araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

Clinical trial: Safety, Pharmacokinetics and Pharmacodynamics of BKM120 Plus MEK162 in Selected Advanced Solid Tumor Patients

Summary: This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of the orally administered phosphatidylinositol 3'-kinase (PI3K) inhibitor BKM120 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) which has progressed on EGFR inhibitors and triple negative breast cancer, as well as pancreatic cancer, colorectal cancer, malignant melanoma, NSCLC, and other advanced solid tumors with KRAS, NRAS, and/or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RP2D, two expansion arms will be opened in order to further assess safety and preliminary anti-tumor activity of the combination of BKM120 and MEK162.
  Study drugs will be administered once daily orally on a continuous schedule. A treatment cycle is defined as 28 days.


Eligibility: Inclusion Criteria:
  -  Histologically/ cytologically confirmed, advanced non resectable solid tumors
  -  Measurable or non-measurable, but evaluable disease as determined by RECIST
  Exclusion Criteria:
  -  Patients with primary CNS tumor or CNS tumor involvement.
  -  Diabetes mellitus
  -  Unacceptable ocular/retinal conditions

Relevance to patient case: possibly relevant
Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

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: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

Clinical trial: miRNA Machinery in Melanoma, Melanoma Metastases and Benign Melanocytic Naevi

Summary: MicroRNAs (miRNAs) are very small endogenous RNA molecules about 22-25 nucleotides in length, capable of post-transcriptional gene regulation. miRNAs bind to their target messenger RNAs (mRNAs), leading to cleavage or suppression of target mRNA translation based on the degree of complementarity. miRNAs have recently been shown to play pivotal roles in diverse developmental and cellular processes and linked to a variety of skin diseases and cancers. In the present study, the investigators examines the expression profiles of miRNA machinery components such as miRNA maturation and transport factors, microprocessor complex and RISC subunits in cutaneous melanoma, cutaneous melanoma metastases and benign melanocytic nevi.

Detailed description: Patients with cutaneous melanoma, cutaneous melanoma metastases and benign melanocytic nevi were included in the study. Punch biopsies were harvested from the center of the tumors. The miRNA machinery components were detected by quantitative real-time reverse transcriptase polymerase chain reaction.

Eligibility: Inclusion Criteria:
  -  cutaneous melanoma
  -  cutaneous melanoma metastases
  -  benign melanocytic nevi
  Exclusion Criteria:
  -  other forms of malignancy

Relevance to patient case: not relevant
Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

Clinical trial: Weight Maintenance Through Physical Activity and Social Support in Rural Middle-Aged Women

Summary: The purpose of this study is to compare an technology-based weight maintenance intervention using action plans, videos discussion boards and health behavior tracking (weight, calories in and out, pedometer steps) with a technology-based standard advice group to facilitate health management, resourcefulness and health status for rural middle-aged women.

Detailed description: The purpose of this research project is to evaluate the influence of a theory-based intervention using the Health Effects of Life Transitions for Women Model to promote maintenance of initial weight loss. The intervention will be designed to promote physical activity to prevent weight regain among an underserved and vulnerable population of rural, mid-life women. The intervention delivered through action plans, videos, discussion boards and health behavior tracking (weight, calories in and out, pedometer steps) to facilitate health management, resourcefulness and health status will be compared with the standard advice group who receives newsletters and health behavior tracking (weight) to initiate, increase, or sustain physical activity for weight maintenance.

Eligibility: Inclusion Criteria:
  Women:
  -  aged 40-64 years;
  -  reported intentional weight loss of 5-10% of initial body weight within previous 6 months;
  -  residing in a rural county (population < 50,000 residents) or rural community (population less than 2,500) within driving distance of a UNMC College of Nursing campus;
  -  ability to communicate in English (verbal and written);
  -  ambulatory and can walk at least one block without the use of an assistive device, such as a cane, walker, or wheelchair;
  -  have access to the internet and current email account; and
  -  answer 'no' to all questions on the Physical Activity Readiness Questionnaire (PAR-Q) or obtain clearance from their physician to become more active.
  Exclusion Criteria:
  -  instructed by a physician not to exercise;
  -  presence of chest pain, shortness of breath, or feelings of light-headedness upon exertion.

Relevance to patient case: not relevant
Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

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: definitely relevant
Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

Clinical trial: Clinical and Histopathologic Characteristics of BAP1 Mutations

Summary: The goal of this protocol is to determine the prevalence of somatic and germline mutations in BAP1 (BRCA associated protein-1) among patients with mesothelioma , choroidal nevus, primary uveal melanoma (UM), or metastatic UM seen at our institution.


