araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: Study of WNT974 in Combination With LGX818 and Cetuximab in Patients With BRAF-mutant Metastatic Colorectal Cancer (mCRC) and Wnt Pathway Mutations

Summary: The purpose of this study is to assess the safety and anti-tumor activity of the triple combination of WNT974, LGX818 and cetuximab in BRAFV600-mutant mCRC with RNF43 mutations or RSPO fusions.
  The design of this study is based upon the translational and pre-clinical data that suggest that Wnt pathway signals, increased due to RNF43 mutations or RSPO fusions, cooperate with the EGFR and BRAF signals to maintain the growth of BRAFV600 CRCs. Inhibition of these signals with the triple combination of WNT974, LGX818 and cetuximab may result in anti-tumor activity.


Eligibility: Inclusion Criteria:
  -  Male or female aged ≥ 18 years
  -  Histological or cytological confirmed metastatic colorectal cancer
  -  Written documentation of KRAS wild-type status and BRAFV600-mutation with RNF43 mutation and/or RSPO fusion
  -  Progression of disease after at least one prior standard of care regimen or intolerant to irinotecan based regimens
  -  Availability of a representative tumor specimen (primary or metastatic, archival or newly obtained)
  -  Measurable disease as per RECIST v1.1
  -  Eastern cooperative oncology group (ECOG) performance status ≤ 2
  Exclusion Criteria:
  -  Phase II only: Prior treatment with RAF inhibitors, Wnt pathway inhibitors, cetuximab, panitumumab, and/or other EGFR inhibitors
  -  Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed to enroll
  -  Current treatment with medications or consuming foods that are strong inhibitors or inducers of CYP3A4/5 or herbal medications and that cannot be discontinued at least one week prior to the start of treatment.
  -  Symptomatic or untreated leptomeningeal disease
  -  Acute or chronic pancreatitis
  -  Clinically significant cardiac disease
  -  Patients with any of the following laboratory values at Screening/baseline
  -  Absolute neutrophil count (ANC) <1,500/mm3
  -  Platelets < 100,000/mm3
  -  Hemoglobin < 9.0 g/dL
  -  Serum creatinine >1.5 x ULN or calculated or directly measured CrCl < 50% lower limit of normal
  -  Serum total bilirubin >1.5 x ULN
  -  AST/SGOT and/or ALT/SGPT > 2.5 x ULN, (> 5 x ULN if liver metastases present)
  -  Patients with impaired hepatic function as defined by Childs-Pugh class B or C
  -  Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral WNT974/LGX818
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: A Study For Patients With EGFRm (Epidermal Growth Factor Receptor Mutant) Lung Cancer

Summary: Phase 1 - open label, multi-center, non-randomized, safety, pharmacokinetic and pharmacodynamics dose escalation study of PF-06459988 as a single agent in patients with advance EGFRm NSCLC (del 19, L858R, +/- T790M). The resulting PF-06459988 dose selected from the phase 1 portion will undergo a series of sub-studies to fully characterize the impact of food, antacid and CYP3A4 inhibitors/inducers. The PK studies are in addition to the MTD expansion and will be completed prior to the initiation of Phase 2. Phase 2 is an open label, multi-center single-arm study of PF-06459988 for the assessment of antitumor activity in patients with advanced EGFRm (del 19 or L858R) NSCLC with T790M.


Eligibility: Inclusion Criteria:
  -  Evidence of histological or cytologically confirmed diagnosis of locally advanced or metastatic EGFRm (del19 or L858R) NSCLC that is resistant to standard therapy. Patients must have progressed on treatment with an EGFR TKI, and may have also received other line of therapy.
  -  Tissue available (formalin fixed paraffin embedded (FFPE) block or 10 unstained sections (5 micron)
  -  Patients must be willing to participate in additional PK studies as required (cohort dependent); patients will be informed of which PK studies are required prior to consenting for study participation
  -  Adequate Bone Marrow Function (Complete Blood Count laboratory test results)
  -  Adequate Liver Function (Laboratory test)
  Exclusion Criteria:
  -  Previously diagnosed brain metastases, unless the patient has completed their treatment and has recovered from the acute effects of radiation therapy or surgery prior to the study registration, have discontinued corticosteroid treatment for these metastases for at least 2 weeks and are neurologically stable
  -  Systemic anti-cancer therapy within 4 weeks of starting study treatment excluding EGFR TKIs. Patients on EGFR TKIs must discontinue the agent for a minimum of 5 days prior to starting study drug
  -  Hypertension that cannot be controlled by medication (150/100 mmHg despite optimal medical therapy).

