araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Patients With Refractory, Metastatic Cancer Harboring KIT Mutation or Amplification to Investigate the Clinical Efficacy and Safety of Imatinib Therapy

Summary: KIT is a receptor tyrosine kinase that binds to stem-cell factor (SCF), activating a series of downstream effector pathways. KIT is an established therapeutic target in cancer with activating mutations of KIT, such as gastrointestinal stromal tumors (GIST), and significant benefit is achieved with various small molecule inhibitors of KIT such as imatinib mesylate. Moreover, there is increasing evidence implicating KIT mutations as tractable therapeutic targets in melanoma. Additional information is required to characterize the functional role of low-frequency mutations in KIT and to determine whether amplification of wild type KIT is a real driver that can be targeted therapeutically. Except GIST and melanoma, other solid cancers were reported to have KIT mutation even in low frequency. A molecular profiling of the tumors of patients referred to the phase I clinic at the M.D. Anderson Cancer Center showed KIT mutation in 7 patients in total of 431 patients (2%).
  Hence, the investigators planned this study to apply the molecularly targeted agent, imatinib to various types of cancers harboring KIT mutation or amplification.


Eligibility: Inclusion Criteria:
  1. age ≥ 20
  2. advanced, refractory cancer patients who failed standard of care (SOC)
  3. KIT aberration: defined as mutation in exons 9, 11, 13, 17 or 18, or nanostring CNV by quantitative PCR (greater than 3 copies) or subject with specific sensitivity (Z-score<-1) to imatinib by Avatar scan whose disease has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy
  4. ECOG performance status of 0~2
  5. measurable or evaluable lesion per RECIST 1.1 criteria
  6. adequate marrow, hepatic, renal and cardiac functions
  -  Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
  -  Total serum bilirubin ≤ 1.5 x ULN
  -  Absolute neutrophil count(ANC) ≥ 1,500/uL
  -  Platelets ≥ 100,0000/uL
  -  Hemoglobin ≥ 9.0 g/dL
  7. provision of a signed written informed consent
  Exclusion Criteria:
  1. severe co-morbid illness and/or active infections
  2. pregnant or lactating women
  3. history of major surgery or radiotherapy within 4 weeks
  4. active CNS metastases not controllable with radiotherapy or corticosteroids (however, CNS metastases (except for leptomeningeal seeding) are allowed if controlled by gamma knife surgery or surgery or radiotherapy or steroid)
  5. known history of hypersensitivity to study drugs

Relevance to patient case: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: RM-493 Treatment Trial in Proopiomelanocortin (POMC) Deficient Patients

Summary: The purpose of this study is to evaluate the effects of a once daily subcutaneous (SC) injection of RM-493, in subjects with POMC (propiomelanocortin) or other related rare genetic mutations, on body weight, metabolic function and blood pressure. Patients who respond during the initial 84 days of treatment can enter into long-term (2-year) extensions. The study drug (RM-493) will be administered in an unblinded fashion.


