araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Does the Aid of MelaFind Affect Clinical Management Decisions

Summary: The objective of this study is to determine and compare the performance of dermatologists (in Germany) on the excision decision against the performance of MelaFind, a non-invasive and objective multi-spectral computer vision system designed as a tool to aid dermatologists in the detection of early melanoma. The hypothesis is that MelaFind's sensitivity is superior to the average excisions sensitivity of dermatologists.
  Another objective is to determine and compare the performance of dermatologists (in Germany) with and without the aid of MelaFind. The hypothesis is that the average excision sensitivity of dermatologists with the aid of MelaFind is superior to the average excision sensitivity of dermatologists without the aid of MelaFind.
  A similar study was previously conducted with dermatologists in the US (NCT01011153). An exploratory objective is to compare the excision decisions of dermatologists from the previous study (in the US) to dermatologists in in this study (in Germany).

Detailed description: Early detection of melanoma is critical for favorable prognosis, since patients with earlier stage melanomas have a much higher probability of survival than with later stages. The traditional method of early detection has been with serial total body skin exams where the health care provider examines all skin surfaces, including mucosa, for suspicious pigmented lesions. The diagnostic performance of dermatologists for melanoma depends on the level of dermatological training. More important than being able to make a diagnosis of melanoma on clinical impression is the ability to make an appropriate decision to excise the lesion. To aid dermatologists in the detection of early melanoma, MelaFind was developed, a non-invasive and objective multi-spectral computer vision system technology. It was designed to generate output - MelaFind Positive or MelaFind Negative- for consideration in the lesion management decisions.
  This survey study will determine and compare the average excision sensitivity to melanoma and specificity of dermatologists (in Germany) without MelaFind output to the average excision sensitivity to melanoma and specificity of dermatologists (in Germany) with MelaFind output. Another purpose is to determine and compare the sensitivity to melanoma and specificity of MelaFind to the average excision sensitivity to melanoma and specificity of dermatologists without MelaFind output.

Eligibility: Inclusion Criteria:
  -Only board certified dermatologists
  Exclusion Criteria:
  -May not have previously participated in MELA Protocols 20061, 20081 or 20063

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Safety Study of a Melanoma Vaccine (GVAX) With or Without Cyclophosphamide in Patients With Surgically Resected Melanoma

Summary: The primary objective of this study is to evaluate the safety and feasibility of administering an allogeneic GM-CSF-secreting lethally irradiated whole melanoma cell vaccine ("melanoma GVAX"), alone or in combination with low dose cyclophosphamide (CPM), for the adjuvant treatment of patients with surgically resected stage IIB-IV melanoma. Secondarily, the investigators will assess in vitro correlates of anti-melanoma immunization by melanoma GVAX, including serological and cellular immune responses in patients treated with either the vaccine alone or the vaccine given with low dose CPM.


Eligibility: Inclusion Criteria:
  -  Any patient age ≥18 years with melanoma of cutaneous or mucosal origin, and with clinicopathologic stage IIB, IIC, III or IV that has been completely resected
  -  Patients must be able to provide informed consent.
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  -  Life expectancy of at least 6 months.
  -  Adequate hematologic function.
  -  Adequate renal function
  -  Adequate hepatic function
  -  Patients of both genders must agree to practice effective birth control during the study period and for at least 4 weeks after the last treatment.
  Exclusion Criteria:
  -  Patients whose primary site of melanoma is ocular.
  -  Are undergoing or have undergone in the past 4 weeks any systemic treatment for melanoma.
  -  Are undergoing or have undergone in the past 2 weeks any surgery or focal radiation therapy.
  -  Have active systemic infections, coagulation disorders (including therapeutic anticoagulation), or other major medical or psychiatric illnesses.
  -  Are known to be positive for hepatitis B surface antigen, anti-Hepatitis C Virus or anti-Human Immunodeficiency Virus (HIV) antibody (because of possible immune effects of these conditions).
  -  Documented history of autoimmune disease, for example, systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis, glomerulonephritis, or vasculitis.
  -  Any form of primary or secondary immunodeficiency. This would include hereditary disorders such as ataxia-telangiectasia or Wiskott-Aldrich syndrome, or acquired immune deficiencies such as following bone marrow transplantation.
  -  Requirement for systemic steroid therapy or immunosuppressive therapy.
  -  Have received any type of cancer immunotherapy, including but not limited to interleukin-2, interferon alfa or melanoma vaccines.
  -  Have been diagnosed with another invasive cancer within the past 3 years.
  -  Radiographic evidence of melanoma recurrence.
  -  Pregnant or lactating women.
  -  Known or suspected hypersensitivity to GM-CSF, pentastarch, hetastarch, corn, Dimethyl sulfoxide, fetal bovine serum or trypsin (porcine origin).

