araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

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: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: XL999 Administered Intravenously to a Subject With Advanced Malignancies

Summary: Cancer is a worldwide clinical and economic problem. Conventional approaches to treating cancer include surgery, radiotherapy, and cytotoxic chemotherapy as single modalities or as combined therapies. Recently, targeted therapies including antibodies and small molecule inhibitors have also demonstrated clinical benefit. It is now possible to study different genetic lesions involved in cancer types due to advances in genomic methodologies. The investigational drug in this study, XL999 inhibits multiple receptor tyrosine kinases, including VEGF receptor (VEGFR2/KDR), platelet derived growth factor receptors (PDGFRβ), fms-like tyrosine kinase receptor 3 (FLT3), fibroblast growth factor receptors (FGFR1, FGFR3), RET, and KIT, and thus, interferes with multiple cellular processes simultaneously and will likely have effects on the integrity of tumor neovasculature and angiogenesis. Together with the ability to induce a novel cell cycle arrest, the spectrum of activities that XL999 exhibits may reduce both tumor cell proliferation and angiogenesis in the clinic.
  The rationale and purpose of this maintenance study is to allow a subject receiving clinical benefit from XL999 to continue treatment.


Eligibility: Inclusion Criteria:
  -  The subject is eligible to continue to receive XL999 in the absence of progressive disease and unacceptable XL999-related toxicity.
  Exclusion Criteria:
  -  Progressive disease.

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: A Phase 2 Study of BGJ398 in Patients With Recurrent GBM

Summary: This is an open-label non-randomized, multicenter, phase II study of BGJ398 administered to adult patients with histologically confirmed GBM and/or other glioma subtypes with FGFR1-TACC1, FGFR3-TACC3 fusion and/or activating mutation in FGFR1, 2 or 3.

Detailed description: Patients will be enrolled in two groups. Group 1 will enroll patients who are not candidates for surgery. Group 2 will enroll patients who are surgical candidates. Patients from both groups will be evaluated for tumor response and progression by MRI every 8 weeks until disease progression or discontinuation from study using RANO criteria.

Eligibility: Inclusion criteria:
  1. Patients with histologically confirmed GBM and/or other glioma subtypes at the time of diagnosis or prior relapse.
  2. Written documentation of local or central laboratory determination of amplification or translocation to FGFR1-TACC1, FGFR3-TACC-3 fusion and/or activating mutation in FGFR1, FGFR2,or FGFR3
  3. RANO defined tumor progression by MRI in comparison to a prior scan
  4. Patients must have received prior external beam radiotherapy and temozolomide.
  Exclusion criteria:
  1. History of another primary malignancy
  2. Prior or current treatment with a FGFR inhibitor
  3. Neurological symptoms related to underlying disease requiring increasing doses of corticosteroids
  4. Patients must not be taking Enzyme Inducing Anti-Epileptic Drug (EIAED). If previously on an EIAED, the patient must be off of it for at least two weeks prior to study treatment.

Relevance to patient case: not relevant
Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: A Study of MEHD7945A and Cobimetinib in Patients With Locally Advanced or Metastatic Cancers With Mutant KRAS

Summary: This open-label, multicenter, global Phase Ib study will evaluate the safety, tolerability and pharmacokinetics of intravenous (IV) dosing of MEHD7945A in combination with oral dosing of cobimetinib in patients with locally advanced or metastatic solid tumors that carry a Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutation and for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate. The study comprises a dose-escalation (Stage 1) and an indication-specific cohort expansion stage (Stage 2).


Eligibility: Inclusion Criteria:
  -  Locally advanced or metastatic solid KRAS-mutant tumors, for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  Evaluable disease or disease measurable per modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
  -  Consent to provide archival tumor tissue for biomarker testing
  -  Additionally, for patients who are considered for enrollment into the indication specific expansion cohorts in Stage 2, the current cancer must be either KRAS-mutant colorectal cancer (CRC) or KRAS-mutant non-small cell lung cancer (NSCLC)
  Exclusion Criteria:
  -  History of prior significant toxicity from another MEK pathway inhibitor or combination of another MEK and epidermal growth factor receptor (EGFR) inhibitor requiring discontinuation of treatment
  -  Previous treatment with a combination of a MEK inhibitor with an EGFR inhibitor (applies only to the indication specific expansion cohorts in Stage 2)
  -  Allergy or hypersensitivity to components of the cobimetinib formulations
  -  History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of therapy
  -  History of interstitial lung disease (ILD)
  -  Known severe ulcer disease
  -  History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioetinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
  Patients will be excluded if they currently have either of the following conditions which have been identified as risk factors for CSCR:
  -  Uncontrolled glaucoma with intraocular pressure greater than (>) 21 millimeters of mercury (mm Hg)
  -  Grade greater than equal to (>=) 3 hypertriglyceridemia

Relevance to patient case: not relevant
Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: Carfilzomib for the Prevention of Graft Versus Host Disease

Summary: The aim of this study is to evaluate the safety and efficacy of Carfilzumib, which is a novel biological agent used in the treatment of multiple myeloma in preventing graft-versus-host disease, after stem cells transplantation from unrelated donors.


