Nervous System Diseases

Substance Related Disorders

All Conditions

Neoplasms

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Neurotoxicity Syndromes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Syndrome

Gastrointestinal Diseases

Poisoning

Chemically-Induced Disorders

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Bone Density Conservation Agents

Vitamins

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Calcium

Folic Acid

Calcium, Dietary

Folinic Acid

Folate

Vitamin B9

Folfox: It includes the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin.

Folfox Protocol

Sara Mohamed Abdel Aziz, Master Student

May Ahmed Shawki, Lecturer

Sara Mohamed Abdel Aziz

Nagwa Ali Sabri, Professor

Diaa Eldin Moussa Sherif, Lecturer

Study the effect of genetic polymorphism (rs1885301, rs4148396 and rs3740066) in the membrane of Multidrug resistance protein 2 (MRP2) encoded by ATP-binding cassette C2 (ABCC2) gene and its genetic expression levels on neurotoxicity in gasrtointestinal cancer patients reciving Oxaliplatin-based chemotherapy.

Several solutes carriers and ATP-binding cassette transporters have been implicated in the influx or efflux of platinum-based chemotherapeutic agents such as cisplatin, carboplatin, and oxaliplatin. The ATP-binding cassette (ABC-) transporter superfamily contains several family members that may confer intrinsic or acquired multidrug resistance (MDR) by extruding anticancer agents or their metabolites from cells and suppression of such transporters may lead to sensitisation to cytostatic agents. Multidrug resistance protein 2 (MRP2), encoded by the ATP-binding cassette C2 (ABCC2) gene , is an efflux pump located on the apical membrane of many polarized cells, which transports conjugate compounds by an ATP-dependent mechanism like oxaliplatin. Single nucleotide polymorphisms (SNPs) in genes involved in drug transport like ABCC2 gene may lead to higher intracellular oxaliplatin accumulation in the dorsal root ganglia and thus increased risk of Oxaliplatin-induced peripheral neurotoxicity (OXPN). Enhanced ABCC2 expression can lead to decreased cellular glutathione content. Glutathione is needed for oxaliplatin detoxification via conjugation, and it was reported that low glutathione intra- cellular levels can cause increased oxaliplatin cytotoxicity. Moreover, ABCC2 mediates the export of the oxaliplatin-glutathione conjugated form, and ABCC2 overexpressing cells were resistant to platinum derivatives.

the Effect of ABCC2 Genetic Polymorphism on Neurotoxicity in Gastrointestinal Cancer Patients Receiving Oxaliplatin

The Effect of ATP-Binding Cassette C2 (ABCC2) Transporter Genetic Polymorphism on Neurotoxicity in Gastrointestinal Cancer Patients Receiving Oxaliplatin -Based Chemotherapy

the effect of genetic polymorphism (rs1885301, rs4148396 and rs3740066) in the membrane of Multidrug resistance protein 2 (MRP2) encoded by ATP-binding cassette C2 (ABCC2) gene and its genetic expression levels on neurotoxicity in gastrointestinal cancer patients reciving Oxaliplatin-based chemotherapy.

Grading of peripheral neuropathy using National Cancer Institute's Common Toxicity Criteria for Adverse Event ( NCI- CTCAE V5.0 ) will be assessed at baseline and before each cycle.

Ain Shams University

pharmacist

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Anti-Inflammatory Agents

Androgens

Prednisone

Satraplatin

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

satraplatin - 80 mg/m\^2 days 1-5 of every 35 day cycle prednisone - 5 mg twice daily every 35 days

80 mg/m\^2 days 1-5 of every 35 day cycle

prednisone

William L Dahut, M.D.

Background:

Satraplatin is an experimental drug that may be of benefit to patients with prostate cancer.

Prednisone is approved for treating prostate cancer.

The gene excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1) helps repair cell damage caused by satraplatin. It is possible that patients who have a variant of this gene will not benefit from treatment with satraplatin because the drug will not be able to damage the cancer cells effectively.

Objectives:

To determine if satraplatin may help treat prostate cancer in patients with certain variants of the ERCC1 gene.

