araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 40-year-old female with thyroid cancer; genetic feature: BRAF

Clinical trial: A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of of GSK2118436 in Japanese Subjects With BRAF Mutation Positive Solid Tumors

Summary: BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule.

Detailed description: BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule. Dose escalation of GSK2118436 will be performed according to a standard 3+3 dose-escalation design. GSK2118436 is given twice a day. However, to characterize the PK of GSK2118436 and its metabolites after single-dose administration, GSK2118436 will NOT be administrated for a week after the first administration. GSK2118436 continuous dosing will start after the 168-hour PK sample is obtained. Subjects may receive study treatment until disease progression, death or an unacceptable adverse event.

Eligibility: Inclusion Criteria:
  -  Histologically or cytologically confirmed diagnosis of a solid tumor that is not responsive to standard therapies or for which there is no approved or curative therapy.
  -  Subjects must have BRAF V600E or K mutant positive tumors.
  -  Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 4 weeks after the last dose of study medication.
  -  Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 16 weeks after the last dose of study medication.
  -  Must have adequate organ function.
  -  Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  Exclusion Criteria:
  -  Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy or surgery).
  -  Use of an investigational anti-cancer drug within 28 days preceding the first dose of GSK2118436.
  -  A history of other malignancy. Subjects who have been disease-free for 5 years or subjects with a history of complete resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  -  History of Human Immunodeficiency Virus (HIV) infection.
  -  Certain cardiac abnormalities.
  -  Pregnant or lactating female.

Relevance to patient case: possibly relevant
Patient case: 40-year-old female with thyroid cancer; genetic feature: BRAF

Clinical trial: A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

Summary: This is a two-arm, double-blinded, randomized, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to dabrafenib administered with a trametinib placebo (dabrafenib monotherapy). Subjects with histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible although prior systemic treatment in the adjuvant setting will be allowed. Approximately 340 subjects will be randomized 1:1 (combination therapy: dabrafenib monotherapy). Subjects will be stratified by lactate dehydrogenase (LDH) level (> the upper limit of normal (ULN) versus less than or equal to the ULN) and BRAF mutation (V600E versus V600K). The primary endpoint is investigator-assessed, progression-free survival for subjects receiving the combination therapy compared with those receiving dabrafenib monotherapy. Subjects will be followed for overall survival; crossover will not be permitted.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive using the bioMerieux (bMx) investigational use only (IUO) THxID BRAF Assay (IDE: G120011). The assay will be conducted by a central reference laboratory. Subjects with ocular or mucosal melanoma are not eligible.
  -  The subject must have a radiologically measurable tumor
  -  The subject is able to carry out daily life activities without significant difficulty (ECOG performance status score of 0 or 1).
  -  Able to swallow and retain oral medication
  -  Sexually active subjects must use acceptable methods of contraception during the course of the study
  -  Adequate organ system function and blood counts
  Exclusion Criteria:
  -  Prior treatment with a BRAF or a MEK inhibitor
  -  Prior systemic anti-cancer treatment for Stage IIIC (unresectable) or Stage IV (metastatic) melanoma. Prior systemic treatment in the adjuvant setting is allowed. (Note: Ipilimumab treatment must end at least 8 weeks prior to randomization.)
  -  The subject has received major surgery or certain tyes of cancer therapy with 21 days of starting treatment
  -  Current use of prohibited medication listed in the protocol
  -  Left ventricular ejection fraction less than the lower limit of normal
  -  Uncontrolled blood pressurl
  -  History or current evidence of retinal vein occlusion or central serous retinopathy
  -  Brain metastases unless previously treated with surgery or stereotactic radiosurgery and the disease has been stable for at least 12 weeks
  -  The subject is pregnant or nursing

Relevance to patient case: not relevant
Patient case: 40-year-old female with thyroid cancer; genetic feature: BRAF

Clinical trial: Mutation Analysis and Copy Number Changes of KRAS and BRAF Gene in Taiwanese Cases of Biliary Tact Adenocarcinoma