Eligibility: Inclusion Criteria:
  -  Written informed consent
  -  Homozygous or compound heterozygous (different gene mutation on both alleles) POMC, LEPR or PCSK1 gene mutation
  -  Obesity (BMI > 30 kg/m2; + 2 BMI SDS)
  -  No other therapeutic option, which might cure the patient (e.g. bariatric surgery (see chapter 8))
  -  Negative Pregnancy test
  -  Highly effective contraception in women (defined as pearl index < 1), if necessary also for partners of test persons)
  -  No participation in other clinical trials according to AMG (Arzneimittelgesetz) (2 months before and after) at the time of this trial
  -  Normal or minimally elevated blood pressure (measured in 24RR monitoring or similar methods) according the guidelines of the ESH (European Society of Hypertension) and Deutsche Hochdruckliga: systolic > 159 mmHg/diastolic 99 mmHg
  -  sufficient kidney and liver function (Creatinine, ALT, AST)
  -  normal values Alanine-Aminotransferase (ALT) (female): < 31 U/l
  -  normal values Alanine-Aminotransferase (ALT) (male): < 41 U/l
  -  normal values Aspartate-Aminotransferase (AST) (female > 17 years): < 35 U/l; (female < 17 years): 16- 46 U/l
  -  normal values Aspartate-Aminotransferase (AST) (male > 17 years): < 50 U/l; (male < 17 years): 16-46 U/l
  -  normal values bilirubins (male and female) up to 1,2 mg/dl
  -  normal values Creatinine (female > 15 years): 0,51-0,95 mg/dl) ; (female < 15 years): 0,46-0,77 mg/dl
  -  normal values Creatinine (male > 15 years): 0,67 - 1,17 mg/dl) ; (male < 15 years): 0,46-0,77 mg/dl
  Exclusion Criteria:
  -  Pregnancy or Breastfeeding
  -  All contraindications against study medication (including auxiliary substances)
  -  Interactions with study medication
  -  Participation of the patient in a clinical study within the last 2 months
  -  Intolerance against albumin
  -  Concomitant diseases, impaired organ functions, except for known, concurrent GI disorders or other clinical findings expected in PCSK1 or LEPR gene disorders
  -  Renal insufficiency (Creatinine > 0,95 mg/dl (female), > 1,17 mg/dl (male))
  -  Impaired liver function (Bilirubins > 1.2 mg/dl)
  -  Neurological / psychiatric diseases
  -  HIV Infection
  -  Active Hepatitis B or C
  -  Melanoma or Melanoma occurrence in the family history
  -  Non-compliance
  -  Subjects who are legally detained in an official institution

Relevance to patient case: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: A Study of Idasanutlin With Cytarabine Versus Cytarabine Plus Placebo in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Summary: This study is designed to compare Overall Survival (OS) in participants with relapsed or refractory Acute Myeloid Leukemia (AML) treated with idasanutlin in combination with cytarabine versus participants treated with placebo and cytarabine. Participants will receive induction treatment with idasanutlin/placebo and cytarabine (Cycle 1). Responding patients may continue to receive a maximum of further two cycles of consolidation (Cycle 2 and Cycle 3). Complete remission (CR), CR with incomplete platelet count recovery (CRp), overall remission rate (ORR), event-free survival (EFS), leukemia-free survival (LFS) and percentage of participants with an allogeneic hematopoietic stem cell transplant (HSCT) will also be compared between treatment arms. This study will include participants without (TP53 wild-type) and with TP53 mutations.


Eligibility: Inclusion Criteria:
  -  Age >=18 years
  -  Documented/confirmed 1st/2nd refractory/relapsed acute myeloid leukemia (AML) using World Health Organization classification, except acute promyelocytic leukemia.
  -  No more than 2 prior induction regimens (excluding prior hematopoietic stem cell transplant [HSCT]) and one must have included cytarabine with an anthracycline (or anthracenedione)
  -  Eastern Cooperative Oncology Group performance status of 0 to 1
  -  Patient should be a potential candidate for allogeneic HSCT
  -  Adequate hepatic and renal function
  Exclusion Criteria:
  -  Patients with first complete remission (CR1) duration of >1 year AND age <60 years
  -  Patients with AML with myelodysplasia related changes, or AML that has developed as a consequence of an antecedent hematological disorder (AHD)
  -  AML secondary to any prior chemotherapy unrelated to leukemia
  -  Patients who have received more than two prior cytarabine containing induction regimens for AML
  -  Patients who have relapsed within 90 days after therapy with intermediate-dose cytosine arabinoside (IDAC) or high-dose cytosine arabinoside (HiDAC) containing regimens
  -  Patients who have received allogeneic HSCT within 90 days prior to randomization.
  -  Patients who have received immunosuppressive therapy for graft versus host disease (G versus HD) within 2 weeks prior to study start
  -  Prior treatment with a Murine Double Minute 2 (MDM2) antagonist
  -  Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy
  -  Patients with a history of other malignancy within 5 years prior to screening.
  -  Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  -  Pregnant or breastfeeding patients

Relevance to patient case: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Circulating Tumor DNA and Follow-up of BRCA1 Mutation Carriers (CirCa 01)

Summary: BRCA1 carriers who are at high risk of developing either a relapse and/or a new cancer growth will be included. These patients will be followed up during 30 months (2,5 years) with mutated TP53 mutation detection or during 42 months (3,5 years) with mutated TP53 mutation detection and circulating tumor cells detection (CTC) performed at each hospital visit (for technical reason only patients included at Institut Curie will be proposed to participate to the CTC substudy).