Eligibility: Inclusion Criteria:
  1. Patients with MDS/AML
  2. 18 years or older and willing and able to comply with the protocol requirements.
  3. LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
  4. Patients undergoing 8-10/10 HLA matched unrelated and unmanipulated PBSC transplantation
  5. Patients conditioned with reduced intensity or reduced toxicity conditioning i.e. Fludarabine combine with Treosulfan or 2-4 days of I.V Busulfan.
  6. Patients must sign written informed consent.
  7. Adequate birth control in fertile patients.
  Exclusion Criteria:
  1. Patients undergoing other type of transplantation or with other type of basic disease other than AML or MDS.
  2. Patients with respiratory failure (DLCO < 30%).
  3. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention.
  4. Patients with > grade II liver renal toxicity.
  5. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate
  6. Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit
  7. Creatinine > 2.0 mg/dl
  8. ECOG-Performance status > 2
  9. Uncontrolled infection
  10. Pregnancy or lactation
  11. CNS disease involvement
  12. Pleural effusion or ascites > 1 liter.

Relevance to patient case: not relevant
Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: A Study to Assess the Efficacy and Safety of the VEGFR-FGFR Inhibitor, Lucitanib, Given to Patients With Advanced/Metastatic Lung Cancer and FGF, VEGF, or PDGF Related Genetic Alterations

Summary: The purpose of this study is to determine whether lucitanib is safe and effective in the treatment of patients with advanced/metastatic lung cancer and fibroblast growth factor (FGF), vascular endothelial growth factor receptor (VEGF), or platelet derived growth factor (PDGF) related genetic alterations.

Detailed description: Lucitanib is an oral inhibitor of the tyrosine kinase activity of FGFR 1-3, VEGFR 1-3, and PDGFR α/β. Lucitanib has demonstrated potent anti-tumor and anti-angiogenic activity in vitro proliferation assays and in vivo using human tumor xenograft models, with a trend for stronger efficacy in those with genomic aberrancies of FGF or PDGF. Abnormalities in the FGF, VEGF, and PDGF-related genes are observed across lung cancer histologies.
  The first in human trial of lucitanib demonstrated that daily lucitanib is clinically active in patients with advanced solid tumors. Specifically, patients with FGFR1-amplification appeared to derive particular benefit from lucitanib.
  Based on these results, this study is designed to explore the safety and anti-tumor activity of daily lucitanib in lung cancer patients with FGF, VEGF, and PDGF genetic alterations.

Eligibility: Inclusion Criteria:
  -  Histologically or cytologically confirmed advanced/metastatic SCLC or NSCLC
  -  Any of the following tumor tissue based genetic alterations: FGFR1, FGFR2, FGFR3, VEGFA, or PDGFRα amplification; Any FGFR1, FGFR2, or FGFR3 gene fusion; FGFR1, FGFR2, or FGFR3 activating mutation
  -  Availability of tumor tissue sample suitable for the central confirmation of the genetic alteration and exploratory analyses
  -  Eastern Cooperative Oncology Group (ECOG) of 0 or 1
  -  Measurable disease per RECIST 1.1
  -  Documented radiographic disease progression following at least one line of therapy in the advanced/metastatic setting
  Exclusion Criteria:
  -  Tumors that are invading a major vessel; NSCLC tumors abutting to a major vessel
  -  Uncontrolled hypertension, defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg with optimized anti-hypertensive therapy
  -  Uncontrolled hypothyroidism defined as serum thyroid stimulating hormone (TSH) higher than 5 mIU/mL while receiving appropriate thyroid hormone therapy
  -  Symptomatic and/or untreated central nervous system metastases
  -  Presence of another active cancer
  -  Ongoing adverse events from surgery or prior anti-cancer therapies, including radiation, targeted, or cytotoxic therapies
  -  Pregnant or breastfeeding women

Relevance to patient case: not relevant
Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: Optimized Treatment Strategy for HighGrade1 (HGT1) Bladder Cancer Based on Substaging: a Prospective Observational Cohort Study

Summary: Non-muscle invasive bladder cancer of High Grade stage T1 (HGT1), has up to 20% risk of progression to invasive disease. Because the depth of substaging seems to identify two separate groups with different progression risk (HighGradeT1a and HighGradeT1b), we design a differential treatment strategy for each group. The main hypothesis is that HighGradeT1a bladder cancer can spare a second endoscopic procedure.