Summary: Cholangiocarcinoma is a fatal malignant neoplasm originating from biliary tracts and constitutes about 5-10% of primary liver cancers, characterized by a poor prognosis. High prevalence in southeast and eastern Asia has been observed. At present, the cellular and molecular mechanisms leading to oncogenesis of cholangiocarcinoma remain unclear.
  The RAS gene product has a key role in controlling cell growth and differentiation through its intrinsic GTPase activity. Point mutations that activate the RAS protein and its downstream cascade have been observed in human tumors. Both KRAS and BRAF are members of the RAS-RAF-MEK-ERK-MAP kinase pathway which mediates cellular response to growth signals. Somatic KRAS mutations are found at high rates in leukemia, colon cancer, pancreatic cancer and lung cancer. Studies from European and Japanese groups have recently described that activating KRAS/ BRAF mutations may play a role in the carcinogenesis of cholangiocarcinoma of the biliary tracts, but our preliminary data demonstrated low frequency of KRAS and BRAF mutation in the same tumor as well as the results from Thailand. In this study, the investigators hypothesize copy number changes rather than genetic mutation of either KRAS or BRAF genes may be the key findings of Taiwanese cases of the adenocarcinoma from the biliary tracts.


Eligibility: Inclusion Criteria:
  -  The patients diagnosed as biliary tact adenocarcinoma.

Relevance to patient case: not relevant
Patient case: 40-year-old female with thyroid cancer; genetic feature: BRAF

Clinical trial: Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma

Summary: This is a two-arm, open-label, randomised, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to vemurafenib. Subjects with histologically confirmed cutaneous melanoma that is either stage IIIc (unresectable) or stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible although prior systemic treatment in the adjuvant setting will be allowed. Approximately 694 subjects will be randomised 1:1 (combination therapy:vemurafenib). The primary endpoint is overall survival (OS) for subjects receiving the combination therapy compared with those receiving vemurafenib.


Eligibility: Inclusion Criteria:
  -  >= 18 years of age
  -  Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma
  -  Measurable disease according to RECIST 1.1
  -  Women of childbearing potential with negative serum pregnancy test prior to randomisation
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  -  Adequate baseline organ function
  Exclusion Criteria:
  -  Any prior use of a BRAF or MEK inhibitor
  -  Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed
  -  History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer)
  -  Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed)
  -  Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation
  -  History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy)
  -  History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Relevance to patient case: not relevant
Patient case: 40-year-old female with thyroid cancer; genetic feature: BRAF

Clinical trial: Leptin Levels in Papillary Thyroid Cancer

Summary: The purpose of this study is to evaluate Leptin levels in females, in the setting of papillary thyroid cancer, benign thyroid nodules, and in normal females without thyroid disease.

Detailed description: There will be three groups in this study, but 2 of the groups are part of another study so will only recruit normal controls.

Eligibility: Inclusion Criteria:
  -  Female
  -  Age>/- 19
  -  Not currently pregnant or lactating
  -  Normal thyroid gland by history
  Exclusion Criteria:
  -  Male Gender
  -  Pregnancy
  -  Lactation
  -  Age below 19
  -  Abnormal thyroid gland by history
  -  Abnormal thyroid gland by structure using ultrasound
  -  Abnormal thyroid gland by function using TSH, Free T4

Relevance to patient case: not relevant
Patient case: 40-year-old female with thyroid cancer; genetic feature: BRAF

Clinical trial: Impact of BRAFV600E Intratumor Heterogeneity in Thyroid Cancer Treated With Tyrosine Kinase Inhibitors

