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

Clinical trial: Comparison of AZD6244 in Combination With Dacarbazine Versus (vs) Dacarbazine Alone in BRAF Mutation Positive Melanoma Patients

Summary: To assess the efficacy in terms of overall survival of AZD6244 in combination with dacarbazine, compared with dacarbazine alone, in first line patients with BRAF mutation positive advanced cutaneous or unknown primary melanoma


Eligibility: Inclusion Criteria:
  -  Histological or cytological confirmation of advanced (inoperable stage III and stage IV) cutaneous or unknown primary melanoma
  -  Tumor sample confirmed as BRAF mutation positive
  Exclusion Criteria:
  -  Diagnosis of uveal or mucosal melanoma
  -  Any prior Investigational therapy comprising inhibitors of Ras, Raf or MEK
  -  Having received an investigational drug within 30 days of starting treatment, or have not recovered from side effects of an investigational drug

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

Clinical trial: Whole Body 111In-exendin-4 Imaging Study in Insulinoma Patients

Summary: The purpose of this study is to determine whether the investigators' new imaging modality (111In-exendin-4) has advantages in detecting insulinomas in comparison to conventional imaging.

Detailed description: Insulinomas arise from pancreatic cells and are the most frequent hormone-active tumours of the pancreas. Insulinomas produce insulin and can become life threatening if they cannot be localised and removed surgically. Complete tumour resection cures most patients, hence surgery is the treatment of choice for begin and malignant insulinomas. The potential for surgical cure necessitates accurate tumour localisation before surgery because preoperative imaging facilitates the detection of small localised, multiple and metastatic insulinomas. However, the successful localisation of insulinomas is an challenging problem since approximately 30% of insulinomas cannot be visualised radiographically.
  A novel nuclear medicine scanning method using radioactive exendin-4 (111In-exendin-4) has recently been developed for imaging of insulinomas. 111In-exendin-4 accumulates specifically in insulinoma cells via the glucagon-like peptide-1 (GLP-1) receptor. The accumulation of 111In-exendin-4 can be visualised by the use of a special camera (Single Photon Emission Computed Tomography (SPECT) camera) that detects radioactivity and lights up tumours as hot spots.
  The decision to perform surgery is independent of this study. If surgery is performed a small sample of the tumor will be used for identifying the sites where 111In-exendin-4 binds to the tumor.

Eligibility: Inclusion Criteria:
  -  Biochemically proven endogenous hyperinsulinism confirmed by hypoglycaemia with neuroglycopenic symptoms, inadequately high serum insulin and C-peptide concentrations and negative sulfonylurea screening as well as low serum beta-hydroxybutyrate concentrations
  -  Able and willing to provide written informed consent
  Exclusion Criteria:
  -  Renal insufficiency (creatinine > 140 micromol/l)
  -  Pregnancy or positive pregnancy test which will be performed in all patients without contraception and aged < 50 years
  -  Allergy to exendin-4 (Byetta®)

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

Clinical trial: Study of Tumor Tissue Samples From Patients With Stage I, Stage II, or Stage III Malignant Melanoma

Summary: RATIONALE: Studying the genes expressed in samples of tumor tissue from patients with cancer may help doctors identify biomarkers related to cancer.
  PURPOSE: This research study is looking at tumor tissue samples from patients with stage I, stage II, or stage III malignant melanoma.

Detailed description: OBJECTIVES:
  -  Determine the genetic profile of primary melanomas with and without synchronous regional nodal involvement by examining for 1) activating mutations B-Raf and N-Ras associated with melanoma development, and 2) allelic imbalances across the genome.
  -  Compare the genetic profile of primary melanomas from patients with and without lymph node involvement.
  -  Determine the combinations of genetic lesions that correlate with nodal metastasis by adopting a statistical machine learning approach to build a lesion-based classifier for nodal metastasis.
  OUTLINE: Laser capture microdissection is performed on the archived tissue samples to isolate melanoma cells. DNA is then purified from the samples and amplified using PCR. Matrix-assisted laser desorption/ionization (MALDI)-time of flight mass spectrometry technology is used to detect mutations of B-Raf and N-Ras. Single nucleotide polymorphism arrays are also performed.
  Information about the patient's demographics (e.g., TNM staging, sex, age, and tissue collection dates) will be gathered by chart review or from the Multidisciplinary Melanoma Conference at University Hospitals tumor conference report in order to match cases.