Eligibility:

Patients with advanced androgen-independent prostate cancer whose disease has not responded to hormonal therapy or at least one type of chemotherapy and whose x-rays, scans or other tests have shown their cancer to be spreading.

Design:

Participants have a blood test to determine if they have a variant of the ERCC1 gene.

Participants take satraplatin by mouth every day for 5 consecutive days out of every 35 days and prednisone by mouth every day. These 35-day treatment cycles may continue for 6 months or longer, depending on the benefits and side effects of the treatment.

During the treatment period, patients undergo the following tests and procedures:

* Blood tests on days 1 of the treatment cycle.
* Weekly blood draws for the first 3 treatment cycles.
* Imaging studies (e.g., bone scans, computed tomography (CT) scans) every two cycles to determine the response to treatment.
* Surgical or medical suppression of testosterone in patients whose cancer cells continue to grow due to exposure to the hormone....

Background:

* Satraplatin is an oral, third-generation platinum analog that has recently been shown to increase prostatic specific antigen (PSA) decline rates and progression-free survival in hormone-resistant prostate cancer.
* Satraplatin acts by binding to deoxyribonucleic acid (DNA) forming intra- and interstrand cross links (DNA adducts), resulting in cell-cycle arrest in G2 phase and eventual apoptosis. One of the mechanisms that bring about resistance to platinum-based chemotherapy is removal of the platinum-DNA adducts by DNA repair pathways, called nucleotide excision repair (NER) and base excision repair (BER) pathways.
* Polymorphisms in the DNA repair genes causing impaired NER and BER capability has recently been shown in some cancers, including head and neck squamous cell carcinoma, non-small cell lung carcinoma, and ovarian carcinoma to predict better treatment outcome and response to platinum treatment.

Objectives:

* Primary objective of this single arm study is to determine if the presence of ERCC1 variant gene polymorphism which is involved with DNA damage repair may be associated with an impact on the progression-free survival of patients with metastatic prostate cancer.
* Secondary objectives of this study includes demonstration of biologic effect by the drug satraplatin in the patient and in the tumor whenever possible, by obtaining tissue biopsy and white blood cell collections, to determine correlation of biologic or clinical effects with PSA progression, evaluate correlations between genotype expression, repair pathways and clinical events, and obtain laboratory correlates which will include pharmacogenetic analysis of prostate cancer patients with genotyping using Polymerase chain reaction (PCR) followed by either restriction fragment length polymorphism or direct sequencing to genotype single nucleotide polymorphisms of ERCC1, x-ray repair cross-complementing protein 1 (XRCC1), and poly (ADP-ribose) polymerase 1 (PARP1).

Eligibility:

* Patients with metastatic androgen-independent prostate cancer.
* Had docetaxel-based chemotherapy, but no more than 1 previous cytotoxic chemotherapy line.
* Good organ function.

Design:

* Phase II trial with single stage design and a planned accrual of 66 patients.
* Progression-free survival will be determined using a Fisher's exact test.
* Will treat all enrolled patients with oral satraplatin 80 mg/m\^2 dose on days 1-5 of every 35-days cycle plus Prednisone 5 mg twice daily every 35 days.
* Genotyping will be performed after the first 20 patients to determine if the proportion for wild-type ERCC1 and variants follow a 20:80 split.

Satraplatin and Prednisone to Treat Prostate Cancer

A Phase II Study of Satraplatin and Prednisone in Metastatic Androgen Independent Prostate Cancer (AIPC)

Time between the start of therapy and progression. Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Progressive Disease is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Overall Survival is the time between the first day of treatment to the day of death.

National Cancer Institute (NCI)

Principal investigator

The time frame for adverse events includes one year follow-up data.

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. William Dahut

24 pts were enrolled but only 21/24 were assessed for OS. One pt died on treatment and (e.g.3 pts were non-evaluable for analysis of response).

Progression Free Survival.

