araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)

Summary: The purpose of this signal seeking study is to determine whether treatment with LEE011 demonstrates sufficient efficacy in CDK4/6 pathway activated solid tumors and/or hematologic malignancies to warrant further study.


Eligibility: Inclusion Criteria:
  -  Patient has a confirmed diagnosis of a select solid tumor (except breast cancer (however, triple negative will be included), liposarcoma, CRPC, melanoma and teratoma) or hematological malignancy (except mantle cell lymphoma).
  -  Patient must have been pre-identified as having a tumor with CDK4 amplification or mutation, CDK6 amplification or mutation, Cyclin D1 (CCND1) amplification, Cyclin D3 (CCND3) amplification, or p16 (CDKN2A) mutation
  -  Patient has received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.
  -  Patient has progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines.
  -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  Exclusion Criteria:
  -  Patients has received prior treatment with LEE011.
  -  Patient has clinically significant resting bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval > 109 msec, or QTcF > 450 msec.
  -  Patients has primary CNS tumor or CNS tumor involvement
  -  Patient has received chemotherapy or anticancer therapy ≤ 4 weeks prior to starting study drug

Relevance to patient case: not relevant
Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

Summary: This pilot clinical trial studies gallium Ga 68-edotreotide (68Ga-DOTATOC) positron emission tomography (PET)/computed tomography (CT) in finding brain tumors in younger patients. Diagnostic procedures, such as gallium Ga 68-edotreotide PET/CT imaging, may help find and diagnose brain tumors.

Detailed description: PRIMARY OBJECTIVES:
  I. To determine if 68Ga-DOTATOC (gallium Ga 68-edotreotide) PET when combined with magnetic resonance imaging (MRI) will differentiate embryonal tumors such as medulloblastoma and supratentorial primitive neuroectodermal tumor (PNET) from the low and high grade gliomas.
  II. To determine if 68Ga-DOTATOC PET will aid in the identification of residual tumor post operatively in those patients who were 68Ga-DOTATOC PET positive prior to surgery.
  OUTLINE:
  Patients undergo gallium Ga 68-edotreotide PET/CT at baseline and 1-30 days after surgery.

Eligibility: Inclusion Criteria:
  -  Patients presenting with brain tumors will be eligible for this study
  -  Eligible subjects must be able and willing to undergo the procedures of the study
  -  Electronic version of pre-surgery MRI must be available for co-registration purposes
  -  Fresh frozen tumor, and/or paraffin block of biopsy or resected tumor is recommended, but not required to determine expression of somatostatin receptors in tumor by immunohistochemistry and/or quantitative polymerase chain reaction (qPCR)
  Exclusion Criteria:
  -  Women who are pregnant or breastfeeding
  -  Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin of body that would preclude obtaining an MRI as part of the initial study evaluation
  -  Inability to complete the needed investigational and standard-of-care imaging examinations due to other reasons
  -  Presence of any additional medical condition such as inter-current illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance

Relevance to patient case: not relevant
Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: DNX-2401 With Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma Brain Tumors

Summary: Glioblastoma (GBM) and gliosarcoma (GS) are the most common and aggressive forms of malignant primary brain tumor in adults and can be resistant to conventional therapies. The purpose of this Phase Ib study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor responds to one injection of DNX-2401, a genetically modified, conditionally replicative and oncolytic human-derived adenovirus. DNX-2401 is delivered directly into the tumor where it may establish an active infection by replicating in and killing tumor cells.

Detailed description: Enrollment has been completed for the randomized portion of the study with ongoing evaluation of tumor response and safety. No additional subjects will be randomized or receive interferon gamma (IFN-γ).
  The non-randomized portion of the study is open for screening and enrollment. Eligible subjects will receive a single intratumoral injection of DNX-2401 into a recurrent glioblastoma or gliosarcoma brain tumor using the Alcyone MEMS Cannula (AMC™) System (cannula). Tumor response and safety will be evaluated.
  After receiving DNX-2401, subjects will return to the clinic for study visits at regular intervals for safety monitoring, MRI scans and other assessments for up to 18 months. Thereafter, they will be followed closely for safety and survival.

