araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 54-year-old female with non-small cell lung cancer; genetic feature: EGFR (D770N)

Clinical trial: An Explorative Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation

Summary: Objective(s):To investigate the efficacy and safety of afatinib in EGFR, HER 2 and HER3 mutated cancers, regardless of cancer type, excluding EGFR mutated non-small cell lung cancer.
  Methodology:Open label, genomic driven trial (basket trial)
  No. of patients total entered:Optimal Simon two stage design for the three genetic driven cohorts: 10 patients will be enrolled per cancer type in the first stage and an additional 19 in the second stage (maximum total 87 patients)
  Indication : cancers harbouring an EGFR mutation(excluding non-squamous non- small cell lung cancer, a registered indication), a HER2 mutation or a HER3 mutation
  Test product(s) : Afatinib At progression paclitaxel will be added for those patients that have no contra-indications
  dose: Starting dose of afatinib at 40 mg/day. Dose increase to 50 mg in the absence of adverse events. Stepwise dose reduction to 30,20, 10 mg/day according to drug-related adverse events.
  At progression, addition of paclitaxel 80 mg/m2 weekly 3w/4 to afatinib 40 mg/day .
  mode of admin. : Oral for afatinib Intravenous for paclitaxel
  Duration of treatment: Continuous treatment until progression or unacceptable adverse events or withdrawal of consent.
  At disease progression, add paclitaxel until progression or unacceptable adverse event or withdrawal of consent if no contra-indications.
  Criteria for efficacy: Primary Endpoint:
  • Response rate (CR+ PR) via RECIST v1.1
  Secondary Endpoints:
  -  Disease control rate (CR+PR+SD)
  -  Progression free survival
  -  Overall survival
  -  To correlate tumor response with findings on tumor biopsies
  -  To investigate resistance mechanisms
  -  response rate (CR+ PR) determined by RECIST and progression free survival on the combination therapy of afatinib and paclitaxel
  Criteria for safety: Incidence and intensity of adverse events according CTCAE v4.0


Eligibility: Inclusion Criteria:
  -  Women and men with locally advanced or metastatic cancers harboring either an activating EGFR mutation or a HER2 mutation or a HER3 mutation
  -  Failure of at least one line of standard systemic therapy
  -  No eligibility for other open genomic driven phase I, II or III trial available for these tumor genotypes
  -  ECOG performance status ≤2
  -  Patient with a life expectancy >3 months
  -  Patients able to provide written informed consent prior to enrollment into the clinical trial.
  -  Adequate organ function
  Exclusion Criteria:
  -  Non squamous non-small cell lung cancer harbouring an EGFR mutation (registered indication)
  -  Chemotherapy, biological therapy or investigational agents within four weeks prior to the start of study treatment
  -  Known hypersensitivity to afatinib or the excipients of any of the trial drugs
  -  Prior treatment with afatinib

Relevance to patient case: not relevant
Patient case: 54-year-old female with non-small cell lung cancer; genetic feature: EGFR (D770N)

Clinical trial: Pharmacokinetic Boosting of Osimertinib

Summary: The main objective of this study is to evaluate if systemic exposure of osimertinib (i.e. AUC) is increased when osimertinib is co-administered with cobicistat in patients with relatively low plasma trough concentration while receiving the standard osimertinib dose.

Detailed description: Osimertinib is a new targeted agent registered for the treatment of patients with EGFR-mutated NSCLC. However, the costs of those new treatments are extremely high. Osimertinib is mainly metabolized by CYP3A4, and partially by CYP3A5. Combination of osimertinib with a strong CYP3A4-inhibitor may result in a smaller first-pass effect and a decreased clearance of osimertinib, thereby increasing the exposure to osimertinib.
  Cobicistat is a strong CYP3A4-inhibitor, this mechanism may be used to boost osimertinib, as is done for other drugs, mainly drugs used to treat HIV-infected patients.
  Using this personalized treatment approach and combining the concepts of therapeutic drug monitoring (TDM) and pharmacokinetic boosting, osimertinib therapy could become much more cost-effective. By reducing the necessary dose of osimertinib, this strategy may ultimately result in a significant reduction in drug costs, as the additional expenditure for the CYP3A4 inhibitor and blood sample analysis are negligible compared to the price of osimertinib.