Summary: -  Background: BRAFV600E is the most frequent oncogene in differentiated thyroid cancer (DTC) occurring in about 50% of cases. Clinical trials with tyrosine kinase inhibitors (TKI) with specific activity against BRAF in metastatic radioiodine-resistant DTC (MRR-DTC) are ongoing. Very recently it has been demonstrated that DTC often consists of a mixture of tumor cells with wild-type and mutant BRAF. The subclonal occurrence of BRAFV600E in MRR-DTC could disable the therapy with BRAF targeted TKI and be responsible of the frequent defeats of this treatment. A therapeutic strategy based upon BRAF inhibitors in tumors bearing subclonal BRAFV600E could be initially successful hitting the tumor cells expressing the oncogene, and after the initial tumor growth arrest and/or shrinkage, the oncogene negative cells insensitive or less sensitive to the treatment, could restart the growth of the tumor causing the progression of the disease and the escape from the clinical response.
  -  Aims: To determine the impact of subclonal BRAFV600E on the efficacy of BRAF inhibitors in the treatment of MRR-DTC.
  -  Study design: Primary tumor tissues will be analyzed for the presence of BRAFV600E by pyrosequencing or other quantitative assay. If available, synchronous metastases and post-therapy metachronous metastases will be analyzed as well. The clinical response will be determined according to RECIST, and the association with the percentage of BRAFV600E alleles will be evaluated. Attention will be paid to the possible difference of BRAFwild-type/BRAFV600E ratio between primary tumors and synchronous metastases, primary tumors and post-therapy metachronous metastases, and between responsive and resistant synchronous tumor lesions.


Eligibility: Inclusion Criteria:
  -  subjects any sex any age with metastatic or unresectable thyroid carcinoma treated with tyrosine kinase inhibitors
  -  evidence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST)
  -  availability of study end points including best response, duration of response, and time to disease progression (based on RECIST), clinical progression, or death
  -  availability of tumor tissue samples, frozen or formaldehyde fixed-paraffin embedded from block, genomic DNA already extracted from tumor tissue
  Exclusion Criteria:
  -  concurrent Hashimoto's thyroiditis

Relevance to patient case: definitely relevant
Patient case: 40-year-old female with thyroid cancer; genetic feature: BRAF

Clinical trial: Effects of Thyroid Hormone Withdrawal on Metabolic Parameters During Radioactive Iodine Therapy in Thyroid Cancer

Summary: 1. The incidence of differentiated thyroid cancer is increasing in Korea. A significant number of them experience severe hypothyroidism in preparation for radioactive iodine (RAI) therapy after total thyroidectomy.
  2. Because the function of thyroid hormone is closely linked with lipid and glucose metabolism, overt hypothyroidism after thyroid hormone withdrawal during RAI therapy may induce the changes of metabolic parameters.
  3. We investigate the effects of thyroid hormone withdrawal on metabolic and cardiovascular parameters during radioactive iodine therapy in differentiated thyroid cancer.

Detailed description: 1. Study design measurement of various parameters during hypothyroid state (before 1 month, the day and after 1 month of RAI therapy)
  2. Measurements
  1. Measurement of metabolic and cardiovascular parameters
  -  glucose profiles : HbA1c, fasting glucose level
  -  lipid profiles : free fatty acid, total, LDL-, HDL-, cholesterol, triglyceride
  -  adipocytokines : retinol binding protein(RBP)
  -  4, leptin, resistin, adiponectin
  -  markers of endothelial and cardiac function : high-sensitivity C-reactive protein(hsCRP), homocystein, B-type natriuretic peptide(BNP)
  -  bone turnover markers : CTX, bone ALP
  2. Scoring of symptoms and signs of hypothyroidism (Zulewski score)
  -  symptoms
  -  physical signs

Eligibility: Inclusion Criteria:
  -  radioiodine therapy after total thyroidectomy in differentiated thyroid cancer
  -  age over 18
  Exclusion Criteria:
  -  kidney failure, liver failure, heart failure
  -  infection
  -  inflammation
  -  autoimmune disease
  -  other chronic disease

Relevance to patient case: not relevant
Patient case: 40-year-old female with thyroid cancer; genetic feature: BRAF

Clinical trial: Shear Wave Ultrasound Elastography in Noninvasive Diagnosis of Thyroid Nodules

Summary: Shear wave ultrasound elastography is a new technique of finding the softness or hardness in tissue by applying a "push" generated by the machine. This technique will help in diagnosing malignancy in the thyroid gland without biopsy and avoiding biopsy in noncancerous nodules.

