araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH)

Summary: This study is designed to better understand the molecular biology of paroxysmal nocturnal hemoglobinuria (PNH) and to determine if prion protein (PrP) functions in long term hematopoietic stem cell renewal.

Detailed description: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolytic anemia, thrombosis, and variable cytopenia. It can be associated with significant morbidity including acute kidney failure, cerebral infarction, mesenteric infarction, Budd-Chiari syndrome, aplastic anemia, and leukemic transformation. The average survival time from diagnosis is 15 years.
  PNH is an acquired clonal disorder of the hematopoietic stem cell. Two distinct populations of hematopoietic cells exist in each PNH patient: one non-clonal population of normal cells, and one clonal population of PNH cells. The clonal population of PNH cells is identified by a mutation in the PIG-A gene that results in absence of the glycophosphatidylinositol (GPI) anchor of several surface proteins. Consequently, these surface proteins are unable to perform their functions on the cell surface. Deficiency of two of these surface proteins, CD55 (decay accelerating factor) and CD59 (membrane inhibitor of reactive lysis) that prevent complement mediated destruction, have been shown to underlie the clinical presentation of PNH. Identifying the mutation causing the predominant clones may help us better understand the molecular biology of PNH. When this is accomplished, new therapies to control and eventually cure the disease can be designed.
  In addition, we propose to determine the function of PrP in human hematopoietic stem cells. PrP is a glycoprotein attached to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. In PNH, a disorder whose pathogenesis lies in the absence of GPI anchors, PrP expression is reduced in monocytes and granulocytes from the PNH clone.

Eligibility: Inclusion Criteria:
  1. Subjects suspected of or diagnosed with Paroxysmal Nocturnal Hemoglobinuria (PNH)
  2. Age > 7
  Exclusion Criteria:
  1. Those not meeting the inclusion criteria

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) [Extension of Study 156-04-001]

Summary: Investigation into the long-term safety and efficacy of OPC-41061 in repeated oral administrations at doses of 15 mg twice daily in patients with ADPKD who completed the preceding dose-finding study (156-04-001).

Detailed description: Investigation into the long-term safety and efficacy of OPC-41061 in repeated oral administrations at doses of 15 mg twice daily in patients with ADPKD who completed the preceding dose-finding study (156-04-001).

Eligibility: Inclusion Criteria:
  -  Patients who completed 5-day repeated administrations and the follow-up observation in the preceding study (156-04-001)
  -  Patients in whom the safety of repeated administration was confirmed based on the investigator's reports from the preceding study (156-04-001)
  Exclusion Criteria:
  -  Patients with serum creatinine concentration of 2.5 mg/dL or higher at the screening examination
  -  Patients with any of the following complications
  -  Uncontrolled hypertension
  -  Serious cardiovascular disease (eg. heart failure) or hepatic disease (eg. cirrhosis)"
  -  Patients with any of the following complications or history thereof
  -  Clinically significant drug allergies (anaphylaxis) or hypersensitivity (especially, hypersensitivity to benzazepine derivatives or suspected hypersensitivity thereto)
  -  Inability to personally give consent due to a mental disease "
  -  Patients with SBP (in sitting position) <90 mm Hg (at screening examination)
  -  Patients with history of massive bleeding or bleeding tendency
  -  Patients with a history of drug or alcohol abuse within 6 months prior to the screening examination
  -  Pregnant women, lactating women, or women who may become or plan to become pregnant
  -  Patients who received any investigational drug other than OPC-41061 within 30 days prior to commencement of administration of OPC-41061
  -  Any patient who, in the opinion of the principle investigator or attending investigators, should not participate in the study

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Identifying Early Lung Cancer Cells in Malignant Pleural Effusion Samples From Patients With Primary Lung Cancer

Summary: RATIONALE: Studying samples of pleural fluid in the laboratory from patients with lung cancer may help doctors identify early lung cancer cells. It may also help the study of lung cancer in the future.
  PURPOSE: This laboratory study is looking at malignant pleural effusion samples from patients with primary lung cancer to see if early lung cancer cells can be identified.

Detailed description: OBJECTIVES:
  -  Isolate and identify lung cancer precursor cells in discarded pleural fluid specimens obtained during routine thoracentesis procedures for the diagnosis and treatment of malignant pleural effusions.
  OUTLINE: Malignant pleural effusion specimens obtained from the Pathology Department at the University Hospitals of Cleveland are analyzed using an immunomagnetic bead enrichment assay to isolate cells of epithelial origin. The isolated cells are then stained with fluorescent DNA binding dye, Hoechst 33342, and other markers (i.e., CD133, CD24/CD44) and sorted by flow cytometry into progenitor and nonprogenitor subpopulations. The sorted subpopulations are separated and examined functionally by in vitro and in vivo studies. Sphere culture studies are also performed on the sorted subpopulations. The specimens may also be utilized for transcriptional profiling studies, RNAi studies, and for the establishment of long-term cultures and cell lines. DNA is also isolated and stored from tumor and nonepithelial normal cell compartments for future genetic studies on known and unidentified genetic abnormalities contributing to the development of lung cancer, such as EGFR, ErbB2, K-ras, and p53 mutational status.