Eligibility: Inclusion Criteria:
  -  Patients with EGFR-mutated NSCLC receiving standard treatment with osimertinib for at least two months, without any signs of disease progression.
  -  Stable disease, partial or complete response on the most-recent tumour-response evaluation.
  -  Age ≥ 18 years
  -  WHO performance status ≤ 2.
  -  Able and willing to give written informed consent.
  -  Able and willing to undergo blood sampling for pharmacokinetic analysis.
  -  Patients with osimertinib plasma trough concentration below 135 ng/mL. Plasma trough concentration of osimertinib will be determined in another study (METC MUMC: 2018-0800).
  Exclusion Criteria:
  -  Any concurrent medication that is known to strongly inhibit or induce CYP3A4.
  -  Any concurrent medication that is primarily metabolized by CYP3A4 with a narrow therapeutic window.
  -  Impairment of gastrointestinal function that may alter the absorption of osimertinib or cobicistat (e.g. ulcerative disease, uncontrolled nausea or vomiting, malabsorption syndrome, small bowel resection).
  -  Refusing to refrain from consuming CYP3A4 influencing products, e.g. grapefruit(juice), St. John's wort.
  -  Pregnancy or breast feeding
  -  Child-Pugh score class C, chronic liver disease.

Relevance to patient case: possibly relevant
Patient case: 54-year-old female with non-small cell lung cancer; genetic feature: EGFR (D770N)

Clinical trial: A Study of BPI-7711 Capsule in Non-small Cell Lung Cancer Patients

Summary: A randomized, double-blind, positive controlled phase III study to evaluate the efficacy and safety of BPI-7711 capsule in locally advanced or recurrent/metastatic treatment-naïve non-small cell lung cancer patients with EGFR mutation

Detailed description: This is a Phase III clinical study, which aims to compare the efficacy and safety of BPI-7711 capsule and gefitinib tablet in the treatment of initially-treated patients with locally advanced or recurrent metastatic with EGFR mutation.

Eligibility: Inclusion Criteria:
  -  Histologically or cytologically confirmed non-small cell lung cancer.
  -  The ECOG score of performance status is 0-1.
  -  Locally advanced or recurrent metastatic NSCLC that has never received systemic treatment.
  -  According to RECIST1.1 criteria, there is at least 1 measurable lesion that has not been previously irradiated.
  -  Prior to enrollment, a central laboratory testing report has confirmed that the tumor has one of two common EGFR mutations positive that are sensitive to EGFR-TKI therapy, accompanied with or not accompanied with other EGFR mutation, with the exception of exon 20 insertion.
  Exclusion Criteria:
  -  Previously received systemic treatment for locally advanced or recurrent metastatic cancer.
  -  Primary T790M mutation-positive patient.
  -  Previous interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring hormonal therapy, or any clinically proven active interstitial lung disease.
  -  Known active infections such as hepatitis B, hepatitis C, and human immunodeficiency virus.
  -  Local radiation therapy is carried out within 1 week; more than 30% bone marrow radiation therapy or extensive radiation therapy is performed within 4 weeks.
  -  ≤ 4 weeks from major surgery or ≤ 2 weeks from minor surgery.

Relevance to patient case: possibly relevant
Patient case: 54-year-old female with non-small cell lung cancer; genetic feature: EGFR (D770N)

Clinical trial: Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous NSCLC

Summary: This study will compare the efficacy of the investigational agent sitravatinib in combination with nivolumab versus docetaxel in patients with advanced non-squamous NSCLC who have previously experienced disease progression on or after platinum-based chemotherapy in combination with checkpoint inhibitor therapy.

