer.

Itraconazole was proved to be among one of the most potent and selective inhibitors of endothelial cell proliferation.

Itraconazole also interferes directly with mitochondrial Adenosine triphosphate (ATP) production, leading to the activation of the adenosine monophosphate (AMP) -activated protein kinase pathway and subsequent inhibition of mTOR pathway (Head et al., 2015).

Testing Itraconazole on experimental settings was associated also with tumor hypoxia, as proved by induction of tumor-specific expression of Hypoxia-inducible factor 1-alpha (HIF1α), as well as decreased tumor micro-vessel load.

Taken together, these data support that Itraconazole may become a promising novel anti-angiogenic agent and In contrast to bevacizumab, Itraconazole is an inexpensive oral agent, currently available in a generic formulation and has been safely administered to thousands of patients as an antifungal drug with an excellent tolerance.

Interventional, Randomized, Controlled, Prospective, Open label, Phase II study.

Itraconazole in Non Small Cell Lung Cancer

The Effect of Itraconazole on the Clinical Outcomes of Patients With Advanced Non Small Cell Lung Cancer Receiving Platinum Based Chemotherapy

According to the sharing protocol of the official affliation

time from treatment initiation to either progression, death from any cause or lost to follow up.

time in months from time of diagnosis to death or date of last contact.

To compare radiological response of patients with advanced lung cancer receiving platinum bases chemotherapy combined with itraconazole to those receiving platinum based chemotherapy only after 3 and 6 cycles of chemotherapy.

Patient's quality of life will be assessed at baseline, after 3 cycles, and at the end of chemotherapy treatment using EORTC modules specific to lung cancer.

Incidence and severity will be evaluated using National Cancer Institute-Common Toxicity Criteria for adverse events (CTCAE V4.03).

Ain Shams University

Doctor

Symptoms and General Pathology

Blood and Lymph Conditions

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Anti-Dyskinesia Agents

Anti-Bacterial Agents

Levofloxacin

Ofloxacin

Cephalosporins

beta-Lactams

Antibiotics, Antitubercular

Mitogens

Fluconazole

Trimethoprim, Sulfamethoxazole Drug Combination

Posaconazole

Trimethoprim

Sulfamethoxazole

Antiprotozoal Agents

Antiparasitic Agents

Anti-Infective Agents, Local

Antimalarials

Patients affected by myelodysplastic syndrome enrolled in the observational study

Antibiotic and antifungal drugs

Livio Pagano, Dr.

The purpose of this study is to observe the number of new cases of infections per population in a given time period and their characteristics in a pathology (myelodysplastic syndrome, MDS)that involves ineffective production (or dysplasia) of a class of blood cells.

The scarcity and the inadequacy of data make impossible the writing of evidence-based recommendations for prevention and management of infections in myelodysplastic syndrome.

The aim of this study is to evaluate the incidence and the spectrum of the infections of MDS patients. Will be also evaluated potential risk factors.

This study could help the definition of the optimal management of MDS patients in terms of prophylaxis of the infective complications and in terms of the correct administration of growth factors.

Observational Evaluation of Infective Risk in Myelodysplastic Syndrome Patients

Observational Prospective Multicenter Study to Evaluate the Infective Risk in Myelodysplastic Syndrome Patients: Antimicrobial Prophylaxis and Granulocyte Growth Factors.

Infectious events are fungal and antibiotic events

Gruppo Italiano Malattie EMatologiche dell'Adulto

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Infections

Skin and Connective Tissue Diseases

Kidney Diseases

Communicable Diseases

Exanthema

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Antirheumatic Agents

Dermatologic Agents

Everolimus

Cyclosporine

Cyclosporins

Mycophenolic Acid

Tacrolimus

Sirolimus

Voriconazole

Immunosuppressive Agents

Patients treated for their regular patient care with mycophenolic acid.

Patients treated for their regular patient care with cyclosporin.

Patients treated for their regular patient care with tacrolimus.

Patients treated for their regular patient care with sirolimus.

Patients treated for their regular patient care with everolimus.

Patients treated for their regular patient care with voriconazole.

Patients treated for their regular patient care with posaconazole.

Patients treated for their regular patient care with itraconazole.