Eligibility: Inclusion Criteria:
  -  Glioblastoma or gliosarcoma in first or second recurrence only
  -  Documented tumor recurrence or progression after failing prior surgical resection, chemotherapy, or radiation
  -  Tumor size greater than or equal to 1.0 cm in two perpendicular diameters
  -  Not undergoing surgical resection or for whom gross total resection is not possible
  -  Karnofsky Performance Status greater than or equal to 70%
  Exclusion Criteria:
  -  Multiple intracranial malignant glioma lesions
  -  Tumor location or involvement that would result in risk of ventricular penetration during tumor injection
  -  Tumor involving both hemispheres or that which involves the subependyma or suspected cerebrospinal fluid dissemination
  -  Tumor involving brain stem
  -  Documented extracranial metastasis
  -  Inability to undergo MRI
  -  Pregnant or nursing females
  -  Any medical condition that precludes the surgery necessary to administer DNX-2401 into the tumor using the cannula
  -  Immunocompromised subjects or those with autoimmune conditions, active hepatitis or positive for human immunodeficiency virus (HIV)
  -  Li-Fraumeni Syndrome
  Other protocol-defined inclusion/exclusion criteria may apply as outlined in the relevant protocol version

Relevance to patient case: not relevant
Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: Phase I-II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation and Pharmacokinetics of PD-0332991 in Patients Suffering Metastatic Melanoma

Summary: An open label multicentre, phase I-II study with tumour molecular pharmacodynamics (MPD) evaluation and pharmacokinetics of PD-0332991 added to vemurafenib in patients suffering metastatic melanoma with BR.
  The main objective is to establish the Maximum Tolerated Dose (MTD) of PD-0332991 when added to standard vemurafenib therapy (960 mg BID). The estimated MTD is defined as the dose of PD-0332991 combined with vemurafenib that will be associated with a prespecified proportion of patients experiencing a Dose-Limiting Toxicity (DLT), ie, 1/3.


Eligibility: Inclusion Criteria:
  -  Age > 18 years
  -  Stage IV or un-resectable stage III melanoma
  -  Presence of BRAF V600E/K mutation and CDNKN2A loss and expression of Rb using immunohistochemistry in a recent metastatic sample (< 6 months)
  -  A previous exposure to BRAF inhibitor or combination of BRAF and MEK inhibitors therapy is allowed unless it has been stopped more than 3 months before study enrolment(This will defined the two strata of the trial)
  -  No previous therapy by MEK inhibitor unless associated with BRAF inhibitors
  -  No previous therapy with the AKT/PI3K pathway inhibitor
  -  Patients should have a tumour available for repeated biopsies for pharmacodynamics evaluation
  -  Life expectancy of > 3 months
  -  ECOG performance status <2
  -  Signed informed consent
  -  Patient with health insurance coverage
  -  No patient under guardianship or curators
  Exclusion Criteria:
  -  Inadequate hepatic function defined as serum bilirubin>25 μmol/l, transaminases > 3.0 times the upper limit of normal (ULN) or 5ULN in cases of liver metastases;
  -  Inadequate bone marrow function defined as absolute neutrophil count<1500/mcl, platelets<150000/mcl and haemoglobin<8g/dL
  -  Inadequate renal function with serum creatinine>2.0mg/dl) and /or creatinine clearance< 60 ml/min
  -  Untreated brain metastases : Patients with brain metastases will be eligible if they have completed treatment 1 months prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 5 days, and are neurologically asymptomatic
  -  Myocardial infarct or unstable angina within the past 6 months
  -  Concomitant take of drugs known to be strong inhibitor or inducers of CYP314
  -  HIV positive.
  -  Chemotherapy, immunotherapy within 4 weeks
  -  Drugs interfering with PD-0332991 and vemurafenib metabolism
  -  Malabsorption syndrome or other condition that would interfere with enteral absorption
  -  Congenital long QT syndrome or screening QTc > 470 msec
  -  Need for chronic corticosteroid therapy of ≥10 mg of prednisone per day

Relevance to patient case: not relevant
Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: Study of Efficacy and Safety in Premenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer

Summary: This is a multi-center, randomized, double-blinded, placebo controlled trial in pre-menopausal women with advanced breast cancer.