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma

Summary: CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.


Eligibility: Inclusion Criteria:
  For the dose escalation phase:
  1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]). For the dose expansion phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or (ii) confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC) for which no further effective standard therapy exists.
  2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
  3. Evidence of measurable disease
  Exclusion Criteria:
  1. Previous therapy with a MEK inhibitor.
  2. Symptomatic or untreated leptomeningeal disease.
  3. Symptomatic or untreated brain metastasis.Patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastasis must be stable with verification by imaging.
  4. Known acute or chronic pancreatitis.
  5. Clinically significant cardiac disease
  6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818
  7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
  8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
  9. History of thromboembolic or cerebrovascular events within the last 6 months
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Phase 1 Biomarker Study of Anti-PDL-1 in Advanced Melanoma

Summary: The purpose of this study is to evaluate pharmacodynamic changes of BMS-936559 treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with unresectable Stage III or IV Melanoma.


Eligibility: Inclusion Criteria:
  -  Men and women ≥ 18 years
  -  Eastern Cooperative Oncology Group (ECOG) status = 0 to 1
  -  Subjects with unresectable Stage III or IV Melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic Melanoma
  -  Subject must have histologic or cytologic confirmation of advanced Melanoma
  -  Subjects must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  -  Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies
  Exclusion Criteria:
  -  Active or progressing brain metastases
  -  Other concomitant malignancies (with some exceptions per protocol)
  -  Active or history of autoimmune disease
  -  Positive test for human immunodeficiency virus (HIV) 1&2 or known acquired immunodeficiency syndrome (AIDS)
  -  History of any hepatitis
  -  Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti Programmed cell death 1 (PD-1), anti Programmed cell death ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40 or anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibodies

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors

Summary: In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma and patients with other solid tumors will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide.

Detailed description: In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma (n=6) will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma (n=9) and patients with other solid tumors (n=6) will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide. AdCD40L is given by weekly injections of 2.5x10e11 VP, 4x; total dose 1x10e12 VP. A maximum of 30 patients will be included in this trial.
  AdCD40L is an adenoviral nonreplicating vector carrying the human CD40L gene. AdCD40L infects tumor cells upon intratumoral injection and deliver the CD40L gene into the cells whereupon the virus is destroyed. CD40L is then expressed as a membrane-bound protein and interacts with the CD40 receptor expressed by for example dendritic cells (DCs) in the tumor area. DCs mature upon CD40/CD40L interactions and activates tumor-specific T cell responses.

Eligibility: Inclusion Criteria:
  -  Histologically proven diagnosis of malignant solid cancer, ECOG 0-2.
  -  Disease progression on established treatments or patients not eligible to standard options.
  -  Signed informed consent must be obtained.
  Exclusion Criteria:
  -  Pregnancy.
  -  Life expectancy less than 3 months.
  -  Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
  -  Patients with severe systemic autoimmune disease.
  -  Patients that do not consent to that tissue and blood samples are stored in a biobank.

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Non-Interventional Retrospective Correlation Of Tumor Mutational Status To Clinical Benefit Of GIST Patients Treated With Sunitinib

Summary: Retrospective correlation of clinical outcomes data with mutational status in GIST subjects treated with sunitinib.

