araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Safety, Pharmacokinetics and Pharmacodynamics of BEZ235 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 RP2D of the orally administered PI3K/mTOR inhibitor BEZ235 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with EGFR mutant 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 BEZ235 and MEK162.
  Study drugs will be administered orally on a continuous schedule, MEK162 bid and BEZ235 qd, 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 1.0
  Exclusion Criteria:
  -  Patients with primary CNS tumor or CNS tumor involvement
  -  Diabetes mellitus - Unacceptable ocular/retinal conditions
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: MEK162 and RAF265 in Adult Patients With Advanced Solid Tumors Harboring RAS or BRAFV600E Mutations

Summary: This is a multi- center, open-label, dose finding, Phase Ib study to be conducted in two stages: a dose escalation part to determine the maximum tolerated dose (MTD) safety and tolerability of concurrent administration of MEK162 and RAF265, followed by an expansion part to further assess the safety and preliminary anti-tumor efficacy of this oral combination within two separate patient populations: i) patients with advanced solid tumors harboring BRAFV600E mutations or ii) patients with advanced solid tumors harboring RAS mutations.


Eligibility: Inclusion Criteria:
  Patients with histologically or cytologically confirmed and non-resectable advanced solid tumors for which no further effective standard therapy exists.
  -  The patients' tumors must contain documented activating somatic BRAFV600E* , NRAS or KRAS mutations (except for pancreatic cancer)
  -  All patients enrolled MUST provide fresh or archival tumor samples at baseline to enable central confirmation of BRAF or KRAS/NRAS mutations
  -  Measurable, or non-measurable but evaluable disease as determined by RECIST
  -  Adequate bone marrow function
  -  Adequate hepatic and renal function
  -  Adequate cardiovascular function
  -  Negative serum β HCG test (female patients of childbearing potential only) within 72 hrs prior to first dose
  Exclusion Criteria:
  -  Patients with a history of primary central nervous system tumors or brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases
  -  Current evidence of retinal disease; or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO (e.g., optic disc cupping, visual field defects, IOP > 21 mm Hg)
  -  Impaired cardio-/vascular function or clinically significant cardiovascular diseases, including any of the following:
  -  History/evidence of acute coronary syndromes (including MI, unstable angina, CABG, coronary angioplasty, or stenting) ≤ 6 months prior to starting study drugs
  -  Thromboembolic event (DVT, CVA, PE) ≤ 6 months prior to starting study
  -  Symptomatic CHF, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality
  -  Uncontrolled arterial hypertension, defined as BP > 140/100 mmHg (average of 3 consecutive readings)
  -  History of melena, hematemesis or hemoptysis within the last 3 months
  -  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)
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

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: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Evaluation of Carboplatin/Paclitaxel With and Without Trastuzumab (Herceptin) in Uterine Serous Cancer

Summary: The primary objective of this study is to estimate whether the addition of trastuzumab to paclitaxel and carboplatin chemotherapy improves progression free survival when compared to paclitaxel and carboplatin alone in Uterine Serous Papillary Carcinoma (USPC) patients overexpressing Her2/neu at 3+ level by immunohistochemistry (IHC)or positive by fluorescence in situ hybridization (FISH).

Detailed description: The purpose of this study is to perform a randomized Phase II evaluation of Carboplatin/Paclitaxel with or without Trastuzumab (Herceptin) in patients with HER2/neu+ advanced stage/recurrent disease with an emphasis on determining the progression free survival in USPC patients and assessing immunologic markers predictive of trastuzumab response.

Eligibility: Inclusion Criteria:
  -  Patients must have advanced (stage III-IV) or recurrent histologically confirmed USPC with measurable disease.
  -  Patients must harbor a tumor HER2/neu+ based upon IHC staining score of 3+ or 2+ with confirmed gene amplification by FISH
  Exclusion Criteria:
  -  Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancers, significant history of cardiac disease, uncontrolled hypertension, unstable medical issue, brain leptomeningeal, prior therapy with trastuzumab, uncontrolled seizure disorder, seropositive for HIV, active hepatitis, hemorrhagic diathesis or requiring supplemental oxygen.