Detailed description: Sitravatinib is a spectrum-selective receptor tyrosine kinase (RTK) inhibitor that inhibits several closely related RTKs, including the TAM family (TYRO3, AXL and MERTK), VEGFR2, KIT and MET. Nivolumab is a human IgG monoclonal antibody that binds to the PD-1 receptor and selectively blocks the interaction with its ligands PD-L1 and PD-L2, thereby releasing PD-1 pathway mediated inhibition of the immune response, including anti-tumor immune response. RTKs have been implicated in mediating an immunosuppressive tumor microenvironment, which has emerged as a potential resistance mechanism to checkpoint inhibitor therapy. Inhibition of these RTKs by sitravatinib may augment anti-tumor immune response and improve outcomes by overcoming resistance to checkpoint inhibitor therapy.

Eligibility: Inclusion Criteria:
  -  Diagnosis of Non-Squamous Non-Small Cell Lung Cancer
  -  Receipt of prior first-line treatment with platinum-based chemotherapy in combination with PD-1/PD-L1 checkpoint inhibitor therapy
  -  Adequate bone marrow and organ function
  -  Candidate to receive docetaxel as second line therapy
  Exclusion Criteria:
  -  Uncontrolled brain metastases
  -  Tumors that have tested positive for EGFR, ROS1, ALK mutations, or ALK fusions
  -  Unacceptable toxicity with prior checkpoint inhibitor therapy
  -  Receipt of systemic anti-cancer therapy post checkpoint inhibitor therapy, other than maintenance chemotherapy in the first-line setting
  -  Impaired heart function

Relevance to patient case: not relevant
Patient case: 54-year-old female with non-small cell lung cancer; genetic feature: EGFR (D770N)

Clinical trial: TKI Followed by Thoracic Radiotherapy for Stage IV EGFR Mutant NSCLC

Summary: In this phase II trial with single arm, we aim to investigate the clinical efficacy and toxicity profile of local radiotherapy on all disease sites for EGFR-mutant oligo-metastatic NSCLC (no more than 3 metastatic lesions) who did not experience disease progression after at least 3 months of TKI therapy.

Detailed description: Tyrosine kinase inhibitor (TKI) has been widely accepted as the first-line therapy for stage IV NSCLC with active mutation of EGFR. Olio-metastasis is a disease status between localized and extended status of disease, namely with the limited number of lesions, which is generally defined as ≤ 5. A couple of phase II studies have shown that consolidation local management was able to prolong the local-regional tumor control and might further improve overall survival (OS) for oligo-metastatic NSCLC who have gained disease control from systemic therapy. However, there is lack of data regarding whether local radiotherapy (RT) could improve progression free survival (PFS) and OS for NSCLC with active EGFR mutation who have benefited from TKI. In this phase II trial with single arm, we aim to investigate the clinical efficacy and toxicity profile of local radiotherapy on all disease sites for EGFR-mutant oligo-metastatic NSCLC (no more than 3 metastatic lesions) who did not experience disease progression after at least 3 months of TKI therapy.

Eligibility: Inclusion Criteria:
  -  Age ≥18 and ≤75;
  -  ECOG performance status 0-1;
  -  Patients must provide study specific informed consent prior to study entry;
  -  Pathologically or cytologically diagnosed as NSCLC;
  -  EGFR activating mutation to TKI approved by histology, cytology or circulation tumor DNA;
  -  Stage IV NSCLC with ≤ 3 metastatic lesions (AJCC, 8th ed.) confirmed by meticulous radiographic examination. Brain MRI and 18F PET/CT is strongly recommended unless there is a contraindication;
  -  Patients have received≥3 months of TKI therapy and do not received disease progression;
  -  HB ≥ 10.0 g/dL;
  -  Absolute number of neutrophil granulocyte ≥ 1.5 × 109/L;
  -  Absolute number of PLT ≥ 100 × 109/L;
  -  Total bilirubin ≤ 1.5 folds of the maximum extent;
  -  ALT and AST ≤ 2.0 folds of the maximum extent;
  -  Cr ≤ 1.25 folds of the maximum extent and Ccr ≥ 60mLl/min.
  Exclusion Criteria:
  -  Patients have received thoracic radiotherapy before;
  -  Malignant pleural effusion, pericardial effusion or peritoneal effusion;
  -  Patients have severe pulmonary comorbidity, such as ILD, COPD or other active pulmonary disease;
  -  Any unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, CHF (NYHA ≥ II), MI within 6 months of enrollment, severe arrhythmia requiring medication，hepatic, nephric or metabolic disease;
  -  HIV infection；
  -  Pregnancy or lactation women;
  -  ECOG status ≥2；
  -  Mixed SCLC component;
  -  Other factors that is considered ineligible.