Detailed description: The purpose of this study is to assess the efficacy of LEE011, as measured by progression free survival (PFS), in premenopausal women with HR positive, HER2 negative advanced breast cancer

Eligibility: Inclusion Criteria:
  -  Patient has advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy
  -  Patient is premenopausal or perimenopausal at the time of study entry
  -  Patients who received (neo) adjuvant therapy for breast cancer are eligible
  -  Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer
  -  Patient has HER2-negative breast cancer
  -  Patient must have either measurable disease or If no measurable disease is present, then at least one predominantly lytic bone lesion
  -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  -  Patient has adequate bone marrow and organ function
  Exclusion Criteria:
  -  Patient who has received a prior CDK4/6 inhibitor
  -  Patient is postmenopausal
  -  Patients who currently have inflammatory breast cancer at screening.
  -  Patients who received any prior hormonal anti-cancer therapy for advanced breast cancer, except for ≤ 14 days of tamoxifen or NSAI ± goserelin for advanced breast cancer prior to randomization.
  -  Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated basal cell skin carcinoma, squamous cell skin carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
  -  Patient with CNS metastases.
  -  Patient has active cardiac disease or a history of cardiac dysfunction
  -  Patient is currently using other antineoplastic agents
  -  Patient is pregnant or nursing or physiologically capable of becoming pregnant and not using highly effective contraception

Relevance to patient case: not relevant
Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: Identifying Mechanisms of Resistance to mTOR Inhibitors in Cancer

Summary: mTOR kinase is part of the mTORC1 complex that promotes cap-dependent protein translation, and part of the mTORC2 complex that activates AKT. Everolimus (Afinitor) is an allosteric inhibitor of mTOR that suppresses mTORC1 activity. Everolimus is FDA-approved for the treatment of ER+/HER2- breast cancer (in combination with exemestane), renal cell carcinoma, subependymal giant cell astrocytoma (SEGA), and neuroendocrine tumors of pancreatic origin (PNET), and is currently being tested in ongoing clinical studies in other indications. While everolimus-based therapies elicit anti-cancer effects, most cancers ultimately progress and exhibit everolimus resistance. This study will evaluate genetic mechanisms of resistance to everolimus.


Eligibility: Inclusion Criteria:
  1. Treatment with everolimus (as a single-agent or in combination) for any malignancy for ≥3 months.
  2. A- Patients who are scheduled to undergo a clinically indicated tumor biopsy (as standard of care, or as part of another study) within 5 years following cancer progression on everolimus are eligible.
  B- Patients who already had such a biopsy procedure performed are eligible. Tumors biopsied shortly after progression on everolimus are strongly preferred.
  3. Excess tumor tissue from biopsy must be available for molecular analysis. This will include tumor tissue sufficient to make ≥5 five-micron sections; more tumor tissue is preferred.
  4. Patients currently seen at Dartmouth-Hitchcock Medical Center must be capable and willing to provide informed written consent for study participation. Patients who are no longer seen at DHMC will not be consented for use of archived tissues and data.
  5. For patients currently seen at Dartmouth-Hitchcock Medical Center, patients must be willing to provide an extra 10-20 mL of blood during a routine, clinically indicated blood draw procedure.
  Exclusion Criteria:

Relevance to patient case: not relevant
Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: Image-derived Prediction of Response to Chemo-radiation in Glioblastoma

Summary: This study seeks to investigate if advanced image-analysis of diagnostic scans, can be used to predict how aggressive brain tumors (glioblastoma) respond to standard chemo- and radiation treatment.