Relevance to patient case: definitely relevant
Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: Personalized Sequence for Thoracic, Esophageal, and H&N Cancer

Summary: The next generation of personalized medical treatment according to the type of personal genetic information are evolving rapidly. The genome analysis needs systematic infra and database based on personal genetic information Therefore, a big data of genome-clinical information is important.

Detailed description: To determine the feasibility of the use of tumor's molecular profiling and targeted therapies in the treatment of advanced cancer and to determine the clinical outcome(PFS, duration of response and overall survival) of patients with advanced cancer, the investigators are going to take a fresh tissue of patients and process molecular profiling.

Eligibility: Inclusion Criteria:
  -  metastatic, histologically confirmed NSCLC, head & Neck Cancer, Esophageal cancer
  Exclusion Criteria:
  -

Relevance to patient case: possibly relevant
Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: NEoadjuvant Gefitinib fOllowed by Surgery and gefiTinib In unresectAble sTage III NSCLC With EGFR Mutations.

Summary: The purpose of this study is to studying neoadjuvant gefitinib followed by surgery, followed by adjuvant gefitinib to see how well it works in treating patients with unresectable stage III NSCLC harboring EGFR mutations.

Detailed description: Concurrent chemoradiotherapy is the recommended therapeutic approach for patients with unresectable stage III non-small cell lung cancer (NSCLC), although surgery offers the chance of cure. With combined-modality therapy with radiation therapy and chemotherapy, the prognosis of stage III NSCLC remains poor. Gefitinib has shown great efficacy in NSCLC patients with EGFR mutations. This study is to studying neoadjuvant gefitinib followed by surgery, followed by adjuvant gefitinib to see how well it works in treating patients with unresectable EGFR mutant stage III NSCLC.

Eligibility: Inclusion Criteria:
  -  Target population is unresectable stage III (III A-bulky N2, III B) NSCLC with EGFR activating mutation in exon 19 or 21
  -  Written informed consent provided
  -  Aged 18-75 years
  -  Able to comply with the required protocol and follow-up procedures
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  -  Had a life expectancy of 12 weeks or more
  -  Adequate hematological function, liver function and renal function
  -  Female participants should not be pregnant or breast-feeding
  Exclusion Criteria:
  -  Known severe hypersensitivity to gefitinib or any of the excipients of this product
  -  Inability to comply with protocol or study procedures
  -  Had had previous chemotherapy, radiotherapy, or agents directed at the HER axis (e.g. erlotinib, gefitinib, cetuximab, trastuzumab)
  -  Had a history another malignancy in the last 5 years with the exception of cured basal cell carcinoma of the skin, cured in situ carcinoma of the uterine cervix and cured epithelial carcinoma of the bladder
  -  Interstitial pneumonia
  -  Eye inflammation not fully controlled or conditions predisposing the subject to this
  -  Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease)
  -  Known human immunodeficiency virus (HIV) infection
  -  Pregnancy or breast-feeding women
  -  History of neurologic or psychiatric disorders
  -  Ingredients mixed with small cell lung cancer patients

Relevance to patient case: possibly relevant
Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: Study on Potential Biomarkers Associated With Clinical Phenotype of EGFR-TKIs in No-small Cell Lung Cancer in China

Summary: To understand 295 gene mutation mutation status (include EGFR, HER2, KRAS, BRAF, PIK3CA,ect) by deep sequencing in Chinese patients with pulmonary adenocarcinoma and their relationships with the patients' clinical features (including sex, age, smoking history and adenocarcinoma subtype), specify the predictive significance of the genes mutations for new targeted therapies in NSCLC patients, and better understand the molecular mechanism drug resistance to EGFR-TKIs.