Detailed description: Thyroid nodules are a common medical problem. With the wide use of various imaging modalities, incidentally detected thyroid nodules are becoming more common. However most of these nodules are benign with only a small proportion of 5-10% being malignant. With the increasing number of nodules detected, evaluation of these thyroid nodules presents a diagnostic challenge since the imaging modality used for evaluation at present, i.e., ultrasound (US) alone, has a low specificity of approximately 50-70%. In order to improve specificity to confidently diagnose malignancy in the thyroid nodule, a fine needle aspiration (FNA) biopsy is performed.
  In recent years, US elastography has been shown to have high specificity of 90- 98% in various studies in differentiating between benign and malignant nodules. US elastography works on the principle of detecting the stiffness within a tissue by applying compression which can be manual compression or by generation of a remote radiation force by focused ultrasonic beams called as shear waves. Shear Wave Ultrasound (SWUS) elastography is an objective method of US elastography that detects the stiffness within the nodule since the strength of the shear wave generated is known and can be controlled. SWUS elastography has shown promise in being able to noninvasively diagnose papillary carcinoma in previous studies involving preoperative patients.
  The investigators propose to perform a study to investigate the efficacy of SWUS elastography in diagnosing malignant thyroid nodules and noninvasively decreasing the number of FNAs performed by avoiding FNA in benign nodules. The Investigators will enroll patients with thyroid nodules before they undergo FNA biopsy or surgery. We also propose to compare routine US and SWUS elastography and their combined use in differentiating malignant from benign nodules. The investigators hypothesize that SWUS elastography can be used as a noninvasive screening tool, prior to an FNA, to screen out benign and malignant nodules with high level of confidence and reduce the number of biopsies in the future.

Eligibility: Inclusion Criteria:
  -  Clinical diagnosis of thyroid nodule
  -  Referred for thyroid FNA or surgery
  Exclusion Criteria:
  -  Minors; age <18
  -  Unable to provide informed consent

Relevance to patient case: not relevant
Patient case: 40-year-old female with thyroid cancer; genetic feature: BRAF

Clinical trial: A Pharmacokinetics Study to Investigate the Effect of Vemurafenib on Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Melanoma

Summary: This open-label, multi-center, three-period, one sequence study will investigate the effect of vemurafenib on the pharmacokinetics of digoxin in patients with unresectable BRAFV600-mutation positive metastatic melanoma or other malignant tumor type that harbors a V600-activating mutation of BRAF without acceptable standard treatment options. Patients will receive multiple doses of vemurafenib in Periods B and C and a single dose of digoxin in Periods A and C. Eligible patients will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764). The anticipated time on study treatment is approximately 36 days.


Eligibility: Inclusion Criteria:
  -  Male or female patients >= 18 years old
  -  Patients with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a DNA sequencing method, and who have no acceptable standard treatment options
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  -  Life expectancy >= 12 weeks
  -  Full recovery from the effects of any major surgery or significant traumatic injury within 14 days prior to the first dose of study treatment
  -  Adequate hematologic and end organ function
  -  Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two effective methods of contraception
  -  Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential
  Exclusion Criteria:
  -  Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drug
  -  Prior anti-cancer therapy within 28 days before the first dose of study drug
  -  History of clinically significant cardiac or pulmonary dysfunction
  -  History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment
  -  History of myocardial infarction within 6 months prior to first dose of study drug
  -  Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living
  -  History of congenital long QT syndrome or QTc > 450 ms
  -  Current digoxin therapy or anticipated requirement to take digoxin therapy during the study
  -  Active central nervous system lesions
  -  Uncontrolled or poorly controlled diabetes
  -  Current severe, uncontrolled systemic disease

Relevance to patient case: not relevant