Eligibility: Inclusion Criteria:
  1. Patient with no evidence of any invasive tumor mass at inclusion (clinical and, if any, radiological exams)
  2. Carriers of known germline BRCA1 deleterious mutation (a personal history of cancer is NOT mandatory).
  3. Age ≥ 30 years for patient with personal previous history of cancer
  4. Age ≥ 40 years for patient without personal previous history of cancer
  5. Patient who a follow-up visit is scheduled in the including center at least once a year
  6. Patient having health care insurance
  7. Signed informed consent by patient
  Exclusion Criteria:
  1. Patient presenting with invasive tumor masses (e.g. stage IV cancer or localized cancer not yet surgically removed)
  2. Carriers of germline BRCA1 variant of unknown significance
  3. Carriers of germline BRCA2 deleterious mutation or variant
  4. Individuals with a low risk of BRCA1-related tumor growth, i.e. women who underwent prophylactic bilateral mastectomy AND adnexectomy.
  5. Any medical or other condition that in the Investigator's opinion rendered the patient unsuitable for this study
  6. Patient deprived from ability to decide on her own.
  7. Patient unable to have a regular follow up for geographical, social or psychological reasons.

Relevance to patient case: possibly relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: fPAM for the in Vivo Depth Measurement of Pigmented Lesions and Melanoma Depth

Summary: The investigators propose the use of functional photoacoustic microscopy (fPAM) to evaluate both benign and malignant pigmented lesions for tumor depth. Through fPAM analysis followed by histological examination, the investigators anticipate that they will be able to non-invasively determine tumor depth of pigmented lesions (moles and melanoma). In melanoma, tumor depth (Breslow's depth) is not only an important prognostic indicator, but also directs surgical treatment. The ultimate goal is to develop a sensitive clinical tool that will allow non-surgical evaluation of pigmented lesions, which eventually, will aid in melanoma diagnosis and management - potentially an earlier and more definitive surgical management.
  In addition, the investigators propose to use the combination of fPAM and single-cell PAM to respectively image CTCs in trunk vessels and cuticle capillaries. Based on the investigators' murine models, the investigators anticipate that they will be able to differentiate CTCs from other blood cells and reliably calculate CTC concentration in a non-invasive manner. CTC concentration has been demonstrated to be a valuable indicator of a melanoma's metastatic potential and a potential tool in evaluating treatment efficacy. The ultimate goal is to develop a sensitive imaging device that will allow accurate evaluation of the risk of melanoma recurrence and metastases, that may facilitate treatment monitoring.


Eligibility: Inclusion Criteria:
  Outcome Measure #1 and #2
  -  Healthy individuals with pigmented lesions or a partially biopsied melanoma whose treatment plan includes excision
  -  Participants must be 18 years or older
  -  Participants must be able to understand and willing to sign a written informed consent document
  Outcome Measures #3 and #4
  -  Patients with either cutaneous, visceral or brain melanoma metastases.
  -  Participants must be 18 years or older.
  -  Participants must be Eastern Cooperative Oncology Group (ECOG) status 0-3.
  -  Participants must be able to understand and willing to sign a written informed consent document.
  Exclusion Criteria:
  -  Minors, pregnant patients, incarcerated individuals, and individuals unable to give informed consent will be excluded from this study
  -  ECOG status > 3

Relevance to patient case: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Biomarkers for the Activity of Immune Checkpoint Inhibitor Therapy in Patients With Advanced Melanoma