Detailed description: This study is prospective to identify biomarkers to resistant to afatinib，gefitinib and erlotinib in non-small cell lung cancer patients. Mutations of whole exon of 295 gene are analysed by deep sequencing in Chinese patients with non-small cell lung cancer and their relationships with the patients' clinical features (including sex, age, smoking history and adenocarcinoma subtype), specify the predictive significance of the genes mutations for new targeted therapies in NSCLC patients, and better understand the molecular mechanism drug resistance to EGFR-TKIs.

Eligibility: Inclusion Criteria:
  -  Age>18 years,both male and female
  -  Histologically confirmed patients with pulmonary adenocarcinoma (Stage I-IV)
  -  ECOG 0-2
  -  Patients with enough paraffin tissue specimens or fresh tissue for detection
  -  Quality of the DNA extracted from the tissue samples ensures that the DNA can be used in DNA sequencing
  -  Subjects who provide detailed clinical and follow-up information
  Exclusion Criteria:
  -  Patients with other tumors
  -  Patients suffering from other serious diseases like infectious diseases (viral hepatitis, HIV,etc)
  -  Pregnant women shall be excluded

Relevance to patient case: possibly relevant
Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Participants With EGFR Mutation-Positive Metastatic NSCLC

Summary: The main purpose of this study is to evaluate the safety and efficacy of ramucirumab in combination with erlotinib as compared to placebo in combination with erlotinib in participants with stage IV non small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Del19 and L858R). Safety and tolerability of ramucirumab in combination with erlotinib will be assessed in the first portion (Part A) before proceeding to the second portion of this study (Part B).
  The purpose of Part C is to determine the efficacy and safety of ramucirumab in combination with gefitinib in previously untreated East Asian participants with EGFR mutation-positive metastatic NSCLC and of ramucirumab in combination with osimertinib in those participants whose disease progressed on ramucirumab and gefitinib and that have T790M - positive metastatic NSCLC.


Eligibility: Inclusion Criteria:
  -  Cytologically or histologically confirmed diagnosis of Stage IV NSCLC as defined by the American Joint Committee on Cancer Staging Criteria for Lung Cancer (AJCC 7th edition 2009).
  -  Eligible for first-line treatment with erlotinib based on documented evidence of tumor harboring an activating EGFR mutation [exon 19 deletion or exon 21 (L858R) substitution mutation].
  -  Mandatory provision of adequate archived stage IV NSCLC tissue samples or tissue samples other than stage IV NSCLC may be acceptable (optional for part C).
  -  At least one measurable lesion.
  -  Life expectancy of at least 3 months.
  Exclusion Criteria:
  -  Known T790M EGFR mutation (not applicable for Part C Period 2).
  -  Known leptomeningeal carcinomatosis, uncontrolled/unstable spinal cord compression, or brain metastases.
  -  Serious illness or medical condition.
  -  Ongoing treatment with CYP3A4 inducers or strong inhibitors.
  -  Ongoing therapy with nonsteroidal anti-inflammatory drugs for more than 2 months.
  -  History of gross hemoptysis.
  -  Significant bleeding disorders.
  -  Radiologically documented evidence of major blood vessel invasion or encasement by cancer.
  -  Radiographic evidence of intratumor cavitation.
  -  History of gastrointestinal perforation within last 6 months.
  -  History of bowel obstruction, inflammatory enteropathy or extensive intestinal resection.
  -  History of any arterial thrombotic event within 6 months prior to enrollment.
  -  The participant has any known significant ophthalmologic abnormalities of the surface of the eye.

Relevance to patient case: definitely relevant
Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: T790M Mutation on ctDNA in Patients With NSCLC After EGFR-TKI Failure

Summary: The purpose of this study is to compare the frequency and abundance of T790M mutation among the different Clinical modes of EGFR-TKI failure.