Eligibility: DISEASE CHARACTERISTICS:
  -  Cytologically positive malignant pleural effusion secondary to primary small cell or non-small cell lung cancer
  -  Recruited from the Division of Hematology/Oncology, the Multidisciplinary Thoracic Oncology Group of Ireland Cancer Center, or the inpatient or outpatient units of Case Medical Center-University Hospitals
  PATIENT CHARACTERISTICS:
  -  Not specified
  PRIOR CONCURRENT THERAPY:
  -  Not specified

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Cancer Risk in Organ Transplant Recipients and End-Stage Renal Disease

Summary: Background:
  -  Solid organ transplantation provides life-saving treatment for end-stage organ disease but is associated with an increased cancer risk because of the need for long-term immunosuppression
  -  End-stage renal disease (ESRD), the most common type of end-stage organ disease leading to transplant, is itself linked to increased risk for some cancers
  -  The role of immunosuppression and other factors causing cancer in this setting are not fully understood.
  Objectives:
  -  To characterize cancer risk in transplant recipients and identify risk factors.
  -  To characterize risk for transmission of cancer from organ donors to recipients.
  -  To describe cancer risk in ESRD.
  Eligibility: Patients are not required for this study. Data are gathered from existing databases of ESRD patients, organ transplant patients and cancer registries.
  Design:
  -  Databases of 1) U.S. transplant recipients, donors and wait list candidates and 2) U.S. ESRD patients will be linked to multiple U.S. cancer registries to identify cancers in transplant recipients and ESRD patients.
  -  The spectrum of cancer risk in transplant recipients and ESRD patients will be evaluated in detail.
  -  The cancer risk in transplant recipients will be examined in relation to whether the donors had cancer.
  -  The proposed cancer risk factors (e.g., underlying medical condition, infection with cancer-causing viruses, immunosuppressive medications) documented in transplant and ESRD files will be studied for association with increased risk of particular types of cancer.

Detailed description: Solid organ transplantation provides life-saving treatment for end-stage organ disease but is associated with substantially elevated cancer risk, largely due to the need to maintain long-term immunosuppression. Despite previous research, important research questions remain concerning the role of immunosuppression and other factors in causing cancer in the setting. Staff at two federal agencies, the National Cancer Institute (NCI) and the Health Resources and Services Administration (HRSA), will link a database containing information on U.S. transplant recipients, wait list candidates, and donors to multiple U.S. cancer registries. These data will be used to conduct research concerning the spectrum of cancer risk in transplant recipients. The data will also be used by HRSA in its public health role overseeing the U.S. solid organ transplant network to maintain and improve safety of organ transplantation.

Eligibility: -  This study will include as subjects all individuals included in the transplant data set. All U.S. solid organ transplant recipients, candidates for transplant, and living related donors.
  In addition, the study will include all individuals in the U.S. ESRD data set.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Study of Tissue and Blood Samples From Patients With Low-Grade Glioma

Summary: RATIONALE: Studying samples of tumor tissue and blood from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment.
  PURPOSE: This research study is looking at tissue and blood samples from patients with low-grade glioma.

Detailed description: OBJECTIVES:
  -  Evaluate the diagnostic and prognostic relevance of alterations of specific chromosomes and chromosomal regions including 7, 9p, 10p, 10q, 13q, 17p, 17q, 19q, 22q, X, and Y, using PCR analysis of microsatellite repeats and FISH.
  -  Evaluate the diagnostic and prognostic relevance of DNA ploidy by flow cytometric analysis; compare with ploidy determination by FISH.
  -  Assess the diagnostic and prognostic relevance of various markers of cellular proliferation and cellular function including flow cytometric determination of %S-phase, %G2M, and immunohistochemical evaluation of PCNA, Ki-67, and p53.

Eligibility: 1. Paraffin-embedded tumor tissue blocks of patients enrolled in NCCTG 86-72-51 or 93-72-02 and who had the diagnosis of low-grade glioma.
  2. Patients who have the diagnosis of low-grade glioma with an available paraffin- embedded tumor tissue block enrolled in prospective NCCTG and Mayo studies.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Phase III Trial to Evaluate the Elortinib vs Gefitinib in Advanced NSCLC With EGFR Exon 19 or 21 Mutations

Summary: This is a randomized controlled trial to compare efficacy and safety between erlotinib and gefitinib in advanced NSCLC harboring EGFR exon 19 or 21 mutations.Eligible patients were randomized to receive erlotinib or gefitinib in any line settings.The primary endpoint was progression-free survival (PFS).