Patients treated for their regular patient care with fluconazole.

The association between conventional venous sampling and finger prick dried blood spot (DBS) will be associated by drawing blood in both ways.

blood drawing

Roger Bruggemann, PharmD PhD

This is a clincial validation study of a dried blood spot (DBS) method for the analysis of immunosuppressive and antifungal agents currently subject of therapeutic drug monitoring (TDM) in a pediatric population.

The primary goal is to clinically validate a finger prick DBS method compared to conventional venous sampling for the analysis of 5 immunosuppressive and 4 azole antifungal drugs in the pediatric population. Secondairy goals include feasibility of the finger prick DBS method in the target population, to design an inventory of costs that will be incurred in future health-economic analyses and to construct a population PK model based on the available data collected for the primariy goal.

Therapeutic drug monitoring (TDM) offers the possibility to individualize and improve a patient's pharmacological treatment, based on the measurement of drug concentrations in biological samples. Conventionally, TDM is performed with blood or plasma obtained by venous blood sampling. This method is associated with several challenges such as i) the need for the patient to travel to the hospital or health center; ii) special conditions for sample transport to guarantee stability of the analyte and to decrease the biohazard risk; iii) sampling times not always representing the preferable peak or trough concentrations; iv) the method being invasive and v) delay of the outcome of the analyses with regard to the outpatient visit.

The Dried Blood Spot (DBS) may offer a solution for all these challenges. DBS is thought to offer benefits over plasma venous sampling for TDM. The main purpose of the PROTECT (Personalized treatment of immunosuppressive and antifungal drugs through continuous home based monitoring with Dried Blood Spot sampling techniques in pediatric patients) study is to improve therapeutic management and patient participation in pediatric patients treated with antifungal and immunosuppressive agents. PROTECT is mainly financed by a ZonMW grant 'Goed Gebruik Geneesmiddelen'.

Four patient organizations are actively involved in the PROTECT study.

Objective of the study:

Primairy To clinically validate a finger prick DBS method compared to conventional venous sampling for the analysis of 5 immunosuppressive and 4 azole antifungal drugs in the pediatric population. Secondairy

* Feasibility of the novel finger prick DBS method in the pediatric population will be assessed. This includes scoring of relevant characteristics (attributes) of blood drawing methods for TDM, evaluation of the experience and attitude of both patients and parents regarding finger prick DBS sampling and evaluation of the understanding of the written instructions provided for performing the finger prick at home. The data obtained in this validation study will be used for the implementation of the DBS in therapeutic drug monitoring (TDM) being a less invasive procedure, and as a base for a discrete choice-experiment as part of the HTA.
* To design an inventory of types of costs that will be incurred in the process of DBS-based and conventional TDM as a preparation step for later health economic analysis.
* Data from this study will be used to construct a population pharmacokinetic model to optimize dosing and design new guidelines.

This is an observational mono-centre study in which DBS sampling is compared with conventional sampling for TDM in a steady state situation.

Clearly, information on feasibility of DBS sampling in children and on costs relevant to DBS sampling in children can only be obtained through actual sampling in children.

Plasma without DNA, blood with DNA and dried blood spot (with DNA)

Clinical Validation of a Dried Blood Spot Method for Analysis of Immunosuppressives and Antifungals in Pediatrics

Clinical Validation of a Dried Blood Spot (DBS) Method for the Analysis of Immunosuppressive and Antifungal Drugs in Pediatric Patients (Part of the PROTECT Study).

The outcome measure is a composite of several blood concentrations, obtained by three individual blood drawing moments per patient. The related endpoint is the evaluation of the association between the concentration obtained by venous sampling and the concentration obtained by means of DBS sampling. The predictive performance of the DBS method as a measure for the venous concentration will be evaluated.

The related endpoint is the response to a questionnaire. Results will be used to prepare implementation of the novel method for home-based monitoring as well as to prepare a HTA analysis.

Costs of blood drawing methods will be collected.The cost types will function as a basis for future HTA analysis of this novel sampling method compared to conventional venous sampling.