Detailed description: Only cases of initial diagnosis of HighGradeT1 and with a complete transurethral endoscopic resection (TUR) of bladder tumor) can enter this protocol. HighGradeT1a will only receive standard BCG treatment (induction and maintenance). HighGradeT1b will undergo a second transurethral endoscopic resection (TUR) after the induction of Bacillus de Calmette-Guerin (BCG) and then continue mantenaince BCG and standard follow-up.

Eligibility: Inclusion Criteria:
  -  HGT1 bladder cancer at initial diagnosis and after a complete TUR
  Exclusion Criteria:
  -  abscence of muscularis propria in the TUR specimen

Relevance to patient case: not relevant
Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: A Dose Finding Study To Evaluate Safety, Drug Interaction, Tumor Markers Of Axitinib In Combination With MK-3475 In Adult Patients With Previously Untreated Advanced Renal Cell Cancer

Summary: Despite substantial improvements of patients outcome in advanced RCC, durable and complete response is uncommon. The majority of patients eventually develop resistance and exhibit disease progression. Combining a PD-1 inhibitor, which has shown single-agent efficacy with axitinib may provide additional clinical benefit compared to axitinib alone.


Eligibility: Inclusion Criteria:
  -  Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype with primary tumor resected
  -  At least one measureable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
  -  Eastern Cooperative Oncology Group performance status 0 or 1
  -  Controlled hypertension
  Exclusion Criteria:
  -  Prior treatment with systemic therapy for advanced RCC
  -  Prior adjuvant or neoadjuvant therapy if disease progression or relapse has occurred during or within 12 months after the last dose of treatment
  -  Prior treatment with any agent specifically targeting T-cell co-stimulation or checkpoint pathways
  -  Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis
  -  Diagnosis of any non-RCC malignancy occurring within 2 years prior to the date of randomization except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix or low grade prostate cancer with no plans for treatment intervention
  -  In past 12 months: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
  -  In past 6 months: deep vein thrombosis or pulmonary embolism

Relevance to patient case: not relevant
Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: Is the Nerve Growth Factor (NGF) a Useful Biomarker in Neurogenic Bladder Dysfunction After Spinal Cord Injury?

Summary: Spinal cord injury (SCI) almost always affects bladder function as well. As a result of this bladder dysfunction, individuals with SCI have to undergo regular invasive examination of their bladder function (urodynamic examination).
  The nerve growth factor (NGF) is released from smooth muscle cells of the bladder, and there are reports, that the concentration of NGF is elevated in the urine of patients with bladder dysfunction. The NGF concentration can also be measured in the blood. The concentration of NGF in the blood and urine of SCI individuals has not yet been investigated. These concentrations may correlate with the severity of bladder dysfunction, and may thus be used to replace or at least reduce the number of the more invasive urodynamic examinations.
  The hypothesis that urine and blood NGF concentrations in individuals with SCI are higher compared to individuals with healthy bladder function will be tested.


Eligibility: Control Group
  Inclusion Criteria:
  -  physiologic bladder function
  Exclusion Criteria:
  -  no signed consent form
  -  age <18 / >80 years
  -  urinary tract infection
  -  bladder surgery
  -  radiation therapy of the pelvic area
  -  pregnancy
  -  bleeding disorder
  Study Group
  Inclusion Criteria:
  -  neurogenic detrusor overactivity
  -  presentation for urodynamic examination
  Exclusion Criteria:
  -  no signed consent form
  -  age <18 / >80 years
  -  urinary tract infection
  -  bladder augmentation
  -  bladder evacuation by permanent catheterization
  -  radiation therapy of the pelvic area
  -  pregnancy
  -  bleeding disorder

Relevance to patient case: not relevant
Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: A Phase II, Single Arm Study of BGJ398 in Patients With Advanced Cholangiocarcinoma

Summary: This is a multi-center, open label, single arm phase II study evaluating BGJ398 anti-tumor activity in advanced or metastatic cholangiocarcinoma patients with Fibroblast Growth Factor receptor (FGFR) genetic alterations.

Detailed description: Adult patients with histologically or cytologically confirmed advanced or metastatic cholangiocarcinoma with FGFR genetic alterations who have evidence of radiologic progression following a cisplatin-and gemcitabine-containing regimen for advanced disease or a gemcitabine-containing regimen for those who are considered intolerant to cisplatin will be enrolled. Approximately 55 adult patients over age 18, both male and female will be enrolled. Of these 55 patients, 40 patients will have cholangiocarcinoma with identified FGFR2 gene fusions and up to 15 patients may have other FGFR genetic alterations. All patients will receive oral BGJ398, once daily, on a three weeks on (21 days), one week off (7 days) schedule. One treatment cycle will consists of 28 days.