Detailed description: Generally, response prediction models seeks to predict time to an event, e.g. time-to-progression and/or overall survival. The aim of this study is to explore the feasibility of establishing an individualized response model, that, based on several morphologic, physiologic and metabolic parameters extracted from computed tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI), is able to predict the tumor response at the level of an imaging voxel, using machine learning techniques.
  Imaging modalities include MRI, PET/CT with 18F-fluroethyltyrosine (18F-FET), and PET/MRI with 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM).

Eligibility: Inclusion Criteria:
  -  Histologically confirmed, primary supratentorial glioblastoma (WHO grade IV).
  Exclusion Criteria:
  -  No informed consent can be obtained
  -  Inability to undergo MRI examination, due to metal implants, pacemaker etc.
  -  Not eligible for Stupp-regimen

Relevance to patient case: not relevant
Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor

Summary: This is an open-label, Phase I, dose escalation study to determine the recommended Phase 2 dose, maximum tolerated dose, and evaluate the safety and pharmacokinetic profile of ABBV-221 in participants with advanced solid tumors likely to exhibit elevated levels of Epidermal Growth Factor Receptor (EGFR).


Eligibility: Inclusion Criteria:
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 2.
  -  Has a solid tumor likely to exhibit elevated levels of EGFR (e.g. head and neck squamous cell carcinoma, non-small cell lung cancer, triple negative breast cancer ,colorectal carcinoma and glioblastoma multiforme).
  -  Has an archived, diagnostic tumor tissue available for analysis.
  -  Has adequate hematologic, renal, cardiac and hepatic function.
  -  Expanded Safety Cohort participants must have confirmed metastatic lung cancer and progressed after receiving prior platinum-containing chemotherapy.
  Exclusion Criteria:
  -  Previously received an EGFR-directed monoclonal antibody within the past 4 weeks.
  -  Has unresolved, clinically significant toxicities from prior anti-cancer therapy defined as > Grade 1 on Common Terminology Criteria for Adverse Events.
  -  History of major immunologic reaction to any IgG containing agent.
  -  Any medical condition which in the opinion of the investigator places the participant at an unacceptably high risk for toxicities.

Relevance to patient case: not relevant
Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: A Study of IDH305 in Patients With Advanced Malignancies That Harbor IDH1R132 Mutations

Summary: A Phase I study of IDH305 in patients with advanced malignancies that harbor IDH1R132 mutations.


Eligibility: Inclusion Criteria:
  -  Documented IDH1R132-mutant tumors
  -  ECOG performance status ≤ 2
  Exclusion Criteria:
  -  Patients who have received prior treatment with a mutant-specific IDH1 inhibitor (with the exception of glioma patients)
  -  Medical conditions that would prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures such as the presence of other clinically significant cardiac, respiratory, gastrointestinal, renal, hepatic or neurological disease.
  -  Acute Promyelocytic Leukemia
  -  Women who are pregnant or lactating
  Other protocol-defined Inclusion/Exclusion may apply

Relevance to patient case: not relevant
Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: The Effect of Duloxetine on Mood, Quality of Life and Cognitive Functioning in Glioblastoma Patients

Summary: Primary tumor glioblastoma is the most common malignant brain. Standard treatment includes biopsy or excision of the tumor in order to obtain a pathological diagnosis, and tumor mass reduction. After the surgery patients are treated with radiation and Temodal. The most common psychiatric symptom in this patient population is depression, valued at up to approximately 50% in patients with glioma . Depression not only adversely affects the quality of life of patients but also impairs the ability and cognitive function due to the complex clinical course of patients with glioblastoma. There is a tendency to give Diagnosis of depression in this patient population, due to a lack of awareness, knowledge and literature on the subject. This study was designed to prospectively randomized, controlled, double-blind study.
  This method of recruitment - patients who undergo resection or biopsy of glioblastoma (newly diagnosed glioblastoma), immediately after diagnosis, patients will receive an explanation about the study and sign a consent form will enter research.

