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

Clinical trial: Study of XL647 in Subjects With Non-Small-Cell Lung Cancer

Summary: The purpose of this phase II study is to determine the safety, tolerability, and activity of XL647 in previously untreated subjects with non-small cell lung cancer (NSCLC). XL647 is a small molecule that potently inhibits multiple receptor kinases, including EGFR, VEGFR2 (KDR), ErbB2, and EphB4. Sensitivity to EGFR inhibitors has been linked to specific EGFR mutations and associated with certain clinical characteristics in patients with NSCLC (eg, female, minimal and remote smoking history, and adenocarcinoma histology).


Eligibility: Inclusion Criteria:
  -  Subject has NSCLC with a histologically confirmed diagnosis of adenocarcinoma with measurable disease (stage IIIB, with malignant pleural effusion, and stage IV) and either has a demonstrated activating mutation of the EGF receptor in tumor tissue or meets one of three criteria: asian, female, and minimal or no smoking history.
  -  Measurable disease defined according to RECIST
  -  ECOG performance status of 0 or 1
  -  Normal organ and marrow function
  -  No other malignancies within 5 years, except for non-melanoma skin cancer
  Exclusion Criteria:
  -  Radiation to ≥25% of bone marrow within 30 days of XL647 treatment
  -  Prior systemic anticancer therapy, including cytotoxic chemotherapy, anti-VEGF, anti-VEGFR, or anti-EGFR agents or investigational drug
  -  Subject has not recovered to ≤ grade 1 or to within 10% of baseline values from adverse events due to other medications administered > 30 days before study enrollment
  -  Receiving anticoagulation therapy with warfarin (low-dose warfarin < 1 mg/day, heparin and low molecular weight heparins are permitted)
  -  The subject meets any of the following cardiac criteria:
  -  Corrected QT interval (QTc) of > 460 msec
  -  Family history of congenital long QT syndrome or unexplained sudden death
  -  History of sustained ventricular arrhythmias
  -  Has a finding of left bundle branch block
  -  Has an obligate pacemaker
  -  Has important bradycardia defined as a heart rate of < 50 bpm due to sinus node dysfunction
  -  Has uncontrolled hypertension
  -  Has symptomatic congestive heart failure, unstable angina, or a myocardial infarction within the past 3 months
  -  Has a serum potassium or serum magnesium level that falls outside the normal range
  -  The subject has progressive symptomatic or hemorrhagic brain or leptomeningeal metastases
  -  Uncontrolled intercurrent illness
  -  Subject is pregnant or breastfeeding
  -  Known HIV

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

Clinical trial: Factors Contributing To Cardiovascular Morbidity and Mortality in Patients With Gastrointestinal Bleeding

Summary: The rate of complication and death of patients with acute digestive tract bleeding is increased in the setting of acute coronary heart disease. The aim of the study is to establish the relative importance of the risk factors contributing to the death rate from acute digestive tract bleeding in patients admitted with acute coronary heart disease.

Detailed description: The rate of complication and death of patients with acute digestive tract bleeding is increased in the setting of acute coronary heart disease. The aim of the study is to establish the relative importance of the risk factors contributing to the death rate from acute digestive tract bleeding in patients admitted with acute coronary heart disease. This study will be conducted at MMC and involve collecting your clinical information from our medical records and computer systems. Approximately 200 adult patients with acute coronary heart disease and acute digestive tract bleeding admitted to MMC will be enrolled and followed up for 1 year after recruitment. We propose to develop criteria and a scoring system that will assist your doctors in caring for patients like you in the future.

Eligibility: Inclusion Criteria:
  -  Consecutive patients with acute CS and acute GI bleeding

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

Clinical trial: Effect of Statin Therapy on Disease Progression in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Summary: The purpose of this study is to determine whether the medication pravastatin will ameliorate renal and cardiovascular disease over a 3-year period in children and young adults with autosomal dominant polycystic kidney disease (ADPKD).

Detailed description: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, affecting 1 in 400 to 1000 individuals and accounting for 4% of end-stage renal disease in the United States and 8-10% in Europe. The condition is characterized by progressive development of kidney cysts with kidney enlargement and associated loss of kidney function. High blood pressure and cardiovascular disease are common in patients with ADPKD. Although the condition is often thought to affect primarily adults, it is clear that the disease can be present in the fetus and young children.
  This study was designed to determine if treatment with the medicine pravastatin can slow the progression of kidney and heart disease when initiated early in life in patients with ADPKD. The Investigators will assess differences between pravastatin and placebo study groups over the three-year study period with respect to: 1) total kidney volume as assessed by magnetic resonance imaging (MRI); 2) left ventricular mass index as assessed by MRI; 3) urinary albumin excretion; and 4) endothelial-dependent vasodilation as assessed by brachial ultrasound. A total of 110 subjects were enrolled in this research study. This study involved pediatric subjects because the Investigators believe that early intervention is critical if they are to decrease the morbidity and mortality associated with this condition. If pravastatin is shown to be effective in ameliorating progression of renal and cardiovascular disease in this study, routine management of people with this condition will be drastically altered.