Eligibility: Inclusion criteria:
  - Adult patients with histologically or cytologically confirmed cholangiocarcinoma at the time of diagnosis.
  Patients with cancers of the gallbladder or ampulla of Vater are not eligible.
  - Patients must have received at least one prior regimen containing gemcitabine with or without cisplatin for advanced/ metastatic disease. Patient should have evidence of progressive disease following prior regimen, or if prior treatment discontinued due to toxicity must have continued evidence of measurable or evaluable disease.
  Exclusion criteria:
  -  Prior or current treatment with a MEK or selective FGFR inhibitor
  -  insufficient organ function
  -  Absolutely Neutrophil Count (ANC) < 1,000/mm3 [1.0 x 109/L]
  -  Platelets < 75,000/mm3 [75 x 109/L]
  -  Hemoglobin < 109.0 g/dL
  -  Total bilirubin > 1.5x ULN
  -  Aspartate aminotransferase/glutamic oxaloacetic transaminase/GOT (AST/SGOT) and Alanine aminotransferase/glutamic pyruvic transaminase/GPT (ALT/SGPT) > 2.5x ULN (AST and ALT) > 5x upper limit of normal (ULN) in the presence of liver metastases)
  -  Serum creatinine > 1.5x ULN and a calculated or measured creatinine clearance < 45 mL/min
  -  Inorganic phosphorus outside of normal limits
  -  Total and ionized serum calcium outside of normal limits
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: not relevant
Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: Phase 1 Study of E7090 in Subjects With Solid Tumor

Summary: This is a Phase 1 study of E7090 in subjects with advanced solid tumors. This study will be conducted in 2 parts:
  1. Part 1 will be the dose escalation portion of this study to determine the maximum tolerated dose in subjects with solid tumors, and
  2. Part 2 will comprise cohort expansions to further characterize the safety and tolerability of E7090 and to assess preliminary efficacy of E7090 in subjects with solid tumors characterized by genetic abnormalities in FGF/FGFR pathway.


Eligibility: Inclusion Criteria: Part 1and Part 2
  1. Provide written informed consent
  2. Male or female subjects age >= 20 years at the time of informed consent
  3. Subjects with a histological and/or cytological diagnosis of solid tumor
  4. Subjects who failed standard therapies, or for which no appropriate treatment is available.
  5. Subjects with Performance Status (PS) score of 0-1 established by Eastern Cooperative Oncology Group (ECOG)
  6. Subjects who are expected to survive for 3 months or longer after starting administration of the investigational drug.
  Inclusion Criteria: Part 2 only
  7. Subjects with tumor expressing genetic abnormality in FGF/FGFR (fibroblast growth factor/ fibroblast growth factor receptor)pathway.
  Exclusion criteria
  1. Patients with brain metastasis who have clinical symptoms or requiring treatment.
  2. Medical history of clinically significant cardiovascular impairment
  3. Concomitant systemic infection requiring medical treatment
  4. Effusion requiring drainage
  5. Known intolerance to the study drug (or any of excipients)
  6. Subjects whose toxicity of previous treatment has not recovered to Grade 1 or lower (except for alopecia).
  7. Inability to take oral medication, or malabsorption syndrome, or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of E7090.
  8. Psychiatric disorder (e.g., alcohol or drug dependency) judged to be ineligible for study entry by the investigator or subinvestigator
  9. Females who are pregnant or breastfeeding
  10. Any subjects who are judged by the principal investigator or the other investigators to be inappropriate as subjects in this clinical study.

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with bladder cancer; genetic feature: FGFR3 (S249C)

Clinical trial: BIBF1120 in Patients With Advanced FGFR3 Mutated,Overexpressed,or Wild Type Urothelial Carcinoma

Summary: BIBF1120 in patients with advanced FGFR3 mutated, FGFR3 overexpressed, or FGFR3 wild type urothelial carcinoma of urinary bladder, urethra, ureter, and renal pelvis and who have failed platinum-based chemotherapy.


Eligibility: Inclusion Criteria:
  -  KPS 60%
  -  Histological confirmation of urothelial carcinoma , with metastatic disease
  -  Measurable disease
  -  Previously treated with platinum-based chemotherapy administered
  Exclusion Criteria:
  -  Radiographic evidence of cavitary or necrotic tumours
  -  Active brain metastasis.Leptomeningeal metastasis
  -  Chemotherapy, radiotherapy, targeted therapy with monoclonal antibodies or small tyrosine kinase inhibitors
  -  Grade 1 treatment-related toxicity from previous chemotherapy, radiotherapy, or targeted therapy
  -  Prior treatment with BIBF 1120 or other VEGFR inhibitors
  -  Significant cardiovascular diseases:
  -  Pericardial effusion
  -  Significant bleeding or thrombosis
  -  Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
  -  Major injuries within the past 10 days with incomplete wound healing and/or planned surgery during the on-treatment study period

Relevance to patient case: possibly relevant