Detailed description: This study was designed to prospectively randomized, controlled, double-blind study.This method of recruitment patients who undergo resection or biopsy of glioblastoma (newly diagnosed glioblastoma), immediately after diagnosis, patients will receive an explanation about the study and sign a consent form will enter research.
  Patients who underwent resection or biopsy of glioblastoma (newly diagnosed glioblastoma), will randomization ratio of 1: 1 by the pharmacist (by age, Karnofsky score, the degree of tumor resection) two research groups:
  Group # 1: consisting of 50 patients who will be treated immediately after diagnosis, 30 mg Cymbalta morning for a week and then a dose exceeding 60 mg for 3 months.
  Group # 2: will include 50 patients treated immediately after diagnosis placebo for 3 months.

Eligibility: Inclusion Criteria:
  -  Patients who signed an informed consent form
  -  Patients who underwent resection or biopsy for GBM
  -  KPS> 70
  Exclusion Criteria:
  -  Patients being treated with antidepressants
  -  Unable to answer the questionnaires because of an inability to communicate
  -  Patients being treated; monoamine oxidase inhibitors (MAOI) CYP1A2 Inhibitors or (CYP2D6 inhibitors (SSRIs such as fluoxetine, paroxetine, or anti-arrhythmia such as quinidine) Patients with Glaucoma, narrow angle
  -  Severe renal dysfunction. According to laboratory criteria specified earlier.
  -  Hepatic insufficiency - which laboratory criteria mentioned earlier.
  -  Pregnant women Patients Dementia
  -  Patients who previously suffered from depression in the past or within 5 years of diagnosis, and currently do not receive drug therapy
  -  Sensitivity to any of its ingredients

Relevance to patient case: not relevant
Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: Magnetic Resonance Spectroscopy (MRS) in Midlife Depression

Summary: The purpose of this study is to determine the impact of inflammation on central nervous system (CNS) glutamate, white matter pathology and alterations in behavior and cognition in middle-aged patients with major depression. Depression is associated with significant alterations in glutamate concentrations and white matter integrity, which has been associated with decreased antidepressant response, poor functional outcome, and cognitive impairment.

Detailed description: This study involves behavioral assessments, neurocognitive testing, blood sampling and magnetic resonance imaging (MRI) scanning. Goals of this study are to determine the impact of inflammation on glutamate concentrations in the basal ganglia and on the integrity of white matter tracts in the basal ganglia and other subcortical regions of middle-aged depressed versus non-depressed individuals and to associated the impact of glutamate and white matter changes on behavioral symptoms among the same group of patients.

Eligibility: Inclusion Criteria:
  -  Willing and able to give written informed consent
  -  A primary diagnosis of depression or bipolar depression-current episode depressed (DSM-5 MDEas diagnosed by the Structured Clinical Interview for DSM-5-Research Version SCID-5-RV44, absence of any Axis I or II pathology)
  -  Score of ≥16 on the Quick Inventory of Depressive Symptomatology (QIDS)-SR43 or (for controls) QIDS ≤5
  Exclusion Criteria:
  -  Unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease
  -  History of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; substance abuse/dependence within 6 months of study entry
  -  Active suicidal ideation
  -  An active eating disorder or obsessive compulsive disorder
  -  Evidence of cognitive impairment
  -  Pregnancy or lactation
  -  Chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), statins, angiotensin receptor blocking agents, antibiotic intake (within 1 week), vaccinations (within 1 week) and intake of omega-3-fatty acid supplements
  -  Use of glucocorticoids or other medications known to suppress the immune system within the past 6 months
  -  Use of antidepressant or other psychotropic drugs known to affect the immune system (e.g. mood stabilizers, antipsychotics, and stimulants) for at least 4 weeks (8 weeks for fluoxetine)

Relevance to patient case: not relevant