Eligibility: Inclusion Criteria:
  -  Age 8-22 years
  -  Autosomal dominant polycystic kidney disease
  -  Normal kidney function
  Exclusion Criteria:
  -  Abnormal kidney function
  -  Past allergic history to medications used in study
  -  Liver disease
  -  Muscle disease/dystrophy
  -  Pregnancy, planned pregnancy, or lactation within study period
  -  Inability to cooperate with or clinical contraindication for magnetic resonance imaging

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

Clinical trial: Efficacy, Safety, and Tolerability of ACZ885 in Patients With Muckle-Wells Syndrome

Summary: This study is designed to provide efficacy and safety data for ACZ885 (a fully human anti-interleukin-1beta (anti-IL-1beta) monoclonal antibody) administered as an injection subcutaneously (s.c.) in patients with Muckle-Wells Syndrome.
  Part I is an 8-week open-label, active treatment period to identify ACZ885 responders.
  Part II is a double-blind, placebo-controlled period to assess primarily the efficacy of ACZ885 compared to placebo.
  Part III is an open-label, active treatment period where patients will receive ACZ885 every 8 weeks after withdrawal or completion of Part II.


Eligibility: Inclusion Criteria:
  -  Molecular diagnosis of NALP3 mutations and clinical picture resembling Muckle-Wells Syndrome.
  -  Muckle-Wells Syndrome patients who participated in the CACZ885A2102 study, will have the option to participate in this study upon disease flare
  -  Muckle-Wells Syndrome patients requiring medical intervention either untreated or treated (i.e. under ACZ885, anakinra, or any other investigational IL-1 blocking therapy).
  Exclusion Criteria:
  -  History of being immunocompromised, including a positive HIV at screening test result.
  -  No live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose.
  -  History of significant medical conditions, which in the Investigator's opinion would exclude the patient from participating in this trial.
  -  History of recurrent and/or evidence of active bacterial, fungal, or viral infections.
  -  Positive tuberculin skin test at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit, according to national guidelines.
  Other protocol-defined inclusion/exclusion criteria may apply

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

Clinical trial: Hirschsprung Disease Genetic Study

Summary: Hirschsprung disease is a genetic condition caused by lack of nerve cells in varying lengths of the intestines. This study will investigate the complex genetic basis of the disease, which involves multiple interacting genetic factors.

Detailed description: Hirschsprung disease (HSCR) is a birth defect resulting from the absence of nerve (ganglion) cells in the gastrointestinal tract. Hirschsprung disease has a population incidence of 1/5000 live births and most often occurs as an isolated condition. However, approximately 30% of HSCR cases are associated with other birth defects such as Down syndrome, deafness, hypopigmentation, and congenital central hypoventilation syndrome. Hirschsprung disease is a genetic condition with autosomal dominant, autosomal recessive, and multigenic patterns of inheritance described.
  Dr. Aravinda Chakravarti's laboratory has been investigating the genetics of Hirschsprung disease (HSCR) for more than twenty five years. The goal of this research study is to identify genes harboring causative HSCR mutations and to better understand the complex inheritance of HSCR in families by whole genome mapping and sequencing studies. Specifically, the study aims to determine the frequency with which mutations in any human gene lead to familial and isolated forms of HSCR. Further, the study will collect clinical information and investigate possible genotype - phenotype correlations.
  Molecular analysis using markers and sequencing, and statistical analysis of these data will be used to identify regions of human chromosomes where putative HSCR disease genes may be located. In addition, the DNA sequence of known and/or suspected HSCR genes will be assessed in individual patients and their family members, in search of causative HSCR susceptibility variants and variants that may affect presentation of the disease and treatment outcomes. Phenotypic information will include pathology, surgical, and other clinical outcomes related to Hirschsprung disease. This study will hopefully lead to a better understanding of the genetics of HSCR and, further down the road, improved diagnosis, treatment, and genetic counseling.
  This study asks volunteers to:
  1. Complete a medical/family history questionnaire
  2. Provide access to some medical records
  3. Submit blood samples from the individual(s) affected with Hirschsprung disease and his/her parents (if available)

Eligibility: Inclusion Criteria:
  - Individuals with Hirschsprung disease and their first degree relatives (any segment length of disease, with or without other congenital anomalies or health problems, single or multiple affected individuals in family)
  Exclusion Criteria:
  -  Unable or unwilling to provide sample for genetic studies
  -  Individual, parent, or guardian unable to comprehend and provide informed consent