Summary: 1. Screen and recruitment: patients will be screened based on their prior history and intention to initiate treatment with an immune checkpoint inhibitor.
  2. Study phase:
  -  Collection of baseline demographic data, prior disease history, nature of ICI therapy, outcome data of ICI therapy (treatment disposition, toxicity, tumor response and survival).
  -  Collection of blood samples will be performed every 3 to 4 weeks for the first year on ICI therapy and every 6 to 12 weeks thereafter until the end of ICI therapy, disease progression, death or loss to follow-up. Collection of blood samples will be aligned with the visits necessary for the administration of the ICI therapy.
  -  Collection of archival melanoma metastasis tissues will be performed on a continuous basis and be triggered by availability of such tissue following therapeutic resections of melanoma metastases.
  3. Follow-up phase

Detailed description: 1. Screen and recruitment: patients will be screened based on their prior history and intention to initiate treatment with an immune checkpoint inhibitor. This screening of candidate patients by the investigators will be non-interventional. Patients that are considered eligible candidates will be invited to participate in this study and to Page 3/18 provide written informed consent.
  2. Study phase:
  -  Collection of baseline demographic data, prior disease history, nature of ICI therapy, outcome data of ICI therapy (treatment disposition, toxicity, tumor response and survival).
  -  Collection of blood samples will be performed every 3 to 4 weeks for the first year on ICI therapy and every 6 to 12 weeks thereafter until the end of ICI therapy, disease progression, death or loss to follow-up. Collection of blood samples will be aligned with the visits necessary for the administration of the ICI therapy.
  -  Collection of archival melanoma metastasis tissues will be performed on a continuous basis and be triggered by availability of such tissue following therapeutic resections of melanoma metastases.
  3. Follow-up phase: patients who stop treatment with the immune checkpoint inhibitor will be followed-up for

Eligibility: Inclusion Criteria:
  1. Histologically confirmed malignant melanoma;
  2. AJCC Stage IIIC or IV melanoma with evaluable disease;
  3. Treatment with an immune checkpoint inhibitor;
  4. Willing and able to give written informed consent;
  5. Accessible for treatment and follow-up;
  Exclusion Criteria:
  -  non

Relevance to patient case: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Comparison Between Hemitrapeziectomy and Total Trapeziectomy With Ligament Reconstruction and Tendon Interposition in Trapeziometacarpal Osteoarthritis II-III Eaton-Littler

Summary: 1. Introduction:
  Investigators think that surgery with preservation of healthy joints (hemitrapeziectomy) in trapeziometacarpal osteoarthritis without affecting sapho-trapezo-trapezoid joints, is better for scaphoid stability by preventing its collapse and thus preserving the stability of the carpus.
  2. Objectives and Hypothesis:
  Ligamentoplasty with partial trapeziectomy in grades II-III Eaton presents better results in the pollicis-lateral pinch (key pinch) strength than ligamentoplasty with total trapeziectomy.
  Main Objective:
  To demonstrate using the dynamometer that the postoperative key pinch strength higher using ligamentoplasty with partial trapeziectomy in grades II-III Eaton.
  Secondary objectives:
  To measure the collapse of the first column of thumb using calibrated radiographic analysis. Pain (E.V.A Scale). Range of motion (measured with goniometer). Quality of life (DISABILITIES OF THE ARM, SHOULDER AND HAND questionnaire).
  3. Methodology:
  It is a single-center randomized trial, parallel-group, in which two types of surgical techniques (TT - TP) will be compared. Patients will be randomized in this two techniques will be followed for one year, in routine clinical practice.


Eligibility: Inclusion Criteria:
  -  Patients with Osteoarthritis in the trapeziometacarpal joint determined by the classification of Eaton-Littler (stages II-III) with trapeziometacarpal joint pain, loss of function, that were included in surgical waiting list and have accepted under informed consent, including the study.
  Exclusion Criteria:
  -  Patients with osteoarthritis Eaton-Littler (stage IV).
  -  Patients with huge affection of trapezium subchondral cysts and poor quality of trabecular bone.
  -  Cognitive impairment.
  -  Old fracture with impairment of the same extremity.
  -  Rheumatic active illness.
  -  Patients who withdraw their informed consent, or in case of impossibility of opinion by clinical status, whose legal guardians or close relatives to withdraw their informed consent to participate in the study.
  -  Patients who for any reason not related to the indication needed discontinue study participation or impossible to carry out assessments under more than two follow-up visits.
  -  Patients in whom it is considered that participation in the clinical study can be a prejudice, the physician responsible for patient care opinion.

