araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Study of Split-course Chemoradiotherapy For Postoperative Locoregional Recurrence Of Non-small Cell Lung Cancer

Summary: This Phase II randomized study is to determine the efficacy of split-course irradiation with concurrent chemotherapy in locoregional recurrence of non-small cell lung cancer after surgical resection

Detailed description: This Phase II randomized study is to determine the efficacy of split-course irradiation with concurrent chemotherapy in locoregional recurrence of non-small cell lung cancer after surgical resection.
  Patients received four cycles of weekly docetaxel(25mg/㎡) and nedaplatin(25mg/㎡), each of 1 day's duration, combined with split-course thoracic radiotherapy of 40-51 Gy/10-17 fractions and 15-24 Gy/5-8 fractions administered in the first and second courses, respectively, with one-month break. The primary end point is progression-free survival, which is the time that passes from the first day of radiotherapy to the date at which disease progresses. Progression-free survival will be calculated using the Kaplan-Meier method.Toxicities will be graded according to CTCAE v. 4.0.

Eligibility: Inclusion Criteria:
  -  Pathologic confirmation of NSCLC.
  -  Patients have measurable or evaluable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  -  Postoperative locoregional recurrence including ipsilateral hemithorax and the mediastinum.
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  -  Previously treated with chemotherapy or treatment-naive
  -  No previous chest radiotherapy, immunotherapy or biotherapy
  -  Hemoglobin≥10 mg/dL, platelet≥100000/μL,absolute neutrophil count ≥1500/μL
  -  Serum creatinine ≤1.25 times the upper normal limit(UNL), or creatinine clearance≥60 ml/min
  -  Bilirubin ≤1.5 times UNL, AST（SGOT）≤2.5 times UNL ,ALT（SGPT）≤2.5 times UNL,alkaline phosphatase ≤5 times UNL
  -  Forced expiratory volume at one second (FEV1) >0.8 L
  -  Coagulation tests within normal limits
  -  patients and their family signed the informed consents
  Exclusion Criteria:
  -  Previous or recent another malignancy, except nonmelanoma skin cancer or cervical cancer in situ
  -  Second primary carcinoma of the lung
  -  Contraindication for chemotherapy
  -  Malignant pleural or pericardial effusion.
  -  Women in pregnancy, lactation period, or no pregnancy test 14 days before the first dos
  -  Women who has the probability of pregnancy without contraception
  -  Tendency of hemorrhage
  -  In other clinical trials within 30 days
  -  Addicted in drugs or alcohol, AIDS patients
  -  Uncontrollable seizure or psychotic patients without self-control ability
  -  Severe allergy or idiosyncrasy
  -  Not suitable for this study judged by researchers

Relevance to patient case: not relevant
Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Early Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy

Summary: A comparison of baseline tumor characteristics in oncogene-driven cancers to tumor characteristics after early response to Tyrosine Kinase Inhibitor (TKI) targeted treatment will allow identification of early adaptive mechanisms of cell survival. This will facilitate targeting and termination of these survival/ resistance pathways before they develop with rational combinations of therapeutic agents to improve outcomes.


Eligibility: Inclusion Criteria:
  -  Carry a diagnosis of stage IV lung adenocarcinoma with an activating mutation determined to respond to an estimated glomerular filtration rate (EGFR) TKI, alkaline phosphatase (ALK) or ROS Proto-Oncogene 1 (ROS1) fusion or BRAF V600E.
  -  Aged 18 - 85 years or older
  -  ECOG 0-2
  -  Have a histologically confirmed diagnosis of lung adenocarcinoma harboring an EGFR sensitizing mutation (including, but not limited to: G719X, del exon 19, or L858R).
  -  No prior therapy for metastatic disease.
  -  Planned treatment with a single agent EGFR TKI including but not limited to:
  1. erlotinib,
  2. gefitinib,
  3. rociletinib (CO-1686),
  4. afatinib, or
  5. osimertinib (AZD-9291).
  -  Patients must have at least one site of measurable disease ≥ least 2cm.
  -  Primary disease site or site of metastatic disease must be amenable to biopsy.
  -  Patients must have the ability to understand and willingness to sign an informed consent document.
  -  Patients must be willing to undergo an initial pre-treatment biopsy of tumor tissue (or have previously collected frozen tissue) and a follow-up biopsy 2 weeks (+/- 1 week) after treatment start
  Exclusion Criteria:
  -  Concurrent health problem which would preclude tissue biopsy (eg hemophilia or other bleeding predisposition).
  -  Patients whose only source of biopsiable disease is:
  1. intracranial,
  2. pleural effusion or any lesion that is deemed unsafe to biopsy by the treating physician or,
  3. interventional radiology.