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

Clinical trial: Genetic Polymorphisms Associated With Cigarette Smoking and Risk of Graves’ Disease

Summary: Cigarette smoking is a well-recognized risk factor of Graves’ disease and, particularly, Graves’ ophthalmopathy. Hence, germline polymorphisms of detoxification genes and genes belonging to the major DNA repair/apoptosis pathways might have an important role in disease susceptibility. In addition, as some of these genes are regulated by thyroid hormones, they could affect the outcome of these patients. Our objective was to assess the influence of the GST, CYP and TP53 gene polymorphisms in the risk of Graves' disease and its outcome.

Detailed description: Although the role of many polymorphisms of genes related to toxins’ metabolism has been extensively investigated regarding the susceptibility to thyroid cancer, their influence in thyroid autoimmune diseases risk is still largely unknown. Hence, this study was designed to assess the influence of GSTT1, GSTM1, GSTP1, CYP1A1 and 72TP53 polymorphic inheritance on the susceptibility to Graves' disease and to its response to the treatment.

Eligibility: Inclusion Criteria:
  -  Graves' disease patients

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

Clinical trial: Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer

Summary: The purpose of this study is to try to learn more about how small molecule kinase inhibitors work in treating lung cancer. Some early studies have shown that gefitinib, erlotinib and similar drugs are more likely to work if a particular DNA change (also known as a mutation) is found in a protein that is important in lung cancer. This protein is called the epidermal growth factor receptor (EGFR). Since small molecule kinase inhibitors sometimes stop working, we would like to examine your tumor to learn why these medicines are not working as well. Your tumor will be examined for a variety of things including changes in the DNA of the EGFR. We will also sequence parts of the genes for HER2, HER3, HER4, and KRAS, other proteins thought to be important in lung cancer.

Detailed description: The goal of this protocol is to determine mechanisms of resistance to epidermal growth factor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC). A number of trials have shown small molecule kinase inhibitors to be active agents in the treatment of NSCLC [1]. Clinically these drugs have been noted to produce dramatic but infrequent responses. Mutations in the epidermal growth factor receptor have been shown to correlate with sensitivity to gefitinib and erlotinib[2,3]. However, we know that most patients who have initial responses to EGFR-TKI eventually progress. The mechanism of acquired clinical resistance to these inhibitors in patients incompletely understood.
  This is a protocol to study clinical characteristics and biopsy tissue of patients with non-small cell lung cancer who have had previous clinical response to small molecule kinase inhibitors and subsequently experience progression of disease. The tissues and other specimens will be used to carry out laboratory studies to explore the molecular basis of sensitivity and resistance to small molecule kinase inhibitors.

Eligibility: Inclusion Criteria:
  Patients diagnosed with unresectable or metastatic non-small cell lung cancer (NSCLC) and who fulfill the following eligibility criteria will be considered eligible for this study.
  -  Patient must have previously received treatment with small molecule kinase inhibitors targeting at least, in part, EGFR patients may have received other treatments since treatment with small molecule kinase inhibitors including radiation or chemotherapy)
  -  Development of disease progression while actively receiving tyrosine kinase inhibitor
  -  Signed informed consent
  Exclusion Criteria:
  -  None

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

Clinical trial: Clinical Outcomes in Hereditary Cancer

Summary: Compare the clinical characteristics and post-surgical outcomes (overall survival)of pancreatic cancer patients of Ashkenazi descent with or without germline founder mutations in BRCA1 or BRCA2 .
  Compare the clinical characteristics and outcomes (time to progression) of breast cancer patients of Ashkenazi descent with or without germline founder mutations in BRCA1 or BRCA2 receiving paclitaxel chemotherapy for metastatic disease.

Detailed description: Compare the clinical characteristics and post-surgical outcomes (overall survival)of pancreatic cancer patients of Ashkenazi descent with or without germline founder mutations in BRCA1 or BRCA2 .
  Compare the clinical characteristics and outcomes (time to progression) of breast cancer patients of Ashkenazi descent with or without germline founder mutations in BRCA1 or BRCA2 receiving paclitaxel chemotherapy for metastatic disease.

Eligibility: Inclusion Criteria:
  -  Included in DB0363-03
  -  Jewish religious preference at registration
  -  Archival material available for testing
  -  Adequate post-surgical follow-up
  -  Jewish religious preference at registration
  -  Archival material available for testing
  -  Adequate follow-up to determine time to progression
  Exclusion Criteria:
  -Subjects will not be included in the analyses if a DNA sample cannot be obtained.