Relevance to patient case: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Optimized Caloric-proteic Nutrition in Septic and Septic Shock Patients

Summary: In this pilot randomized prospective controlled trial the investigators intend to compare the use of a nutritional therapy based on caloric intake determined by indirect calorimetry and high protein intake with nutritional regimen based on 25 Kcal / kg / day and protein intake usually recommended for critically ill patients (1.4 to 1.5 grams / kg / day of protein).


Eligibility: Inclusion Criteria:
  -  Patients admitted to the ICU with sepsis and septic shock according to 3rd International Sepsis Consensus Conference Definitions for sepsis and septic shock
  -  Mechanically ventilated
  -  Expected length of stay in ICU ≥ 4 days
  -  Written informed consent obtained from authorized surrogates
  Exclusion Criteria:
  -  Pregnancy
  -  Requirement for inspired oxygen content (FIO2) > 0.60
  -  High output bronchopleural fistula

Relevance to patient case: not relevant
Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: A Study to Evaluate the Efficacy of Venetoclax in Relapsed/Refractory Participants With Chronic Lymphocytic Leukemia (CLL) Including Those With 17p Deletion or TP53 Mutation or Those Who Have Received a Prior B-cell Receptor Inhibitor.

Summary: The purpose of this open-label, single-arm study is to evaluate the efficacy of venetoclax monotherapy in approximately 250 participants with relapsed/refractory CLL including those with the 17p deletion or TP53 mutation (assessed by local lab) OR those who have received prior treatment with a B-cell receptor inhibitor. The starting dose of venetoclax is 20 mg once daily. The dose must be gradually increased over a period of 5 weeks up to the daily dose of 400 mg. Participants may continue receiving venetoclax for up to 2 years. After the treatment period, participants may continue on into a 2-year follow-up period.


Eligibility: Inclusion Criteria:
  -  Participant has Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2
  -  Participant has relapsed/refractory disease (received at least 1 prior therapy)
  -  Participant has diagnosis of CLL that meets published 2008 Modified IWCLL NCI-WG Guidelines and:
  -  has an indication for treatment according to the 2008 Modified IWCLL NCI-WG criteria
  -  has clinically measurable disease (lymphocytosis greater than 5 × 109/L and/or palpable and measurable nodes by physical exam and/or organomegaly assessed by physical exam)
  -  In addition, participants:
  -  may harbor 17p deletion or TP53 mutation, assessed by a local laboratory in bone marrow or peripheral blood AND/OR
  -  may have been previously treated with a prior B-cell receptor inhibitor
  -  Participant must have adequate bone marrow function, coagulation profile, renal, and hepatic function, per laboratory reference range at Screening
  Exclusion Criteria:
  -  Participant has developed Richter's transformation or Prolymphocytic leukemia
  -  Participant has previously received venetoclax
  -  History of active malignancies other than CLL within the past 2 years prior to first dose of venetoclax, with the exception of:
  -  adequately treated in situ carcinoma of the cervix uteri
  -  adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
  -  previous malignancy confined and surgically resected (or treated with other modalities) with curative intent
  -  Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to Screening), including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura despite low dose corticosteroids
  -  Participant has undergone an allogeneic stem cell transplant grade 2:
  -  Any anti-cancer therapy including chemotherapy, or radiotherapy;
  -  Investigational therapy, including targeted small molecule agents
  -  Participant is human immunodeficiency virus (HIV) positive
  -  Participant has known allergy to both xanthine oxidase inhibitors and rasburicase

Relevance to patient case: not relevant