Relevance to patient case: possibly relevant
Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy of NSCLC Patients in China

Summary: To evaluate the concordance of sensitizing mutations detected between paired plasma and tissue samples; the correlation between the clonal status of sensitizing mutations and targeted therapy response; and the prognostic impact of the relative abundance of sensitizing / resistance mutations.

Detailed description: In the study, 500 advanced NSCLC patients will be recruited. All the patients will receive biopsy genotype assay and circultating tumor DNA (ctDNA) liquid biopsy. Patients who carry actionable EGFR mutation, ROS1 fusion, ALK fusion or MET exon 14 skipping mutation will receive TKI treatment according to guidelines. During the TKI treatment, every patients will take liquid biopsy assay to monitor the mutation status. The study will be ended when all the patients had a progressive disease (PD) in their targeted lesion.

Eligibility: Inclusion Criteria:
  -  Provision of informed consent
  -  Newly diagnosed and histological or cytological confirmed stage IIIB-IV lung adenocarcinoma or non-smoking squamous cell carcinoma patients according to the AJCC staging system. The stage IV lung cancer and brain metastasis can be diagnosed by imaging and enhanced CT respectively
  -  ECOG performance status 0-2 with expected more than 6 months of survival time
  -  Willingness to comply with required protocols and give permission to use the data for clinical research and products development
  Exclusion Criteria:
  -  Patients have other primary cancers
  -  Patients have symptomatic brain metastasis, complications that are associated with brain metastasis or cognitive disorders
  -  Patients failed in either plasma or tissue sample QC

Relevance to patient case: not relevant
Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Expanded Access to Entrectinib for Cancers With NTRK1/2/3, ROS1, or ALK Gene Fusions

Summary: Expanded access to entrectinib will be given to patients with cancers harboring NTRK1/2/3, ROS1, or ALK gene fusions who do not qualify for participation in, or who are otherwise unable to access, an ongoing clinical trial for entrectinib.


Eligibility: Inclusion Criteria:
  -  Diagnosis of advanced cancer with an NTRK1, NTRK2, NTRK3, ROS1, or ALK gene fusion
  -  Unable to participate in an ongoing entrectinib (RXDX-101) clinical trial
  -  Willing and able to provide written, signed informed consent
  -  Medically suitable for treatment with entrectinib (RXDX-101)
  Exclusion Criteria:
  -  Currently enrolled in an ongoing clinical study with any other investigational agent

Relevance to patient case: possibly relevant
Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Frequency of EGFR and KRAS Mutations and Clinical-prognostic Correlation in Brazilian Lung Cancer Patients

Summary: The assessment of the type and frequency of EGFR and KRAS mutations in lung cancer patients, as well as clinical-prognostic correlation, are crucial in the era of targeted therapies. EGFR-activating mutations predict responsiveness to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients and KRAS analysis will be useful in a near future for newest target drugs. In Brazil, few data about the prevalence of EGFR and KRAS mutations is available and their knowledge would allow optimize personalized medicine.

Detailed description: Assessment of the types and frequency of EGFR and KRAS mutations in NSCLC, as well clinical-prognostic correlations has been extensively studied in many populations. Few Brazilian studies evaluating mutational status in NSCLC has been done so far, none of then explored the regional background nor have considered the quantitative analysis of mutant cell in each sample. Quantitative analysis of the tumor maybe relevant for treatment design for positive samples, p.e a tumor with 90% of mutant clones versus a 15% of mutant clones, which can be obtained currently by the method of pyrosequencing. In this study, investigators will assess EGFR and KRAS status through the pyrosequencing quantitative technique, and will also correlate these with clinical-pathological variables among both adenocarcinoma and squamous cell histological subtypes. So far, no study that have made this correlation is available.