Detailed description: Patients with stage IV NSCLC who have EGFR exon 19 or 21 mutations will randomized to received oral erlotinib 150mg or gefitinib 250mg once daily until disease progression or unacceptable toxicity. Method of direct DNA sequencing of tumor tissue is used to analysis EGFR mutation status of exons 18-21. The response will be evaluated by RECIST criteria first month,second month and then repeat every 3 months after the beginning of the treatment weeks.

Eligibility: Inclusion Criteria:
  -  Histologically or cytologically confirmed stage IIIB (wet) or IV NSCLC.
  -  Patients with positive EGFR exon19 or exon21 mutation as confirmed by direct sequencing histologically.
  -  Signing the informed consent form.
  -  The vital organ functions are tolerant to therapy.
  -  Have recovered to CTCAE2 grade below from toxicity of previous chemotherapy and radiotherapy
  -  PS 0-2 scores.
  -  Functional reserve of bone marrow is adequate, e.g. white blood cell count ≥3.0×109/L, planet count ≥90×109/L, and HB≥80×109/L.
  -  Serum bilirubin is 2 times less than the upper limit of normal (ULN), ALT and AST are 3 times less than ULN; for liver metastases, ALT and AST need to be 5 times less than ULN; creatinine should be 2 times less than ULN.
  Exclusion Criteria:
  -  Informed consent is not provided.
  -  Women of pregnancy or breastfeeding.
  -  Have difficulty in swallowing.

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Study To Investigate the Feasibility and Safety of A Dedicated High Resolution Nuclear Breast Imaging Camera

Summary: To evaluate the feasibility, acceptability and safety of using a molecular breast imaging (MBI) Gamma Camera in women at high risk of developing breast cancer


Eligibility: Inclusion Criteria:
  -  Females ≥18 years of age
  -  Undergoing annual breast MRI because of a high risk of breast cancer due to any of the following:
  -  Known BRCA1 or BRCA2 mutation carriers, or is untested for BRCA but is a first degree relative of a BRCA mutation carrier
  -  History of radiation to the chest between 10-30 years of age (e.g. Hodgkin's Disease)
  -  History of Cowdens or Li Fraumeni Syndrome
  -  A first degree relative with Cowdens or Li Fraumeni Syndrome
  -  Prior breast biopsy positive for lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia or atypical ductal hyperplasia (ADH)
  -  Family history consistent with a hereditary breast cancer syndrome and estimated personal lifetime cancer risk ≥25% using the IBIS risk evaluator
  Exclusion Criteria:
  -  Pregnant or lactating
  -  History of invasive breast cancer or ductal carcinoma in situ (DCIS)
  -  Unable to undergo MRI because of:
  -  Renal dysfunction with an estimated creatinine clearance of < 30 ml/min calculated using the Cockcroft-Gault formula
  -  Implanted ferrous metal prostheses
  -  Claustrophobia
  -  Medical or psychological conditions that on assessment, make them unable to complete the procedure
  -  Known allergies to Gadolinium-DTPA
  -  Known allergies to Sestamibi (Miraluma or Cardiolite)
  -  Prior bilateral mastectomy
  -  Prior breast biopsy or surgery within 3 months

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Efficacy of Riluzole in Hereditary Cerebellar Ataxia

Summary: The hereditary cerebellar ataxias include diverse neurodegenerative disorders. Hereditary ataxias can be divided into autosomal dominant ataxias (ADCAs), autosomal recessive ataxias (ARCAs), X-linked, and mitochondrial ataxias on the basis of mode of inheritance. The key feature in all these disorders is ataxia typically characterised by poor balance, hand incoordination, postural or kinetic tremor, dysarthria and dysphagia.
  To date no treatment has been shown to slow progression of the disease and symptomatic therapies are limited to few options that are partially effective.
  Purkinje cells project inhibitory signals to the deep cerebellar nuclei(DCN) which have a critical role in cerebellar function and motor performance. DCN neurons fire spontaneously in the absence of synaptic input from Purkinje neurons and modulation of the DCN response by Purkinje input is believed to be responsible for coordination of movement, while uncontrolled spontaneous firing of DCN neurons may underlay cerebellar ataxia. Recent studies have demonstrated that small-conductance calcium-activated potassium (SK) channels inhibitor are able to increase DCN firing rate. Since SK channels are critical regulators of DCN firing rate, SK openers such as the drug riluzole may reduce neuronal hyperexcitability and thereby be useful in the therapy of cerebellar ataxia.
  On this base the investigators published a pilot study in patients with chronic cerebellar ataxia (Ristori et al., Neurology 2010) investigating safety and efficacy of riluzole or placebo administration for 8 weeks. The results demonstrated a significative improvement in International Cooperative Ataxia Rating Scale (ICARS) global score after four weeks and after 8 weeks in the riluzole arm.
  The present protocol is aimed at verifying the safety and efficacy of riluzole administration for a longer period, in a larger sample size of patients, with more stringent diagnostic criteria (hereditary cerebellar ataxia), respect to the above pilot study. Sixty patients will be enrolled in a double-blind, placebo-controlled trial. By central randomisation, patients will take 50 mg of riluzole or placebo twice daily for 12 months. Treatment effects will be assessed by comparing the Scale for the Assessment and Rating of Ataxia (SARA) before treatment and during therapy at months 3 and 12.