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Comparison of Survival Benefit of Panitumumab With Supportive Care to Best Supportive Care Alone in Patients With Metastatic Colorectal Cancer

Summary: The purpose of this study is to evaluate the benefit of panitumumab in addition to best supportive care compared to best supportive care alone in patients with chemorefractory wild-type KRAS (Kirsten rat sarcoma viral oncogene homolog) metastatic colorectal cancer.


Eligibility: Inclusion Criteria:
  -  Diagnosis of metastatic colorectal cancer (CRC)
  -  Wild-type (without mutation in codons 12 and 13) KRAS gene in tumor tissue confirmed by a central laboratory
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  -  At least 1 measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines.
  -  Treatment failure (defined as failure due to either disease progression [clinical or radiological] or toxicity [treatment intolerance]) of a prior regimen containing irinotecan for metastatic disease and a prior regimen containing oxaliplatin for metastatic disease. Oxaliplatin and irinotecan may have been administered sequentially or in combination.
  -  Disease relapse within 6 months after completing adjuvant chemotherapy (with either an irinotecan or oxaliplatin containing regimen) will also be considered as treatment failure of a prior regimen for metastatic disease
  -  Must have previously received a thymidylate synthase inhibitor (eg, fluorouracil, capecitabine, raltitrexed, or fluorouracil-uracil) at any point for treatment of CRC
  -  Man or woman at least 18 years of age
  -  Adequate hematologic, renal, hepatic and metabolic function
  -  Negative pregnancy test within 72 hours before randomization (for women of childbearing potential only)
  -  Subject or subject's legally acceptable representative has provided informed consent.
  -  Other protocol-specified criteria may apply
  Exclusion Criteria:
  -  Symptomatic brain metastases requiring treatment
  -  History of another primary cancer within 5 years of randomization
  -  Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (eg, panitumumab or cetuximab) or treatment with small molecule EGFR inhibitors (eg, gefitinib, erlotinib, lapatinib)
  -  Antitumor therapy (eg, chemotherapy, hormonal therapy, immunotherapy, antibody therapy) within 21 days before randomization
  -  Radiotherapy within 14 days before randomization.
  -  Exclusion Criteria for corrected QT (QTc) Evaluation Subpart of the Study: Prolongation of QT/QTc interval > 450 milliseconds at screening
  -  Other protocol-specified criteria may apply

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

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: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Assessing the Clinical Effectiveness of Serum Biomarkers in the Diagnosis of Metastatic Uveal Melanoma

Summary: Uveal melanoma is the most common primary intraocular tumor in adults. The local treatment is effective, but patients still die of metastatic disease. It has been shown that early diagnosis of a few isolated metastases can result in a clean surgical excision of the metastases and an extension of the expected survival from 7-12 months to over 10 years on some patients.
  Many serum biomarkers are employed in Oncology. It makes sense to try the relevant ones in the diagnosis of metastatic uveal melanoma.
  The investigators hypothesis is that a soluble serum biomarker level changes upon development of metastatic disease either by secretion by the tumor cells themselves or by their environment. Detection of changes in biomarker level may lead to the diagnosis of metastases before they can be detected by imaging modalities, thus allowing for early treatment of the metastases and a better chance of success.


Eligibility: Inclusion Criteria:
  -  diagnosis of uveal melanoma
  Exclusion Criteria:
  -  refusal to participate in the study

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

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: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

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: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Trial of pIL-12 Electroporation Malignant Melanoma

Summary: This study will assess the safety and effectiveness of intratumoral plasmid interleukin-12 DNA injection (pIL-12) with electroporation (EP) in malignant melanoma. Intratumoral pIL-12 EP is a gene therapy approach to directly induce a pro-inflammatory response within a tumor to initiate and/or enhance anti-tumor immunity.