Detailed description: This is a non-interventional trial. No active patients will participate in this study. Only data generated from the A6181036 study will be utilized for correlational purposes. The A6181036 study data in addition to mutational status data previously analyzed but not collected as part of the A6181036 study in the same patient population

Eligibility: Inclusion Criteria:
  -  GIST subjects that participated in the A6181036 study that had mutational status data analyzed.
  Exclusion Criteria:
  -  Subjects not participating in the A6181036 study

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Brentuximab Vedotin in Patients With CD30-positive Nonlymphomatous Malignancies

Summary: This is an open-label, multicenter, phase 2 clinical trial to evaluate the antitumor activity of brentuximab vedotin as a single agent in patients with CD30-positive nonlymphomatous malignancies.


Eligibility: Inclusion Criteria:
  -  Histologically-confirmed by central review CD30-positive nonlymphomatous malignancy
  -  Have failed, refused, or have been deemed ineligible for standard therapy
  -  Measurable disease
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 or a Karnofsky or Lansky Performance Status score greater than or equal to 70
  Exclusion Criteria:
  -  Primary diagnosis of lymphoma or central nervous system (CNS) malignancy
  -  History of another primary invasive malignancy that has not been definitively treated or in remission for at least 3 years
  -  Evidence of active cerebral/meningeal disease

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Vemurafenib (R05185426) in Poor Performance Status Patients With Unresectable Locally Advanced or Metastatic Melanoma Harboring a V600E/K Mutation

Summary: The purpose of this study is to find out what effects, good and/or bad, vemurafenib has on the patient and the melanoma. Specifically, the investigators want to know how well vemurafenib shrinks melanoma. The investigators also want to find out how well vemurafenib can improve how well the patient functions.


Eligibility: Inclusion Criteria:
  -  Age >18 years old.
  -  Histologic proof of melanoma reviewed and confirmed by MSKCC.
  -  A confirmed EBRAFV600E or KBRAFV600K mutation.
  -  Stage IV melanoma, or advanced stage III not curable by surgery. Patients with active CNS metastases will be allowed on the study.
  -  Measurable disease by RECIST v1.1.
  -  ECOG performance status 3 or 4. The basis for the grading of performance is strict; there must be clear justification of the performance status grade (e.g. patient is confined to bed > 50% of time, or cannot carry out ADLs, or is otherwise disabled by burden of disease such as requiring supplemental O2).
  -  Patients must be able to swallow pills
  -  Adequate hematologic, hepatic and renal function as defined by the following:
  -  Absolute Neutrophil Count ≥ 1.0 x 109/L
  -  Hemoglobin ≥8.0g/dL, occasional transfusions are acceptable as vemurafenib does not have significant hematologic toxicities.
  -  Total bilirubin ≤2.0x the upper limit of normal, ≤3.0x the upper limit of normal if the patient has Gilbert's Syndrome.
  -  Alkaline phosphatase ≤2.0x the upper limit of normal.
  -  AST and ALT ≤2.0x the upper limit of normal.
  -  Serum creatinine ≤ 1.5x the upper limit of normal.
  Exclusion Criteria:
  -  Uveal melanoma as primary.
  -  Concurrent chemotherapy, immunotherapy, or radiotherapy.
  -  Prior treatment with a RAF inhibitor. Other prior chemotherapy, immunotherapy, or radiotherapy will be allowed including prior treatment with a MEK inhibitor Patients must have had complete recovery from any adverse events or toxicities of prior cancer-directed therapies.
  -  Pregnant or lactating women.
  -  A second active malignancy. Prior malignancy will be allowed as long as the patient is known to be free of disease for at least 2 years. Patients with indolent B-cell malignancies will not be eligible.
  -  QTc interval > 500 msec.

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Comparative Microarray Analysis in Primary Cutaneous Malignant Melanoma

Summary: Perturbations in microRNA (miRNA) expression profiles has been reported for cutaneous malignant melanoma (CMM). This study will be an exploratory analysis by miRNA expression profiling using microarrays.