Detailed description: An observational, non-interventional, multi-central study of comparison of the frequency and abundance of T790M mutation using both amplification refractory mutation system (ARMS) and digital droplet PCR (ddPCR) methods among the different Clinical modes of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) failure

Eligibility: Inclusion Criteria:
  -  Histologically confirmed stage IIIB/IV NSCLC.
  -  Investigator confirmed progression according RECIST 1.1 during EGFR-TKI treatment within 28 days of the enrollment
  -  Activating mutation (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q) in the EGFR gene or have had at least partial response with EGFR TKI lasting ≥ 6 months
  -  Patient must be able to comply with the protocol
  Exclusion Criteria:
  -  Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 defined disease progression for more than 28 days while on previous EGFR-TKI treatment.
  -  Patient has been treated with any investigational agent for any indication within 4 weeks of study treatment.
  -  Histologically confirmed small cell lung cancer or other metastatic tumors
  -  Patient with no histologic or cytological diagnosis.

Relevance to patient case: definitely relevant
Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: Safety and Efficiency of γδ T Cell Against Non Small Lung Cancer ( Without EGFR Mutation)

Summary: In this study, effects of γδT cells on human non small lung cancer ( without EGFR mutation) in combination with tumor reducing surgery, for example cryosurgery going to be investigated.

Detailed description: Non small lung cancer will be removed using tumor reducing surgery such as cryosurgery. PBMC of the patient will be separated from peripheral blood. After making them potential cancer killer γδ T Cell and DC-CIK, they will be infused to the patients as immunotherapy.

Eligibility: Inclusion Criteria:
  1. Age:18-75
  2. Karnofsky performance status >50
  3. Diagnosis with non small lung tumors based on histology or the current accepted radiological measures.
  4. Classification tumor,nodes,metastasis-classification(TNM) stage: Ⅱ,Ⅲ,Ⅳ Will receive cryosurgery, gd Tcells/ DC-CIK.
  5. Life expectancy: Greater than 3 months
  6. Ability to understand the study protocol and a willingness to sign a written informed consent document
  Exclusion Criteria:
  1. Patients with other kinds of cancer
  2. History of coagulation disorders or anemia
  3. Patients with heart disease and diabetes

Relevance to patient case: not relevant
Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: Study for Treatment of Patients With EGFR Mutant, T790M-negative NSCLC

Summary: This phase 2 study is designed to evaluate the safety and activity of TH-4000 (Tarloxotinib), a hypoxia-activated prodrug, in patients with EGFR-Mutant, T790M-Negative, Advanced non-small cell lung cancer (NSCLC).

Detailed description: A single arm open label multi-center Phase 2 study in which the pharmacokinetics, safety, tolerability and efficacy of TH-4000 (Tarloxotinib) will be assessed in patients with EGFR mutant, T790M negative advanced NSCLC. Patients must have demonstrated progression during EGFR TKI therapy.
  Hypoxia PET scans will be obtained in select centers to analyze potential predictors of tumor response.

Eligibility: Key Eligibility Criteria:
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  -  Confirmed recurrent Stage IV NSCLC which progressed while on treatment with EGFR TKI
  -  Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
  -  Documented evidence of an EGFR mutation known to be associated with an EGFR TKI sensitivity
  -  No T790M mutation or small cell transformation including an assessment from tumor biopsy obtained while on or subsequent to the most recent EGFR TKI therapy
  -  Acceptable laboratory results as indicated by protocol
  -  Acceptable cardiac function as indicated by protocol
  Key Exclusion Criteria:
  -  Receiving medication that prolongs QT interval, with a risk of causing Torsades de Pointes (TdP) unless ECG meets inclusion criteria while on a stable dose of the medication
  -  Family history of long QTc syndrome
  -  Symptomatic central nervous system (CNS) lesions
  -  Radiation therapy within 2 weeks prior to the first dose of study medication
  -  Major surgery within 4 weeks or minor surgery within 2 weeks prior to the first dose of study medication
  -  Concurrent active malignancy requiring systemic treatment
  -  Any other serious uncontrolled medical disorders or psychological conditions that may interfere with study conduct including but not limited to: clinically significant active infection (e.g., tuberculosis, viral hepatitis, human immunodeficiency virus [HIV]), recent (within 6 months) myocardial infarction or unstable angina, congestive heart failure, poorly-controlled hypertension or diabetes, concurrent active malignancy, or psychiatric condition that may interfere with the patient's ability to follow study procedures
  -  Pregnant or breast-feeding