Detailed description: Plasmid IL-12 (pIL-12) at a concentration of 0.5 mg/mL will be injected intratumorally at a dose volume of ¼ of the calculated lesion volume and a dose volume per lesion of 0.1 mL for lesions of volume < 0.4 cm3. Six pulses at field strengths of (E+) of 1500 V/cm and pulse width of 100 μs at 1-second intervals will be administered using the OMS to each previously injected tumor.
  Two treatment regimens will be explored:
  Regimen A: Treatment on Days 1, 8 and 15 every 6 weeks Regimen B: Treatment on Days 1, 5 and 8 every 6 weeks. Lesions will be treated on either Regimen A or Regimen B. Subsequent cycles may be given at 6-week intervals, for up to 9 treatment cycles in total.

Eligibility: Inclusion Criteria:
  -  Patients with advanced cutaneous or subcutaneous in-transit or metastatic melanoma
  -  Age ≥ 18 years of age
  -  ECOG performance status 0-2
  -  Patients may have had prior chemotherapy or immunotherapy (vaccines, interferon, ipilimumab, or IL-2) with progression or persistent disease
  -  Patients may have had radiation therapy, but must have progressive disease after radiation therapy if the lesions to be treated are within the radiation field
  -  Female patient of childbearing potential has a negative pregnancy test within 14 days prior to the start of study drug
  -  Adequate organ function
  -  Able to give informed consent
  Exclusion Criteria:
  -  Prior therapy with IL-12 or prior gene therapy
  -  Concurrent immunotherapy, chemotherapy, or radiation therapy for duration of subject participation on study
  -  Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study enrollment
  -  Pregnant or breast-feeding women
  -  Patients with electronic pacemakers or defibrillators are excluded from this study
  -  The patient is known to be positive for Human Immunodeficiency Virus (HIV) or has another confirmed or suspected immunosuppressive or immunodeficient condition (patients with thyroiditis are eligible)
  -  Life expectancy of less than 6 months
  -  History of significant cardiovascular disease (i.e. NYHA class 3 congestive heart failure; myocardial infarction with the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias)
  -  Other clinically significant co-morbidities such as uncontrolled pulmonary disease, uncontrolled diabetes, active CNS disease, active infection or any other condition that could compromise the patients participation in the study according to the investigator

Relevance to patient case: not relevant
Patient case: 55-year-old male with Melanoma. Genetic variant: NRAS (Q61K). Other conditions: Hypertension.

Clinical trial: Metronomic Therapy in Patients With Metastatic Melanoma

Summary: SUMMARY: Metronomic Therapy in Patients with Metastatic Melanoma: A Phase II Study of Low Dose Vinblastine, Cyclophosphamide, and Dacarbazine.
  Patients with measurable metastatic melanoma are eligible. All patients will be treated as outlined below with combined vinblastine, cyclophosphamide, and dacarbazine. Patients will be treated continuously, until evidence of progression of disease, or for up to two cycles following disappearance of all disease. A cycle will be defined as three weeks of continuous therapy with a one week rest.

Detailed description: Low dose continuous chemotherapy, called metronomic chemotherapy, is designed to target vascular cells and inhibit tumor growth and metastasises. A recent study in a melanoma mouse model has identified low dose vinblastine, cyclophosphamide and dacarbazine as a treatment which improves the animal's survival and is superior to full dose dacarbazine alone. This clinical trial seeks to translate this laboratory model directly into metastatic melanoma patients.

Eligibility: -  Metastatic melanoma with measurable disease
  -  Patients must be at least 4 weeks from their last immunotherapy, radiation, surgery or chemotherapy (6 weeks for nitrosoureas) and recovered from all ill
  -  Karnofsky Performance Status ≥60%
  -  Life expectancy ≥ twelve weeks
  -  Adequate end organ function
  -  Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study.
  -  Appropriate Contraception in both sexes
  -  The patient must be competent and signed informed consent.
  EXCLUSION CRITERIA
  -  Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence, breast CIS.
  -  In patients with a prior history of invasive malignancy, less than five years in complete remission.
  -  Have evidence of significant co-morbid illness such as uncontrolled diabetes - Uncontrolled brain metastasis: Patients with brain metastasis most have been treated with brain radiation therapy or surgery and remain clinically stable for a minimum of 4 weeks.

Relevance to patient case: not relevant