Detailed description: Perturbations in microRNA (miRNA) expression profiles has been reported for cutaneous malignant melanoma (CMM). With regards to a rapidly growing number of newly discovered miRNA sequences, the availability of up-to-date miRNA expression profiles for primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic naevi (BMN) is limited. Patients with PCMM, CMMM and BMN are included in the study to perform an exploratory analysis by miRNA expression profiling using microarrays. Expression levels of miRNA candidates will be validated by TaqMan real-time quantitative polymerase chain reaction (RT-PCR).

Eligibility: Inclusion Criteria:
  -  Primary Cutaneous Malignant Melanoma
  -  Cutaneous Malignant Melanoma Metastases
  -  Benign Melanocytic Naevi
  Exclusion Criteria:
  - Other Skin Cancer than Primary Cutaneous Malignant Melanoma

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: cKIT, BRAF/NRAS Mutations in Advanced Melanoma : Clinical Outcome in Response to Tyrosine-kinase Inhibitors - KitMel Project

Summary: Background: Metastatic melanoma has a devastating prognosis and is one of the top causes of cancer death in young patients. Until now, available therapies were few and unreliable, but recent understanding of melanomas' molecular pathways has improve their classification and new clinical strategies have been proposed.
  Initial studies showed that B-Raf/N-Ras mutations (respectively V600E and Q61) are the most frequent alteration being present in 70 to 80% of melanomas, characterizing non Chronic Sun-induced Damage skins (CSD). These include Superficial Spreading Melanomas (SSM) and Nodular Melanomas (NM). Other studies showed that c-Kit mutations are presently the predominant activating mutation (20 - 40 %) in Acro-Lentiginous Melanomas (ALM), Mucous Melanomas (MM) and in melanomas arising on CSD skin. c-Kit mutation pattern is more complex with four exons being affected leading to different mutations, which incidence and biological impact are less documented.
  BRAF/NRAS genetics alterations drive constantly cell growth, being thus attractive targets. Spectacular results have indeed been obtained with the BRAF inhibitor that targets the V600E BRAF-mutated form. Data from GIST disease revealed that the different c-Kit mutations modulate differently c-Kit function and the response to targeted therapies.
  Because c-Kit targeted therapy is a critical clinical issue, the investigators aimed to identify the most frequent mutations present in our population to propose appropriate screening test and adapt the therapy.
  Methods: 250 melanoma samples corresponding to an homogeneous white-Caucasian population (Brittany, France) will be screened. c-Kit exons 11, 13, 17 and 18 will be sequenced (direct sequencing and pyrosequencing when possible). c-Kit copy number will be quantified by q-PCR and level of c-Kit determined by immunohistochemistry (IHC, CD117). Samples will also be analyzed for B-Raf mutations in codon 464, 466, 469 and 600, and for N-Ras mutations in codon 12, 13 and 61 (Pyrosequencing).
  Expected Results:
  Taken together, the investigators anticipate that the present genetic analysis of the tumours from patients with advanced melanoma will first document the type and frequency of cKit mutations, will confirm or not that BRAF, NRAS and cKit mutations are mutually exclusive and document their repartition in the melanomas sub-types. Finally this study will clue researchers in to how well patients will respond to a therapy that targets the growth-promoting proteins BRAF/NRAS and cKIT.


Eligibility: Inclusion Criteria:
  -  melanoma
  -  white caucasian population

Relevance to patient case: not relevant
Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Sensitivity/Specificity Study of Non-invasive Imaging for Melanoma Diagnosis

Summary: The purpose of this study is to show how well a new device, confocal microscope, works to detect malignant melanoma, a type of skin cancer.


Eligibility: Inclusion Criteria:
  -  Age 12 or older
  -  Patient who has already been selected by their dermatologist for biopsy of a suspicious pigmented lesion and who consents to participate in the study
  -  Signed informed consent
  Exclusion Criteria:
  -  Age < 12 years

Relevance to patient case: not relevant