Relevance to patient case: definitely relevant
Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: A Safety and Efficacy Study of INC280 Alone, and in Combination With Erlotinib, Compared to Chemotherapy, in Advanced/Metastatic Non-small Cell Lung Cancer Patients With EGFR Mutation and cMET Amplification

Summary: The purpose of this study is to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of INC280 in combination with erlotinib in the Phase Ib of this study, and to assess the anti-tumor activity and safety of INC280 alone, and in combination with erlotinib, versus platinum with pemetrexed in the Phase II of this study, in adult patients with EGFR mutated, cMET amplified, advanced/metastatic non-small cell lung cancer with acquired resistance to prior EGFR TKI.

Detailed description: The decision was taken to halt study enrollment with Cohort #3 in Phase 1b. Therefore, activities for the planned Phase 2 were not initiated.
  This decision to stop further development of this combination was taken due to the challenge for enrollment in this very rare patient population along with the rapidly evolving disease landscape setting.

Eligibility: Inclusion Criteria:
  -  Locally advanced or metastatic NSCLC
  -  EGFR mutation (L858R and /or ex19del)
  -  cMET amplification by FISH (GCN ≥ 6),
  -  Acquired resistance to EGFR TKI (1st or 2nd génération)
  -  ECOG performance status (PS) ≤ 1.
  Exclusion Criteria:
  -  Prior treatment with 3rd generation TKI
  -  PhaseII : Prior treatment with any of the following agents:
  -  Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor.
  -  Concomitant EGFR TKI and platinum based chemotherapy as first line regimen.
  -  Platinum-based chemotherapy as first line treatment

Relevance to patient case: possibly relevant
Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: Afatinib Genomic Landscape

Summary: The investigators propose to conduct a pilot feasibility study of single agent afatinib in patients with previously untreated metastatic EGFR (epidermal growth factor receptor) mutant adenocarcinoma of the lung (NSCLC = non-small cell lung cancer) with the sole purpose of characterizing the genomic landscape before afatinib and at the time of disease progression.

Detailed description: The current proposal will include exome and transcriptome sequencing from blood collected at baseline along with tumor samples obtained prior to starting afatinib and at the time of disease progression (a total of two tissue samples and one blood sample per patient). The samples will be collected via consent to the IRB (Institutional Review Board) approved banking study "Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or Mesothelioma".
  If carried out successfully, the proposed strategy very likely will lead to a larger and adequately powered study (perhaps using whole genome sequencing) to understand fully evolving molecular changes due to clonal selection under treatment pressure. The pace of progress in the field of sequencing technology currently underway is only likely to accelerate in the near future yielding richer and highly content-rich information. Moreover, it is likely that genomic information from DNA sequencing and transcriptome will be supplemented by analyses of translatomes and proteomes.
  Successful completion of the proposed study would enable future studies to fully harness the potential of emerging technologies to develop novel approaches to treat and even ideally prevent resistance to EGFR TKIs (tyrosine-kinase inhibitor) and other molecularly targeted therapies. This could serve as a template for other cancer types as well. Over time, this approach, broadly used, would create simultaneously, highly valuable annotated tumor specimens along with germ line DNA for high-throughput genomic studies to identify novel targets and their impact on the course of disease. Re-analyzing molecular changes in the tumor at the time of disease progression would likely be a new standard of care to guide salvage therapy.

Eligibility: Inclusion Criteria/Exclusion Criteria:
  -  Diagnosis of metastatic stage IIIB/IV lung adenocarcinoma
  -  Presence of known sensitizing mutations in EGFR TK domain (exon 19 deletion and L858R)
  -  Absence of known resistant mutations in the EGFR TK domain (T790M)
  -  Consented to HRPO # 201305031 ("Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or Mesothelioma")
  -  No prior treatment for this malignancy
  -  No prior localized therapy to the biopsy site
  -  Planned treatment with standard of care afatinib at 40 mg QD (daily)
  -  Not pregnant or breastfeeding
  -  At least 18 years of age

Relevance to patient case: definitely relevant