Relevance to patient case: possibly relevant
Patient case: 54-year-old female with non-small cell lung cancer; genetic feature: EGFR (D770N)

Clinical trial: Korea Osimertinib Real World Evidence Study to Assess Safety and Efficacy - PLUS

Summary: This is a local, prospective, non-interventional, regulatory postmarketing surveillance study. The objectives of this study are to assess the safety and efficacy of single agent Tagrisso (Osimertinib, hereinafter "the study drug") in a real world setting according to the approved label in Korea.

Detailed description: -  Primary objective: To assess safety of the study drug for EGFR-tyrosine kinase inhibitor (TKI) naïve patients with locally advanced or metastatic, EGFR exon 19 deletions or exon 21 (L858R) substitution mutation-positive NSCLC, patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC who have been previously treated with EGFR TKI therapy in Korea
  -  Secondary objective: To assess efficacy of the study drug for EGFR-tyrosine kinase inhibitor (TKI) naïve patients with locally advanced or metastatic, EGFR exon 19 deletions or exon 21 (L858R) substitution mutation-positive NSCLC, patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC who have been previously treated with EGFR TKI therapy in Korea

Eligibility: -  Inclusion Criteria:
  1. Eligible for, or on active study drug treatment according to the approved label; The first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations, Treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC who have been previously treated with EGFR TKI therapy
  2. Provision of signed and dated written informed consent by the patient or legally acceptable representative
  -  Exclusion Criteria:
  1. History of hypersensitivity to the active substance or to any of the excipients of this drug
  2. Pregnancy and/or breast feeding
  3. Current participation in any interventional trial

Relevance to patient case: possibly relevant
Patient case: 54-year-old female with non-small cell lung cancer; genetic feature: EGFR (D770N)

Clinical trial: Afatinib as 2nd-line Treatment of Patients With EGFR Overexpression or EGFR Amplification ESCC (ESCC-A01)

Summary: This is a phase 2 trial investigating the effect of afatinib as second-line treatment of patients with EGFR overexpression or EGFR amplification esophageal Squamous Cell Carcinoma.


Eligibility: Inclusion Criteria:
  1. Having signed informed consent.
  2. Age 18 to 70 years old.
  3. Histologically confirmed esophageal squamous carcinoma
  4. Immunohistochemistry confirmed EGFR(3+) or EGFR-FISH-amplification or next generation sequencing confirmed EGFR-amplification.
  5. Computed tomography (CT) or magnetic resonance imaging (MRI) confirmed unresectable metastasic or recurrent ESCC.
  6. Failed to first-line treatment.
  7. Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria(diameter of the lesion should be more than 10mm by spiral CT or MRI, more than 20mm by common CT, the date of image should be less than 21 days before enrollment)
  8. Life expectancy of ≥3 month
  9. Eastern Cooperative Oncology Group (ECOG) 0-2
  10. WBC>3,000/mm3, absolute neutrophil count ≥1500/mm3, platelet>100,000/mm3, Hb>9g/dl，Bilirubin level < 1.5 times ULN，Serum creatinine <1.5 times ULN，ALT and AST<2.5 times ULN ，AKP < 2.5 times ULN ，(≤5 times ULN in patients with liver metastases)(within 7 days before enrollment)
  11. No sever complication, such as active gastrointestinal bleeding, perforation, jaundice, obstruction, non-cancerous fever＞38℃.
  12. Good compliance
  Exclusion Criteria:
  1. Contraindications of afatinib.
  2. Unable to take afatinib orally because of esophageal stenosis.
  3. Currently receiving other effective regimens.
  4. Previous anticipate other clinical trial within 4 weeks before entering this study.
  5. No measurable lesions, eg. pleural fluid and ascites.
  6. With other malignancy within 5 year, except non-melanoma skin cancer and cervical carcinoma in situ.
  7. Heart failure or other sever organ dysfunction, eg. coronary artery disease, myocardial infarction within the last 6 months.
  8. Mentally abnormal or disable cognition,including central nervous system (CNS) metastasis.
  9. HIV infection, active hepatitis B or hepatitis C.
  10. Unstable systemic diseases such as poorly controlled diabetes.
  11. Interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease showed in X-ray/CT.
  12. Keratitis, ulcerative keratitis or severe dry eye syndrome. Known hypersensitivity to study drug.
  13. Pregnancy or lactation period.
  14. Active severe infection within 14 days.