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

Clinical trial: Chemotherapy Resistance in Osteogenic Sarcoma and Other Solid Tumors

Summary: The purpose of this study is to investigate tumors in the laboratory to determine how and why they respond, or fail to respond to different drug therapies. This study will also investigate why high pressure develops within tumors and how this affects how well drugs work. We will also take blood samples before and/or after your procedure to measure biochemical factors that may help us predict the behavior of osteogenic sarcoma and other solid tumors.

Detailed description: When tumor tissue known or presumed to be a primary or secondary bone cancer or solid tumor with known elevated intra-tumoral pressure such as retinoblastoma is being removed or has been removed for diagnostic or therapeutic reasons a small sample of it will be obtained for this study. The tumor samples will be used to study in vitro, determinants of chemotherapy resistance and oncogenesis. These determinants will be correlated with histologic response to preoperative chemotherapy and clinical outcome (event free survival). In addition, blood samples (20ml) may be obtained before or after the procedure.

Eligibility: Inclusion Criteria:
  -  All patients with a presumed or known diagnosis of a primary or secondary bone cancer or other solid tumor who are having or have had a biopsy or surgery to remove tumor for diagnostic or therapeutic reasons. No tumors will be obtained solely for research purposes.
  -  All adult patients (> or = to 18 yrs.) will have given written informed consent.
  -  All minor patients (<18 yrs.) will have given assent to the best of their ability to understand, and their parent or guardian will have given written informed consent
  Exclusion Criteria:
  -  N/A

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

Clinical trial: Anonymous Testing of Pathology Specimens for BRCA Mutations in Ashkenazi Jewish Individuals Who Have Cancer

Summary: The intent of the proposed study is to describe the prevalence of the most common recurring mutations in BRCA1 and BRCA2, blmAsh , and the A636P MSH2 mutation among Ashkenazi Jewish individuals with a variety of cancer diagnoses. If a substantial proportion of these samples contain such mutations, future patients presenting with these diseases may wish to undergo genetic counseling and, if appropriate, formal genetic testing. The benefit from such a process would pertain mainly to the families of these individuals.

Detailed description: Germline mutations in the genes BRCA1 and BRCA2 have been demonstrated in the majority of hereditary breast and ovarian cancer families. The increased risk to develop both breast and ovarian cancer associated with inheriting a BRCA1 or BRCA2 mutation has been well established. It has also been suggested that is an overrepresentation of other cancers such as colon, prostate and pancreatic cancer present in BRCA1 or BRCA2 families. Population specific mutations in BRCA1 and BRCA2 have been identified. In the Ashkenazi Jewish population, 3 specific mutations have been seen in 2% of the population. This study will anonymously screen archived tissue samples of Ashkenazi Jewish individuals diagnosed with cancer between 1993 and 1996 at MSKCC for the three founder mutations seen in the Ashkenazi Jewish population. Results will be stratified by tumor type and compared with the population frequency to determine whether individuals inheriting mutations in BRCA1 or BRCA2 may have an increased risk to develop other cancers, in addition to breast and ovarian cancer. This information will be useful in helping to identify individuals who may benefit from genetic counseling and possibly genetic testing who to date are not typically referred. It will also be useful in developing high-risk cancer screening strategies and determining appropriate options for prophylactic surgery.

Eligibility: Inclusion Criteria:
  -  Diagnosis of cancer made at MSKCC or collaborating institutions, AND
  -  Tissue block of tumor or normal margin or extracted DNA available for study and sufficient material present to allow study without exhausting block or DNA,
  -  Individual self-identified as Jewish on intake.

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

Clinical trial: Molecular Markers in Treatment in Endometrial Cancer

Summary: The purpose of this prospective multicenter trial is to investigate the value of molecular markers in endometrial cancer for predicting lymph node metastasis and prognosis in relation to treatment.

Detailed description: This is a prospective multicenter study to investigate the predictive value of molecular markers in endometrial cancer for lymph node metastasis, prognosis and treatment. For the previously studied tumor markers p53, p16, ER, PR and HER2neu, we want to investigate the expression in curettage material in relation to lymph node metastasis and prognosis among endometrial carcinoma patients. We also want to investigate the distribution of genetic alterations in fresh frozen tumor tissue in order to design prospective randomized treatment trials of metastatic endometrial cancer based on molecular profile. There will be a special emphasis on disturbances in the pathways influenced by new targeted therapy, such as inhibitors of Her2/NEU, EGFR, receptor tyrosine kinase, mTOR, PTEN and hormone receptor pathways.

Eligibility: Inclusion Criteria:
  -  Women with endometrial carcinoma
  -  Available endometrial biopsy
  -  Informed consent
  Exclusion Criteria:
  -  No informed consent

Relevance to patient case: not relevant