Blood concentrations will be used to calculate the area under the concentration time curve (AUC). The outcome measure will be a composite of population estimates of the pharmacokinetic parameters AUC, maximal concentration (Cmax), time to maximal concentration (Tmax), clearance (CL), volume of distribution (Vd) and elimination half-life (t1/2).

ZonMw: The Netherlands Organisation for Health Research and Development

Radboud University Medical Center

Leukemia

Acute Disease

Neoplasms by Histologic Type

Disease Attributes

Acute Graft Versus Host Disease

Patients received 50 mg micafungin intravenously once daily from the initiation of induction chemotherapy to recovery of neutrophil count (absolute neutrophil count \> 500/μg for three consecutive days), suspected fungal infection, or occurrence of drug-related toxicity.

Youngil Koh, Dr.

The purpose of this study is to determine whether prophylaxis with micafungin is effective in the induction chemotherapy for newly diagnosed acute leukemia patients.

Medically fit patients with newly diagnosed acute leukemia received 50 mg micafungin intravenously once daily from the initiation of first induction chemotherapy to recovery of neutrophil count, suspected fungal infection, or unacceptable drug-related toxicity.

Micafungin Prophylaxis During 1st Induction Chemotherapy for De Novo Acute Leukemia

Phase II Trial of Micafungin Prophylaxis During Induction Chemotherapy for Patients With Acute Leukemia

proven fungal infection: proven by positive culture for fungus with symptoms and signs of a fungal infection probable fungal infection: direct or indirect detection (galactomannan antigen or serum β-D-glucan) with clinical and radiographic findings possible fungal infection: sufficient clinical evidence for fungal infection was present without mycological evidence

The survival of patients till 12 weeks after induction chemotherapy

The outcomes of non-relapse mortality: The incidence of death without a previous relapse or progression

Seoul National University Hospital

Serious adverse events: life-threatening adverse events Other adverse events: non-serious adverse events during treatment

Adverse Events

The baseline characteristics of total patients

Micafungin Prophylaxis

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

South Korea

Region of Enrollment

Pf. Youngil Koh

Number of Participants With Proven/Probable/Possible Invasive Fungal Infection

Survival Outcome

Overall Survival

Non-relapse mortality was defined as the incidence of death without a previous relapse or progression.

Non-relapse Mortality

50 mg micafungin intravenously once daily from the initiation of induction chemotherapy to recovery of neutrophil count (absolute neutrophil count \> 500/μg for three consecutive days), suspected fungal infection, or occurrence of drug-related toxicity

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Pharmacokinetic Study of Pediatric Micafungin Prophylaxis	NCT02057289	Immunocompromis... Bone Marrow Tra... Cancer	Micafungin	6 Months - 10 Years	Children's Hospital Medical Center, Cincinnati
Itraconazole in Non Small Cell Lung Cancer	NCT03664115	Lung Cancer	Itraconazole 20... Chemotherapy	18 Years -	Ain Shams University
Observational Evaluation of Infective Risk in Myelodysplastic Syndrome Patients	NCT01951430	Myelodysplastic...	Antibiotic and ...	18 Years -	Gruppo Italiano Malattie EMatologiche dell'Adulto
A Pharmacokinetic Study of Pediatric Micafungin Prophylaxis	NCT02057289	Immunocompromis... Bone Marrow Tra... Cancer	Micafungin	6 Months - 10 Years	Children's Hospital Medical Center, Cincinnati
Clinical Validation of a Dried Blood Spot Method for Analysis of Immunosuppressives and Antifungals in Pediatrics	NCT02329808	Hematologic Dis... Oncology Proble... Kidney Diseases Transplantation...	blood drawing	2 Years - 18 Years	Radboud University Medical Center
Micafungin Prophylaxis During 1st Induction Chemotherapy for De Novo Acute Leukemia	NCT02440178	Acute Leukemia	Micafungin	18 Years - 75 Years	Seoul National University Hospital
Observational Evaluation of Infective Risk in Myelodysplastic Syndrome Patients	NCT01951430	Myelodysplastic...	Antibiotic and ...	18 Years -	Gruppo Italiano Malattie EMatologiche dell'Adulto

Spots Global Cancer Trial Database for antifungal

Every month we try and update this database with for antifungal cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for antifungal

Every month we try and update this database with for antifungal cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for antifungal cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.