Eligibility: Inclusion Criteria:
  -  Node positive Group (experimental group)
  -  Primary melanoma > 2 mm in depth
  -  Metastasis must be > 0.1 mm and detectable by IHC or hematoxylin and eosin (H&E) to be considered node positive
  -  Slides and block for primary and node must be archived in UH dermatopathology
  -  Node Negative Group (control group)
  -  Primary melanoma > 2 mm in depth
  -  A negative sentinel lymph node must be negative by IHC and H&E
  -  No stage IV disease
  -  No acral and mucosal histology
  -  No history of prior invasive melanoma
  -  Underwent primary excision and sentinel lymph node biopsy within 3 months of each other
  -  Archived tissue available
  -  Slides and block for primary tumor and node biopsy must be archived in University Hospitals Case Medical Center (UH) dermatopathology
  Exclusion Criteria:
  -  Acral and mucosal histology
  -  Previous diagnosis of invasive melanoma
  -  previous chemotherapy or immunotherapy
  -  patients who are found to have stage IV disease during workup

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

Clinical trial: Ultraviolet Light Exposure and Immunosuppression in Cutaneous Melanoma

Summary: This project seeks to understand differences in the serum vitamin D levels and immune status in cutaneous malignant melanoma patients with different UV exposure histories in New Mexico.

Detailed description: It is well established that ultraviolet radiation (UV) exposure is related to the development of melanoma. There is also evidence that immune reactions are altered after UV exposure in the skin (locally) and perhaps throughout the body (systemically). Additionally, while the role of vitamin D and melanoma development has not been fully established, UV-B exposure is essential for vitamin D production in the skin. Increased sun exposure is also related to the presence of solar elastosis, which might protect (1) or improve survival from melanoma. Thus, melanoma represents a unique model for studying UV exposure, the immune system, and vitamin D. Malignant melanoma is an antigenic cancer; therefore, the role of UV exposure-induced immunosuppression and vitamin D production in the recognition, destruction and growth inhibition of cancerous melanocytes is worth further study.
  To underscore the importance of this project, the Scientific Advisory Committee of the Melanoma Research Foundation and the Steering Committee of the Society of Melanoma Research have indicated a need to collect more human data on the host immune response mechanisms in melanoma and also to focus on the skin as a whole microenvironment, moving away from only in vitro experiments.

Eligibility: Inclusion Criteria:
  -  Resident of New Mexico
  -  Age between the 1 and 95
  -  Newly diagnosed with cutaneous invasive melanoma; any stage permitted (ICDO C44.0-9) between September 1, 2008 and December 31, 2011.
  -  SSM (superficial spreading melanoma) and NM (nodular melanoma) histological subtypes are allowed
  -  Access to a telephone or be able to participate in a personal interview at the clinic
  -  Physically and mentally competent to complete a 1-hour telephone or personal interview
  Exclusion Criteria:
  -  Ocular melanoma, LMM (lentigo maligna melanoma) or ALM (acral lentigo melanoma), and mucosal melanoma cases.
  -  No access to a telephone or is not able to meet with the interviewer.

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

Clinical trial: A Study of AMNN107 in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation

Summary: The purpose of this study is to determine whether nilotinib is efficacious in the treatment of metastatic and/or inoperable melanoma harboring a c-Kit mutation.

Detailed description: This trial began as a multi-center, randomized, Phase III, controlled trial for nilotinib vs (DTIC) dacarbazine to assess the efficacy and safety of nilotinib (400 mg bid) in patients with c-Kit mutated metastatic and/or inoperable melanoma. The study was open to patients with mucosal or acral melanoma.
  Due to substantial difficulties identifying and recruiting eligible patients, the trial design was altered from a randomized, two-arm, Phase III study to a single-arm, Simon two-stage Phase II study with protocol Amendment 2 (27-Jul-2011). While the original protocol required the recruitment of 120 patients, this amendment required the study to recruit only 41 patients (patients randomized to nilotinib prior to Amendment 2 were to be counted in this total, but those randomized to dacarbazine ( DTIC ) DTIC were not). Patients randomized to DTIC were allowed to cross-over to nilotinib, either immediately or at the time of progression.