Eligibility: Inclusion Criteria:
  -  Brazilian patients with metastatic non-small cell lung cancer.
  Exclusion Criteria:
  -  Small cell lung cancer and non-metastatic patients.

Relevance to patient case: not relevant
Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Expanded Access For Lorlatinib For Patients With Non Small Cell Lung Cancer ALK Positive or ROS1 Positive

Summary: This expanded access study has being designed following a demand from the FDA, given the increase in the number of request for single patient INDs for lorlatinib

Detailed description: Given that an Expanded Access study does not meet the definition of a controlled clinical investigation, and as such, is not considered an applicable drug clinical trial per NIH, Basic Results for such studies are not required to be reported. Protocol B7461020 has been identified as an Expanded Access trial, and has been registered to ClinicalTrials.gov, however Basic Results will not be posted. This statement has been placed in the Detailed Description section of the protocol registration on ClinicalTrials.gov.

Eligibility: Inclusion Criteria:
  -  Ineligibility for participation in any ongoing clinical study of the investigational product
  -  Age ≥18 years
  -  Histologically or cytologically diagnosis of metastatic NSCLC that carries an ALK rearrangement or a ROS1 rearrangement
  -  For ALK positive patients: failure to prior treatment with at least one ALK-TKI. If prior ALK-TKI was crizotinib, additional prior treatment required with at least one second generation ALK-TKI registered and commercially available. For patients with resistance mutations not covered by other inhibitors (eg, ALK G1202R resistance mutation), prior treatment with an ALK/ROS1 inhibitor is not required.
  -  For ROS1 positive patients: failure to prior treatment with at least crizotinib
  -  Adequate bone marrow, liver, renal, pancreatic functions
  -  Negative pregnancy test at screening
  Exclusion Criteria:
  -  Previous surgery, chemotherapy, radiotherapy or other anti cancer therapy or participation in other studies with investigational drugs within the timeframe indicated in the protocol
  -  History of interstitial fibrosis or interstitial lung disease
  -  Concomitant use of prohibited medication
  -  Clinically significant cardiovascular disease: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, second degree or third degree atrioventricular block (unless paced) or any AV block with PR >220 msec
  -  Ongoing cardiac dysrhythmias, uncontrolled atrial fibrillation,bradycardia, ECG with QTc >470 msec, or congenital long QT syndrome
  -  History of or predisposing characteristics for acute pancreatitis

Relevance to patient case: possibly relevant
Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Phase 1/2 Study of LOXO-195 in Patients With Previously Treated NTRK Fusion Cancers

Summary: This is a Phase 1/2, multi-center, open-label study designed to evaluate the safety and efficacy of LOXO-195 when administered orally to patients age ≥ 1 month and older with NTRK fusion cancers treated with a prior TRK inhibitor.

Detailed description: The trial will be conducted in 2 parts: dose escalation (Phase I ) and dose expansion (Phase 2) . Patients with unresectable or metastatic solid tumors are eligible if progressed or intolerant to prior TRK inhibitor. During Phase 1, a maximum tolerated dose (MTD)/recommended dose for further study will be identified for in patients age 12 and older and patients age <12. During Phase 2, the same patient population as designated for Phase 1 will be treated with the dose of LOXO-195 which has been identified during phase 1 to assess specified endpoints.

Eligibility: Key Inclusion Criteria:
  -  Advanced solid tumor for which, in the opinion of the Investigator, no other standard therapy offers greater benefit.
  -  A solid tumor diagnosis in the setting of:
  1. a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor
  2. a documented NTRK fusion unresponsive to a prior TRK inhibitor
  3. a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor
  -  NTRK gene fusions will be identified via a CLIA certified (or equivalent) laboratory. Exception: Patients with Infantile Fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) may be enrolled based on ETV6+ FISH test without identifying NTRK3
  -  Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3 (age ≥16) or Lansky Performance Score (LPS) ≥40% (age<16). If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Status (KPS) (age ≥16) or LPS (age<16) ≥ 50%
  -  Life expectancy > 4 weeks
  -  Adequate hematologic, hepatic and renal function.
  -  Patients with stable CNS primary tumor, brain metastases, or treated spinal cord compression are eligible if neurological symptoms and steroid use (if applicable) have been stable for 7 days prior to the first dose of LOXO-195
  -  Ability to receive study drug orally or by enteral administration
  Key Exclusion Criteria:
  -  Required treatment with certain strong CYP3A4 inhibitors or inducers.
  -  Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of LOXO-195 or prolongation of the QT interval corrected (QTcF) > 480 msec within the past 6 months
  -  Major surgery within 7 days of enrollment
  -  Uncontrolled systemic bacterial, fungal or viral infection
  -  Pregnancy or lactation.
  -  Known hypersensitivity to any of the components of LOXO-195 or Ora-Sweet® SF and OraOlus, for patients receiving liquid suspension