Number of Participants With Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v3.0)

Median Overall Survival (OS)

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

Diseases and Abnormalities at or Before Birth

Blood and Lymph Conditions

Skin and Connective Tissue Diseases

Asthma

Sclerosis

Lung Diseases

Fibrosis

Pulmonary Fibrosis

Cystic Fibrosis

Sarcoidosis

Alpha 1-Antitrypsin Deficiency

Tuberous Sclerosis

Sarcoidosis, Pulmonary

Respiratory Tract Diseases

Hypersensitivity

Pancreatic Diseases

Genetic Diseases, Inborn

Infant, Newborn, Diseases

Lung Diseases, Interstitial

Lymphoproliferative Disorders

Lymphatic Diseases

Hypersensitivity, Delayed

Hamartoma

Neoplasms, Multiple Primary

Neoplastic Syndromes, Hereditary

Congenital Abnormalities

Malformations of Cortical Development

Nervous System Malformations

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Alpha-1 Antitrypsin Deficiency

Tuberous Sclerosis Complex

Vasodilator Agents

Respiratory System Agents

Nitric Oxide

Alpha 1-Antitrypsin

Protein C Inhibitor

Subjects with pulmonary disease or possible pulmonary disease and Relatives

Tatyana Worthy, R.N.

Joel Moss, M.D.

Tatyana Worthy, B.S.

This study is designed to evaluate the genetics involved in the development of lung disease by surveying genes involved in the process of breathing and examining the genes in lung cells of patients with lung disease.

The study will focus on defining the distribution of abnormal genes responsible for processes directly involved in different diseases affecting the lungs of patients and healthy volunteers.

Optional CT Sub-study

The standard CT scan will be compared to the low dose radiation CT scan for the 150 subjects enrolled in the sub-study to assess the variation between the two techniques. Specifically, the quantitative computer aided detection of lung CT abnormalities from LAM can be compared to assess whether low radiation dose CT exams is an alternative to conventional CT to monitor disease

status.

This optional sub-study will be offered to up to 100 adult subjects with lung disease and up to 50 children age 9 and older with CF. Children will not be enrolled in the optional CT sub-study unless they have had a standard CT scan for medical purposes to use in comparison. One additional low dose radiation CT scan of the chest may be done as part of this sub-study when these subjects have their next annual CT scan.

This study is designed to evaluate genetic mechanisms of lung disease by surveying polymorphic genes involved in respiratory function and examining gene expression in the lung cells of individuals with pulmonary disease (e.g., alpha 1-antitrypsin deficiency, asthma, chronic obstructive pulmonary disease, cystic fibrosis, sarcoidosis, history of infection, and genetic mutations consistent with lung pathology). Emphasis will be on defining the distribution of allelic variants of nitric oxide synthase, alpha 1-antitrypsin, and the cystic fibrosis transmembrane conductance regulator genes in patients and in age- and sex-matched healthy individuals in a control population.

Role of Genetic Factors in the Development of Lung Disease

Role of Genetic Factors in the Pathogenesis of Lung Disease

.This is a new requirement and the sharing of IPD is not discussed in the protocol.

distribution of genetic variants of nitric oxide synthases and other candidate genes involved in pulmonary function

The secondary scan can also be used to obtain a detailed assessment of AML-like tumors and lymphangioleiomyomas in the abdomen or pelvis region when they are detected in the standard chest-abdomen-pelvis CT scan. The enhanced resolution is expected to help classify the tumors without the need for invasive biopsy, for example, by detecting traces of fatty tissue in the tumor to confirm the identity of AML.

Suburban Hospital

National Heart, Lung, and Blood Institute (NHLBI)

Musculoskeletal Diseases

Breast Neoplasms

Arthritis

Arthralgia

Joint Diseases

Breast Diseases

Skin Diseases

Pain

Neurologic Manifestations

Letrozole

Anastrozole

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Femara(Letrozole) 2.5mg 1tab qd, Arimidex(Anastrozole) 1mg 1tab qd

Aromatase Inhibitor(Femara or Arimidex)

Eun Sook Lee, MD, PhD

The purpose of this study is to investigate the relationship between the side effects(especially arthralgia and arthritis) which appear in the patients who are prescribed aromatase inhibitor(AI) and the CYP19 genetic polymorphisms.