Eligibility: Inclusion Criteria:
  1. Histologically confirmed mucosal or acral 2. Presence of a c-Kit mutation of exon 9, 11 or 13, or mutations Y822D and mutations D820Y, Y823D of exon 17, as confirmed by the central laboratory 3. Stage III unresectable or stage IV disease 4. The presence of one or more measurable lesions as detected by radiological or photographic methods and assessed according to RECIST 1.0. Lesions must have a size of at least 10mm at longest diameter (using a slice thickness of 5 mm)or double the slice thickness to be considered a target lesion. Target lesions should not be selected in previously irradiated fields unless there is clear evidence of progression 5. WHO performance status 0 - 2
  Exclusion Criteria:
  1. C-Kit mutation of exons 17(except mutations D820Y, Y822D or Y823D) or any other exon not allowed by the inclusion criteria
  2. Patients with c-Kit amplifications only and no mutation
  3. Patients with any history of brain metastases
  4. Patients who have had any prior treatment with TKIs
  5. Patients receiving medications or herbal extracts which interfere with nilotinib metabolism which are not discontinued by the time of the baseline visit
  6. Acute or chronic liver or renal disease considered unrelated to melanoma
  Other protocol-defined inclusion/exclusion criteria may have applied.

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

Clinical trial: Study of BMS-650032 With Peginterferon Alfa-2a Plus Ribavirin

Summary: The purpose of this study is to identify one or more doses of BMS-650032 that, when used in combination with pegylated-interferon alpha and ribavirin are safe and demonstrate sufficient activity against hepatitis C virus (Genotypes 1 and 4).


Eligibility: Inclusion Criteria:
  -  Subjects chronically infected with HCV genotype 1 (Phase 2a and Phase 2b)
  -  Subjects chronically infected with HCV genotype 4 (Phase 2b only)
  -  HCV RNA viral load of ≥ 10*5* IU/mL at screening
  -  BMI of 18 - 35 kg/m² at screening
  Exclusion Criteria:
  -  Cirrhosis (Phase 2a only)
  -  Decompensated cirrhosis (Phase 2b)
  -  Co-infection with HBV or HIV
  -  Hepatocellular carcinoma
  -  Prior treatment with anti-HCV drugs

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

Clinical trial: An Immunonutritional Approach to the Prevention of Skin Cancer

Summary: Skin cancer incidence continues to rise and ultraviolet radiation (UVR) in sunlight is the principal cause. Solar UVR can promote cancer development through its ability to suppress the immune system. The purpose of this study is to determine whether dietary supplementation with omega-3 polyunsaturated fatty acids can protect human skin from UVR-induced immunosuppression.

Detailed description: Skin cancer is one of the most common human cancers with a rising incidence and considerable negative impact on human health. Exposure to ultraviolet radiation (UVR) in sunlight is the major aetiological factor in skin cancer initiation and progression. Human case-control studies have reported an inverse relationship between dietary fish or omega-3 polyunsaturated fatty acid (PUFA) intake and occurrence of non-melanoma skin cancer. Omega-3 PUFA have the potential to reduce the risk of photocarcinogenesis primarily by their ability to reduce production of prostaglandin E2 and consequently photoimmunosuppression. To date, no studies have assessed the impact of omega-3 PUFA on skin photoimmunosuppression in humans.
  OBJECTIVE: To examine the potential of dietary omega-3 PUFA to protect against UVR-induced cutaneous immunosuppression in humans.
  STUDY DESIGN: A double-blind randomised controlled nutritional study in 64 healthy human volunteers with nickel sensitivity. Volunteers will receive 3 months dietary supplementation with either omega-3 PUFA (n=32) or gelatine (n=32) both provided in identical gelatine capsules.
  The aim is to quantify the influence of omega-3 PUFA on:
  1. UVR-induced suppression of clinical contact hypersensitivity (CHS) responses
  2. UVR-induced modulation of epidermal Langerhans cell trafficking
  3. UVR-induced modulation of levels of immunoregulatory mediators

Eligibility: Inclusion Criteria:
  -  Pre-menopausal females
  -  Sun-reactive skin type I / II
  -  Reporting allergy to jewellery with nickel content
  Exclusion Criteria:
  -  History of atopy
  -  History of skin cancer
  -  History of a photosensitivity disorder
  -  Sunbathing (including sunbeds) in the last 3 months
  -  Pregnancy
  -  History of cardiac disease
  -  Taking photoactive medicine
  -  Not able to eat fish or gelatine
  -  Taking fish oil supplements prior to the study