Eligibility: Inclusion Criteria:
  All consents:
  -  > or = to 18 years of age
  -  Ability to provide informed consent
  Consent 1:
  Mesothelioma
  -  Histologically proven diagnosis of Mesothelioma OR Choroidal nevus
  -  Diagnosis of choroidal nevus by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography OR Primary uveal melanoma
  -  Diagnosis of uveal melanoma by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography
  Consent 2:
  Mesothelioma
  -  Histologically proven diagnosis of Mesothelioma AND
  -  BAP1 mutation or loss of expression identified in tumor sample
  OR one of the following:
  -  Age<50 at diagnosis
  -  No history of asbestos exposure
  -  Personal history of choroidal nevus, uveal melanoma, melanoma, renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  -  History of malignancy in more than two first-degree relatives OR Choroidal nevus
  -  Diagnosis of choroidal nevus by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography AND one of the following:
  -  More than one clinical risk factor, which may include: orange pigment, thickness > 1 < 2.5mm
  -  Personal history of uveal melanoma, skin melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma OR Primary uveal melanoma
  -  Diagnosis of uveal melanoma by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography
  AND one of the following:
  -  Personal history of uveal melanoma, skin melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  -  History of malignancy in more than two first-degree relatives OR Metastatic uveal melanoma
  -  Histologically proven diagnosis of metastatic uveal melanoma AND
  -  BAP1 mutation or loss of expression identified in tumor sample
  OR one of the following:
  -  Personal history of uveal melanoma, skin melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  -  History of malignancy in more than two first-degree relatives
  Consent 3:
  -  Relative of patient with germline BAP1 mutation identified through identified testing
  Exclusion Criteria:

Relevance to patient case: not relevant
Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

Clinical trial: A Phase 2 Study of Panitumumab in Patients With Cetuximab-refractory Metastatic Colorectal Cancer

Summary: The purpose of this study is to assess if panitumumab is active enough to warrant comparative studies in patients with metastatic colorectal cancer that has progressed after treatment with cetuximab.

Detailed description: The study was amended with modification of inclusion criteria (from wild-type tumor KRAS gene to wild-type RAS gene, including KRAS and NRAS exons 2, 3 and 4)
  RAS mutational status of tumors of patients enrolled before amendment 1 approval will be centrally revised. Patients whose tumors will result RAS mutated at the biomarkers central revision, will be replaced. Therefore, the overall sample size at both the stages may be higher than the one initially planned.

Eligibility: Inclusion Criteria:
  -  Pathologic diagnosis of metastatic colorectal adenocarcinoma
  -  a wild-type RAS tumor (mutational status has to be determined by an experienced laboratory using validated test methods for detection of KRAS exons 2, 3, and 4, and NRAS exons 2, 3, and 4
  -  Failure from previous treatment with fluoropyrimidine, oxaliplatin and irinotecan. Patients may or may not have been treated with bevacizumab.
  -  Documented disease progression following a treatment with cetuximab in patients who showed either an objective response after 8 weeks or stable disease after 16 weeks of cetuximab treatment.
  -  Age at least 18 years
  -  ECOG Performance Status 0-2
  -  Neutrophils at least 1,500 mm3, platelets at least 100,000 mm3, and hemoglobin at least 9 g/dL
  -  Bilirubin level less than 1.5 times ULN
  -  AST (SGOT) and ALT (SGPT) not greater than 2.5 times ULN (or 5 times ULN in presence of liver metastasis)
  -  Serum creatinine less than 1.5 times ULN
  -  Effective contraception, if the risk of conception exists
  -  Life expectancy at least 3 months
  -  Written informed consent
  Exclusion Criteria:
  -  Symptomatic brain metastasis
  -  Interstitial pneumonitis or pulmonary fibrosis
  -  Any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or non melanoma skin cancer)
  -  Chemotherapy, radiotherapy or immunotherapy within the past 4 weeks
  -  Any unstable systemic disease (including active infections, any significant hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study drugs or render the patient at high risk from treatment complications
  -  Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment

Relevance to patient case: not relevant
Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

Clinical trial: Exercise Time in Sedentary Middle-aged Female

Summary: The exercise time is an important factor among the medical guides for weight loss; however, there is still little knowledge about exercise duration paths in middle-aged and older women. The present study aimed to determine the effects of the interval training on weight loss and lipid profile, and to compare its efficiency with the continuous training.

Detailed description: Participants included sedentary women (age 45-75 years) with overweight or obesity (n= 115). They were randomly divided into two groups including continuous exercise, and interval exercise. The weight assessment parameters including change in weight and body composition, blood sample tests were performed pre- and three month post-intervention.

Eligibility: Inclusion Criteria:
  -  Sedentary lifestyle
  -  Good Health
  -  Weight stability
  Exclusion Criteria:
  *Abnormality or history of Disease

Relevance to patient case: not relevant
Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

Clinical trial: Lymph Node Mapping Using Indocyanine Green Solution in Diagnosing Patients With Malignant Melanoma

Summary: This clinical trial studies lymph node mapping using indocyanine green solution in diagnosing patients with malignant melanoma. Diagnostic procedures, such as lymph node mapping using indocyanine green solution, may help find out how far the melanoma has spread and may help in planning cancer treatment.