Relevance to patient case: not relevant
Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Efficacy and Safety of Osimertinib for HK Chinese With Metastatic T790M Mutated NSCLC-real World Setting.

Summary: To assess the efficacy of single-agent osimertinib in relation to EGFR T790M mutant allele fraction (AF) in a real-world setting.

Detailed description: This study will assess the efficacy and safety of single-agent osimertinib in patients with locally advanced or metastatic EGFR T790M-positive NSCLC within the context of the early access program in Hong Kong. In particular, osimertinib treatment efficacy will be assessed in the context of the relationship between EGFR T790M mutant AF and survival outcomes, particularly overall survival. In a real-world setting, analysis of overall survival benefit is considered less sensitive to differences in healthcare systems and standards. Other clinical outcomes including response rate (based on physician's judgement) and time to treatment discontinuation (TTD) will be examined. This study will also describe current practice for molecular testing and EGFR mutation profiles in this patient population.

Eligibility: Inclusion Criteria:
  -  Patients enrolled in AZD9291 Named Patient Program in Hong Kong
  -  Patients with confirmed advanced (locally advanced (stage IIIB) or metastatic (stage IV)) NSCLC with a positive test result for the EGFR T790M mutation
  -  Patients who have previously received EGFR TKI therapy or discontinued an EGFR TKI at the time of enrolment in the study
  -  Provision of written informed consent (for patients alive at the time of study enrolment)
  -  Documented patients with trackable medical records
  Exclusion Criteria:
  -  Enrolment in studies that prohibit any participation in this non-interventional study

Relevance to patient case: not relevant
Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Detection of Either the EML4-ALK Gene Rearrangements or the T790M EGFR Mutation in the Plasma of Advanced NSCLC Patients

Summary: Demonstrate feasibility of detection of EML4-ALK fusion transcripts and T790M EGFR mutation from exosomes in the circulation of Non-Small Cell Lung Cancer (NSCLS) patients.

Detailed description: The goal of this study is two-fold: 1) Demonstrate feasibility of detection of EML4-ALK fusion transcripts in the circulation of NSCLC patients positive for ALK on tissue analysis, using an institutionally accepted assay; 2) Demonstrate feasibility of detection of T790M EGFR mutation in the circulation of NSCLC patients positive for T790M on tissue analysis, using an institutionally accepted assay.

Eligibility: Inclusion Criteria:
  1. Participants must have histologically confirmed NSCLC, stage IIIB- IV, and have tested positive for the presence of EML4-ALK on tissue specimen, fresh or archived, using an institutionally accepted assay.
  2. Age of 18 years or older.
  3. Participants are being considered for ALK-directed therapy or have progressed on EGFR TKI treatment.
  4. Participants must have hemoglobin > 10 mg/dL.
  5. Ability to understand and willingness to sign a written informed consent document.
  Exclusion Criteria:
  1. Hepatitis (all types) in patient's medical record
  2. HIV documented in patient's medical record
  3. Hemoglobin < 10 mg/dL
  4. Less than 18 years of age
  5. Histologically confirmed NSCLC Stage I-IIIA
  6. Tested negative for the presence of EML4-ALK and T790M EGFR on tissue

Relevance to patient case: not relevant
Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Efficacy and Safety of Targeted Precision Therapy in Refractory Tumor With Druggable Molecular Event

Summary: This study is intended to evaluate efficacy and safety of targeted precision therapy in patients with refractory tumor, including rare tumor without standard recommended treatment and common tumor after multiple line of therapy.