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

Clinical trial: Investigator-Sponsored Protocol - Continued Use of Ibalizumab

Summary: This protocol serves to extend the successful treatment for HIV positive patients beyond the endpoints provided by the Phase 2b TaiMed Biologics-sponsored protocol TMB202 (entitled "A Phase 2b Randomized, Double-Blinded, 48-Week, Multicenter, Dose-Response Study of Ibalizumab Plus an Optimized Background Regimen in Treatment-Experienced Patients Infected with HIV-1 (Amended to 24 Week Study)"), for 24 weeks. Ibalizumab may be administered beyond 24 weeks under this protocol as supply permits and patients continue to demonstrate virologic response.

Detailed description: Ibalizumab is to be administered to HIV-infected patients that have responded (defined as a minimum 0.7 log10 decline in HIV-1 viral load from TMB-202 Baseline) on the TMB-202 protocol. In addition to the investigator-selected Optimized Background Regimen, patient(s) will continue to receive the TMB-202 randomized dose of ibalizumab in open-labeled fashion (800mg IV every two weeks or 2000mg IV every four weeks) as per their original drug assignment for the TMB-202 protocol.

Eligibility: Inclusion Criteria:
  -  Capable of understanding and have voluntarily signed the ICF
  -  Have documented HIV-1 infection
  -  Have successfully completed Protocol TMB202 (Amendment 2)(Week 16)
  -  Have had at least a 0.7 log10 decline in HIV-1 RNA from baseline at Week 16 and beyond while in TMB202 and are no longer eligible to participate in TMB-202 due to TMB-202 protocol-defined virologic failure
  -  Have not withdrawn or been discontinued from TMB202 9Amendment 2) for any reason
  -  Are able and willing to comply with all protocol requirements and procedures
  -  Are 18 years of age or older
  -  If sexually active, are willing to use an effective method of contraception during the study and for 30days after the last administration of the study drug.
  Exclusion Criteria:
  -  Any active AIDS-defining illness per Category C except for cutaneous Kaposi's sarcoma and wasting due to HIV
  -  Any significant disease (other than HIV-1 infection) or clinically significant findings, including psychiatric and behavioral problems, medical history and/or physical examination that, in the investigator's opinion, would preclude the patient from participating in this study
  -  Any current alcohol or illicit drug use that, in the investigator's opinion, will interfere with the patient's ability to comply with the study schedule and protocol evaluations
  -  Any previous clinically significant allergy or hypersensitivity to any excipient in the ibalizumab formulation

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

Clinical trial: Prophylactic Irradiation of the Para-Aortic Lymph Nodes and Supraclavicular Lymph Nodes in Locally Advanced Uterine Cervical Cancer

Summary: This study is an open-label, randomized study, which is designed to investigate the efficacy of Extended-field irradiation (EFI) on reducing recurrences at the para-aortic lymph node (PAN) and supraclavicular lymph nodes, and also on improving disease-free survival of locally advanced uterine cervical cancer. This study includes a translational research component in that all the primary tumors and lymph node are stained with Sema4c, before randomization. According to the investigators study result, patients with more pelvic lymph node metastasis are more likely to develop distant metastasis including the recurrences at PAN and supraclavicular lymph node. Primary cervical cancer tissues and lymph nodes are examined for expression of Sema4c just after registration, and before the patients are randomized to each arm (pelvis only vs. EFI). The investigators expect a higher benefit of EFI in patients with Sema4c-positive lymph node.


Eligibility: Inclusion Criteria:
  -  Patients (who have been adequately clinically staged) with primary, untreated, histologically confirmed invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, FIGO stage IB1 with pelvic lymph node metastasis, IB2, IIA(≥4cm in tumor size, or pelvic LN metastasis), IIB, IIIA, IIIB? with only unilateral pelvic wall extension
  -  Patients with negative, para-aortic lymphadenopathy determined by pelvic MRI and/or PET/CT scan.
  -  Patients with adequate bone marrow function: ANC greater than or equal to 1,500/ul, platelets greater than or equal to 100,000/ul at the beginning.
  -  Patients with adequate renal function: creatinine equal to or less than 2.0 mg/dL.
  -  Patients who have signed an approved informed consent and authorization
  -  Patients with ECOG Performance Status of 0, 1, 2 and Karnofsky Performance Scale of 100, 90, 80, 70, 60, 50
  -  Age: 18≤age≤80
  Exclusion Criteria:
  -  Stage IIIb with bilateral pelvic wall extension and stage IVB lesions are not eligible.
  -  Patients with histology other than squamous, adeno, adenosquamous cell carcinoma
  -  Patients who have received prior radiotherapy of pelvis or total hysterectomy Patients who have diagnosis of other malignant tumors other than non-malignant melanoma skin cancer or stage I. II papillary, follicular thyroid cancer.