Detailed description: PRIMARY OBJECTIVES:
  I. To show that indocyanine green (ICG) (indocyanine green solution) is equal to both isosulfan blue (ISB) and technetium Tc 99m sulfur colloid (TSC) and will allow all lymph node mapping to occur in the operating room (OR).
  OUTLINE:
  Patients receive peri-tumoral, intradermal injections of isosulfan blue and indocyanine green solution. During surgery, patients undergo identification of the sentinel lymph node and imaging using a laser with videocamera (SPY Elite camera).

Eligibility: Inclusion Criteria:
  -  Ability to understand and willingness to sign informed consent document
  -  Signed written informed consent
  -  Patients with malignant melanoma (MM) undergoing sentinel lymph node biopsy (SNLB)
  -  Complete blood count (CBC) and metabolic panel within 6 months
  Exclusion Criteria:
  -  History of hepatic or renal failure
  -  Allergy to iodine containing products
  -  Patients who are pregnant or may be pregnant
  -  Patients with psychiatric or addictive disorders that in the opinion of the research team, may not be able to meet study requirements

Relevance to patient case: not relevant
Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

Clinical trial: A Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer

Summary: This study will investigate whether the combination of PF-05212384 plus Irinotecan improves progression free survival in patients with KRAS and NRAS wild type metastatic colorectal cancer when compared with the combination of cetuximab plus Irinotecan. A Japanese Lead in Cohort will assess the safety of the combination of PF-05212384 + irinotecan in patients enrolled at Japanese sites.


Eligibility: Inclusion Criteria:
  -  KRAS and NRAS wild type metastatic colorectal cancer
  -  Progression following treatment for colorectal cancer with irinotecan, oxaliplatin and fluoropyrimidine therapy in the metastatic setting.
  -  Eastern Cooperative Oncology Group [ECOG] Performance Status of 0, 1, or 2
  -  At least one measurable lesion by Response Evaluation Criterion in Solid Tumors [RECIST]
  Exclusion Criteria:
  -  More than 2 prior cytotoxic chemotherapy regimens for metastatic colorectal cancer.
  -  Prior treatment with a PI3K, mTOR, AKT or EGFR inhibitor
  -  Patients who have discontinued treatment with prior irinotecan therapy due to toxicity.
  -  Prior radiation to the pelvis or abdomen
  -  Patients with history of interstitial lung disease.

Relevance to patient case: not relevant
Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

Clinical trial: Systemic Treatment Of Resistant Metastatic Disease Employing CVA21 and Pembrolizumab in Non-small Cell Lung Cancer and Bladder Cancer (STORM/ KEYNOTE-200)

Summary: The purpose of this trial is to assess the ability of CVA21, either alone (Part A) or in combination with pembrolizumab (Part B), to reach and to replicate in existing tumors (while sparing normal cells) and to establish a safe multi-dose schedule of the virus for the treatment of solid tumors where enhanced expression of ICAM-1 and/ or DAF receptor occurs.
  This trial will consist of 2 sequential parts: VLA-009 (Part A) conducted only in the UK employs CVA21 as a monotherapy in NSCLC, castrate-resistant prostate cancer, melanoma and bladder cancer. VLA-009 (Part B) conducted in the US and UK employs CVA21 with pembrolizumab in NSCLC and bladder cancer.
  Both VLA-009A and VLA-009B are open-label, multi-center, ascending dose escalation (3+3 design) dose-finding and signal-seeking studies.


Eligibility: Inclusion Criteria:
  -  Histologically-confirmed (1) NSCLC, (2) bladder cancer, (3) castrate-resistant prostate cancer which are metastatic, or (4) stage 3C or stage 4 melanoma.
  -  VLA009A: Locally advanced and/or metastatic disease for which curative surgery and/or radiation therapy is not possible and judged not to be a candidate for the current standard of care treatment. VLA009B: locally advanced and/or metastatic disease and judged to be a candidate for pembrolizumab to be used in combination with CVA21.
  -  All subjects in Cohort 3 or Phase 2 dose (P2D) must have a lesion accessible for FNA or core or open biopsy on day 8 of the first treatment cycle.
  -  No CVA21 neutralising antibody (≤ 1:16)
  -  Measurable or evaluable disease
  Exclusion Criteria:
  -  Second primary malignancy within the past 2 years (except non-melanoma skin cancer, in situ carcinoma of the cervix, breast cancer)
  -  Concurrent immunosuppressive therapy and no known immunosuppressive disease other than primary tumour

Relevance to patient case: not relevant