Detailed description: The individuals recruited in the present study are with solid tumor, mainly including two parts: first, rare tumor without standard recommended treatment such as atypical fibrous histiocytoma; second, common tumor after multiple line of therapy such as lung cancer, gastric cancer, colorectal cancer, etc. All patients have no any standard therapy based on NCCN guideline when recruiting. Next-generation sequence was used to detect druggable molecular event including gene mutation, gene fusion, amplification, etc. Then patients with molecular events were treated with corresponding targeted drug and followed-up, and not limited tumor type. The efficacy and safety of targeted drug were evaluated.

Eligibility: Inclusion Criteria:
  -  Malignant solid tumors diagnosed histologically;
  -  Common solid tumor patients have no any standard choice after multiple line of therapy; Rare solid tumor did not have any standard recommended treatment;
  -  Expected survival ≥ 1 month;
  -  ECOG / PS score: 0-2, and the main organ function to meet the following criteria: HB ≥ 90g / L, ANC ≥ 1.5 × 109 / L, PLT ≥ 80 × 109 / L,BIL <1.5 times the upper limit of normal (ULN); Liver ALT and AST <2.5 × ULN and if liver metastases, ALT and AST <5 × ULN; Serum Cr ≤ 1 × ULN, endogenous creatinine clearance ≥50ml/min
  Exclusion Criteria:
  -  Patient still has standard treatment therapy based on NCCN guidance;
  -  Patient can not comply with research program requirements or follow-up;

Relevance to patient case: not relevant
Patient case: 72-year-old male with lung adenocarcinoma; genetic feature: EZR-ROS1 fusion

Clinical trial: Study of Oral cMET Inhibitor INC280 in Chinese Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (NSCLC)

Summary: A phase II study to evaluate antitumor activity of oral cMET inhibitor INC280 in adult Chinese patients with EGFR wild-type, advanced non-small cell lung cancer (NSCLC) who have received one or two prior lines of systemic therapy for advanced/metastatic disease as measured by overall response rate (ORR). The study will also evaluate safety and pharmacokinetics of INC280.


Eligibility: Inclusion Criteria:
  -  Stage IIIB or IV NSCLC (any histology) at the time of study entry
  -  Histologically or cytologically confirmed diagnosis of NSCLC that is:
  1. EGFR wt as per patient standard of care by a validated test
  2. AND ALK-negative rearrangement as part of the patient standard of care by a validated test
  3. AND (by central assessment) either:
  -  Cohort 1: Pre-treated patients with cMET GCN ≥ 6 or
  -  Cohort 2: Pre-treated patients with cMET GCN ≥4 and < 6, or
  -  Cohort 3: Pre-treated patients with cMET mutations regardless of cMET GCN, or
  -  Patients must have failed one or two prior lines of systemic therapy for advanced/metastatic disease
  -  At least one measurable lesion as defined by RECIST 1.1
  -  Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter the study.
  -  Patients must have adequate organ function
  -  ECOG performance status (PS) of 0 or 1
  Details and other protocol-defined inclusion criteria may apply
  Exclusion Criteria:
  -  Prior treatment with crizotinib, or any other cMET or HGF inhibitor
  -  Patients with characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations
  -  Patients with characterized ALK-positive rearrangement
  -  Clinically significant, uncontrolled heart diseases.
  -  Patients receiving treatment with medications that cannot be discontinued at least 1 week prior to first INC280 treatment and for the duration of the study:
  -  Strong and moderate inhibitors of CYP3A4
  -  Strong inducers of CYP3A4
  -  Impairment of GI function or GI disease that may significantly alter the absorption of INC280
  -  Patients receiving treatment with any enzyme-inducing anticonvulsant
  -  Previous anti-cancer and investigational agents within 4 weeks or ≤ 5 x half-life of the agent (whichever is longer) before first dose
  -  Pregnant or nursing women
  -  Women of child-bearing potential, unless they are using highly effective methods of contraception
  -  Sexually active males unless they use a condom during intercourse
  Other protocol-defined exclusion criteria may apply

Relevance to patient case: not relevant