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

Clinical trial: A Study of Avastin (Bevacizumab) in Combination With Fotemustine in Patients With Metastatic Melanoma

Summary: This study will investigate the efficacy and safety of bevacizumab + fotemustine in patients with stage IV melanoma, previously untreated with chemo- or immunotherapy for metastatic disease. Patients will receive Avastin (15mg/kg intravenously[IV]) on Day 1 of every 3 week cycle, in combination with fotemustine (100mg/m² IV) on Days 1, 8 and 15, followed by 4 weeks rest, followed by 100mg/m² IV every 3 weeks for 4-6 cycles. The anticipated time on study treatment is until disease progression, and the target sample size is <100 individuals.


Eligibility: Inclusion Criteria:
  -  cutaneous malignant melanoma;
  -  advanced, inoperable stage IV melanoma;
  -  measurable and/or evaluable sites of metastases.
  Exclusion Criteria:
  -  prior chemotherapy and/or IFN/IL2 based immunotherapy for metastatic disease;
  -  prior malignancies within past 5 years, with the exception of cured non-melanoma skin cancer, or in situ cancer of cervix;
  -  clinically significant cardiovascular disease;
  -  ongoing treatment with aspirin (>325mg/day) or other medications known to predispose to gastrointestinal ulceration.

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

Clinical trial: Study of Nilotinib in Metastatic Melanoma With KIT Aberrations

Summary: Major response was observed to imatinib mesylate in KIT-mutated metastatic rectal melanoma (Hodi FS et al, J Clin Oncol 26:2046-2051, 2008). In the ASCO annual meeting in 2009ar, KIT mutations were reported to be present in 23% of acral and 15.2% of mucosal melanomas (Heinrich MC et al, J Clin Oncol 26:2008 abstr 9016). Nilotinib is a novel tyrosine kinase inhibitor (TKI) targeting KIT, PDGFR, and Bcr-Abl and inhibiting the proliferating of both imatinib-sensitive and imatinib-resistant cells in vitro. Phase I study of nilotinib alone and in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors (GIST) demonstrated significant activity (72% stable disease for nilotinib alone and 56% for nilotinib/imatinib combination) (Blay JY et al, J Clin Oncol 26:2008, abstr 10553).
  Thus, we propose to conduct a phase II study of nilotinib in metastatic melanoma with KIT mutations.


Eligibility: Inclusion Criteria:
  1. Histologically or cytologically proven melanoma with stage IV or unresectable stage III disease
  2. Documented KIT aberration
  3. Adequate organ function as defined by the following criteria:
  -  Serum aspartate transaminase (AST); serum glutamic oxaloacetic transaminase (SGOT)) and serum alanine transaminase (ALT); serum glutamic pyruvic transaminase (SGPT)) ≤ 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy
  -  Total serum bilirubin ≤ 1.5 x ULN
  -  Absolute neutrophil count (ANC) ≥ 1500/µL
  -  Platelets ≥ 100,000/µL
  -  Hemoglobin ≥ 9.0 g/dL (may be transfused or erythropoietin treated)
  -  Serum calcium ≤ 12.0 mg/dL
  -  Serum creatinine ≤ 1.5 x ULN
  4. Patients with CNS metastasis must have stable neurologic function without evidence of CNS progression within 8 weeks
  5. May have previous adjuvant therapy with interferon, vaccines or therapy with IL-2, chemotherapy
  6. At least one measurable lesion by RECIST criteria
  7. ECOG PS 0-2
  Exclusion Criteria:
  1. Major surgery or radiation therapy within 4 weeks of starting the study treatment.
  2. History of or known carcinomatous meningitis, or evidence of symptomatic leptomeningeal disease on screening CT or MRI scan.
  3. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2.
  4. QTc > 470 msec on baseline EKG.
  5. Pregnancy or breastfeeding.

Relevance to patient case: not relevant