Relevance to patient case: not relevant
Patient case: 54-year-old female with non-small cell lung cancer; genetic feature: EGFR (D770N)

Clinical trial: K-RAS and EGFR in Lung Cancer

Summary: Retrospective analysis where patients with histologically confirmed Non-small cell lung cancer (NSCLC) were centrally evaluated for the presence of KRAS and EGFR mutations.

Detailed description: A retrospective analysis, performed by the Hellenic Co-operative Oncology Group (HeCOG), in samples from patients with histologically confirmed NSCLC, who had been treated within HeCOG-affiliated centres from March 2000 through December 2012, were centrally evaluated for the presence of KRAS and EGFR mutations. All patients had available clinicopathological data at diagnosis. Formalin-fixed, paraffin-embedded tissue blocks were retrospectively retrieved from the HeCOG tumor repository. Cytologic material was prospectively submitted for genotyping in more recent years (2010-2012).

Eligibility: Inclusion Criteria:
  -  Patients with histologically confirmed NSCLC
  -  Signed and dated written informed consent
  -  Age 18 years
  -  Available cytological material
  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: Video-Assisted Surgery in Treating Patients With Non-small Cell Lung Cancer

Summary: RATIONALE: Video-assisted surgery may be an effective treatment and have fewer side effects than conventional surgery in patients with non-small cell lung cancer.
  PURPOSE: Phase II trial to study the effectiveness of video-assisted surgery in treating patients who have non-small cell lung cancer.

Detailed description: OBJECTIVES: I. Determine the feasibility of performing video-assisted thoracic surgery (VATS) lobectomy, without significant morbidity or perioperative mortality, in patients with small (no greater than 3.0 cm), peripheral, non-small cell lung cancer. II. Determine the rate at which a thoracotomy must be carried out to complete a VATS lobectomy in these patients. III. Describe the complications associated with this procedure. IV. Describe the length of the operative procedure, duration of chest tube stay, and length of hospitalization in this patient population. V. Describe the survival and failure-free survival, over a 5-year period, in this patient population following this procedure.
  OUTLINE: Patients undergo video-assisted thoracic surgery (VATS) lobectomy, which requires 3 small incisions on the side of the chest. The entire anatomic pulmonary lobe is removed, as well as all peribronchial lymph nodes and anterior hilar lymph nodes. If it is not possible to remove the lobe using the VATS approach, then 1 of the incisions is converted to a standard thoracotomy. Patients are followed every 4 months for the first 2 years, and then every 6 months for the next 3 years.
  PROJECTED ACCRUAL: A total of 135 patients will be accrued for this study within 3 years.

Eligibility: DISEASE CHARACTERISTICS: Suspected or histologically documented non-small cell lung cancer Solitary, peripheral lung lesion that is no greater than 3.0 cm No metastatic disease No positive lymph nodes at mediastinoscopy At least 5 years since diagnosis of non-small cell or small cell lung cancer
  PATIENT CHARACTERISTICS: Age: Not specified Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Pulmonary: FEV1 at least 1.0 L or at least 50% of predicted Other: No significant comorbid medical or psychiatric condition No other active malignancy other than nonmelanomatous skin cancer
  PRIOR CONCURRENT THERAPY: Not specified

Relevance to patient case: not relevant