CYP19 Genetic Polymorphism & Aromatase Inhibitor(AI)

Significance of CYP19 Genetic Polymorphism on Musculoskeletal Symptom & Complication of Aromatase Inhibitor(AI)

Korea University

Korea University Anam Hospital

Eun Sook, Lee

Infections

Hematologic Neoplasms

Communicable Diseases

Mycoses

Invasive Fungal Infections

Aspergillosis

Invasive Pulmonary Aspergillosis

Pulmonary Aspergillosis

Hematologic Diseases

Bacterial Infections

Bacterial Infections and Mycoses

Lung Diseases, Fungal

Anti-Infective Agents

Voriconazole

Clotrimazole

Miconazole

Antifungal Agents

Cytochrome P-450 Enzyme Inhibitors

Cytochrome P-450 CYP3A Inhibitors

Patients with hematologic malignancies who were given voriconazole to treat invasive (pulmonary) aspergillosis at Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

voriconazole

Multiple factors are associated with a large variability in voriconazole exposure following standard dose administration, such as non-linear saturable pharmacokinetics, drug-drug interactions, liver disease, patient age, and genetic polymorphism of the metabolic enzymes.

Voriconazole is extensively metabolized by the human hepatic enzymes, primarily mediated by CYP2C19. The polymorphisms account for a relatively large portion of inter-individual variance observed in voriconazole plasma concentrations.

However, there are limited data on the relationships between voriconazole blood levels and clinical outcomes or safety in Asian populations.

The purpose of this study is to investigate the relationships of voriconazole blood levels with genetic polymorphism, safety, and clinical outcomes in immunocompromised patients with invasive pulmonary aspergillosis.

The investigators are trying to establish that routine clinical practice for voriconazole therapeutic drug monitoring can improve the efficacy and safety outcomes.

In Korean patients with hematologic malignancy, the investigators also want to propose the optimal dosing guideline of voriconazole with different genetic polymorphisms.

* Venous blood sampling will be carried out at steady state for therapeutic drug monitoring(trough sampling:right before the dose)
* Genotyping will be performed using peripheral blood.

Voriconazole Trough Plasma Levels : Genetic Polymorphism, Efficacy, Safety in Patients With Hematologic Malignancy

The Correlation of Voriconazole Trough Plasma Levels With Genetic Polymorphism, Efficacy, and Safety Outcomes in Hematologic Malignancy Patients With Invasive Pulmonary Aspergillosis

Successful outcome = complete response + partial response Unsuccessful outcome = stable disease + failure of therapy + indeterminate response

IFI (invasive fungal infection)-related mortality at 12 weeks

Successful outcomes at 1 week,2 weeks,4 weeks, and 8 weeks after voriconazole use

Non-IFI (invasive fungal infection)-related mortality at 12 weeks

Adverse drug reactions (liver function test impairment, visual disturbance, hallucination, photosensitive rash, renal impairment)

Asan Medical Center

Assistantant Professor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
the Effect of ABCC2 Genetic Polymorphism on Neurotoxicity in Gastrointestinal Cancer Patients Receiving Oxaliplatin	NCT05494320	Gastrointestina...	Folfox Protocol	18 Years -	Ain Shams University
Satraplatin and Prednisone to Treat Prostate Cancer	NCT00634647	Prostate Cancer Genetic Polymor...	Satraplatin prednisone	18 Years -	National Institutes of Health Clinical Center (CC)
Role of Genetic Factors in the Development of Lung Disease	NCT00001532	Cystic Fibrosis Pulmonary Fibro... Tuberous Sclero... Asthma Pulmonary Sarco...		2 Years - 90 Years	National Institutes of Health Clinical Center (CC)
CYP19 Genetic Polymorphism & Aromatase Inhibitor(AI)	NCT00973505	Breast Neoplasm... Arthralgia Arthritis Genetic Polymor...	Aromatase Inhib...	18 Years - 80 Years	Korea University Anam Hospital
Voriconazole Trough Plasma Levels : Genetic Polymorphism, Efficacy, Safety in Patients With Hematologic Malignancy	NCT01148160	Invasive Fungal...	voriconazole	15 Years -	Asan Medical Center

Spots Global Cancer Trial Database for genetic polymorphism