Eligibility: Inclusion Criteria:
  -  Patients with genetically confirmed diagnosis of hereditary cerebellar ataxia
  Exclusion Criteria:
  -  Concomitant experimental therapy for ataxia
  -  Serious systemic illnesses
  -  Pregnancy

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: An Observational Study to Evaluate the Safety and Efficacy of FOLFIRI / FOLFOX Plus Cetuximab as First-line Therapy in Patients With KRAS Wild-type Metastatic Colorectal Cancer

Summary: This is an open-label, non-randomized, prospective, multicentric, Phase IV study evaluating FOLFIRI/ FOLFOX plus cetuximab in the first-line therapy of subjects with KRAS wild-type metastatic CRC.

Detailed description: Cetuximab, a chimeric immunoglobulin G1 (IgG1) monoclonal antibody, has been found to potentiate the effects of chemotherapy and radiotherapy in experimental systems. The findings from clinical trials suggest a favorable risk-benefit ratio of the combination of irinotecan or oxaliplatin, infusional 5-FU/FA and biweekly cetuximab, and support the current study to demonstrate the therapeutic value of the biweekly cetuximab regimen as a combination partner for those regimens in subjects with KRAS wild-type mCRC in the first-line setting. The purpose of this study is to generate post marketing surveillance (PMS) data for cetuximab in first-line mCRC, which is mandated by the Licensing Authorities.
  This is an open-label, non-randomized, prospective, multicentric Phase IV study evaluating FOLFIRI/ FOLFOX plus cetuximab in the first-line therapy of subjects with KRAS wild-type metastatic CRC. The study plans to enroll 100 subjects with KRAS wild type CRC at 20 centres across India. Tumour status, physical and laboratory examinations will be performed during the baseline visit. Subjects will be administered FOLFIRI/ FOLFOX and cetuximab according to the clinical condition in the following treatment visits. Regular safety assessments and all adverse events (AEs) will be documented throughout and until the end-of-study visit. The outcome of AEs ongoing at the final tumour assessment visit will be followed up at the end-of-study visit (If possible, 6 weeks after the last administration of study medication but before second-line anticancer treatment, and not earlier than 30 days after the end of study treatment). Skin toxicity present at the end-of-study visit will be followed up until outcome is known.
  OBJECTIVES
  Primary Objective:
  -  To evaluate the safety and tolerability of Cetuximab in combination with standard chemotherapy such as FOLFOX or FOLFIRI as first-line therapy of patients with KRAS wild-type metastatic colorectal cancer.
  Secondary Objective:
  -  To evaluate the efficacy of Cetuximab in combination with standard chemotherapy as first-line therapy of patients with KRAS wild-type metastatic colorectal cancer.

Eligibility: Inclusion Criteria:
  -  Subjects with histologically confirmed, adenocarcinoma of the colon or rectum (mCRC)
  -  Subjects with KRAS wild-type status of tumour tissue
  -  Chemotherapy naïve subjects
  -  Subject who have signed written informed consent (as per institutional protocol)
  Exclusion Criteria:
  -  As per summary of product characteristics of cetuximab

Relevance to patient case: not relevant
Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Non Small Cell Lung Cancer Evaluation According to Pre-determined Drug-targeting Tumor Markers

Summary: Evaluate chemotherapy related tumor markers on non small cell lung cancer by fluorescent in situ hybridization and immunohistochemistry, targets to be studied include EGFR, c-MET, topoisomerase II, p53, topoisomerase I, thymidylate synthase, ERCC1, tau, c-myc, RRM1, class III tubulin. These targets have been chosen because they are targets for chemotherapeutic agents that are currently used in clinical management of these diseases. In total 50 specimen will be studied, approximately one third have mutations/deletions of the EGFR gene.To attempt to establish a correlation between the pre-selected tumor markers and response to chemotherapy, and thus to be able to create a clinically useful classification that would provide clinical guidance for selection of the most effective chemotherapy for a individual patient, and thus be able to logically design more effective clinical trials for the future.


Eligibility: Inclusion Criteria:
  -  Patients with histologically confirmed lung cancer who received standard platinum-containing doublet chemotherapy followed by EGFR tyrosine kinase inhibitors.
  Exclusion Criteria:
  -  non

Relevance to patient case: not relevant