araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Rechallenge of Imatinib in GIST Having no Effective Treatment

Summary: The objective of this study is to compare the clinical outcomes following resumption of dosing (re-challenge) with Imatinib plus best supportive care versus placebo plus best supportive care in patients with advanced/incurable Gastrointestinal Stromal Tumors following failure of prior imatinib and sunitinib therapies.


Eligibility: Inclusion Criteria:
  -  Patients aged 18 years and older
  -  Patients with metastatic or unresectable malignant gastrointestinal stromal tumour which has been histologically confirmed by the detection of CD117 on immunohistochemical staining or genetically confirmed by the detection of mutation in KIT or PDGFRα genes on direct sequencing of tumor DNA.
  -  Prior benefit from 1st line imatinib defined as complete response, partial response, or stable disease at 6 months after the start of 1st line imatinib
  -  Patients whose disease has progressed despite at least both prior imatinib therapy (400mg/day) and then subsequently also failure of prior sunitinib therapy.
  -  ECOG(Eastern Cooperative Oncology Group) performance status 0 ~ 3
  -  Adequate bone marrow function as defined by platelets ≥ 75 x 109/L and neutrophils ≥ 1.5 x 109/L
  -  Adequate renal function, with serum creatinine < 1.5 x upper limit of normal
  -  Adequate hepatic function with serum total bilirubin < 1.5 x upper limit of normal, alanine aminotransferase or aspartate aminotransferase < 2.5 x upper limit of normal in the absence of liver metastases, or < 5 x upper limit of normal in the presence of liver metastases.
  -  Expected life expectancy of greater than 12 weeks in the absence of any intervention
  -  No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer except where treated with curative intent > 5 years previously without evidence of relapse
  -  Written, informed consent to the study
  Exclusion Criteria:
  -  Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non- compliance
  -  Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy
  -  Obstruction of gastrointestinal tract
  -  Active gastrointestinal bleeding
  -  Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
  -  Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol
  -  Female patients who are pregnant or breast-feeding. Female patients must have had a negative pregnancy test within one week before starting imatinib.

Relevance to patient case: definitely relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: A Retrospective Study of C-kit Mutation Status in Asian Patients With Advanced Gastro-intestinal Stromal Tumors (GIST) Treated With Imatinib.

Summary: Imatinib is the current standard treatment for advanced GIST. Previous studies have shown that GIST genotype was associated with treatment outcomes with exon 11 having superior outcome compared with exon 9 or WT.10, 11 In patients with exon 9 kit mutation, the response rate was higher at when imatinib was given at 800mg daily compared with the standard dose of 400mg daily. Although the data linking tyrosine kinase mutation status and imatinib response in metastatic GISTs is intriguing, more information is needed before mutation testing is adopted as part of the routine analysis of high-risk or overtly malignant KIT-expressing GISTs.25 Despite the fact that exon 9 mutations are associated with a lower response rate, overall survival does not appear to be better with high-dose therapy. The investigators propose to conduct a retrospective analysis of mutational analysis on patients with GIST and determine the relationship between patient response and imatinib dose.


Eligibility: Inclusion Criteria:
  1. Histologic diagnosis of advanced stage or metastatic GIST
  2. Asian patient (as defined by the investigator)
  3. First line treatment with imatinib
  4. Availability of tumor samples for kit mutation analysis
  5. Availability of tumor response rate and or time to progression data
  Exclusion Criteria:
  -

Relevance to patient case: definitely relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: A Study to Assess the Incidence of EGFR Mutation in Patients With Newly Diagnosed Locally Advanced or Metastatic Non-Small Cell Lung Cancer in the UK, And of Tarceva (Erlotinib) as First-Line Therapy in EGFR Mutation Positive Patients.

Summary: This study will assess the prevalence of epidermal growth factor receptor (EGFR) mutations in newly diagnosed patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Patients with positive EGFR mutation results will enter an open-label, single arm study to evaluate progression-free survival and quality of life with first-line Tarceva (erlotinib) therapy. Patients will receive Tarceva at a dose of 150 mg orally daily. Anticipated time on study treatment is until progressive disease or unacceptable toxicity occurs. Patients with negative EGFR mutation results will be offered treatment as per the centre's standard of care.


Eligibility: Inclusion Criteria:
  -  Adult patients, >/= 18 years of age
  -  Locally advanced or metastatic (stage IIIB/IV) non-small cell lung cancer (NSCLC)
  -  ECOG performance status 0-3
  -  Treatment phase: histologically confirmed EGFR exon 19 deletion or exon 21 mutation in the diagnostic phase of the study
  -  Adequate haematological, liver and renal function
  -  Female patients must be postmenopausal, surgically sterile, or agree to use a barrier method of contraception
  -  Male patients must be surgically sterile or agree to use a barrier method of contraception
  Exclusion Criteria:
  -  Previous treatment for NSCLC with chemotherapy or therapy against EGFR, either with antibody or small molecule (tyrosine kinase inhibitor)
  -  Symptomatic cerebral metastases
  -  Pregnant or lactating women
  -  Any other concomitant anti-cancer therapy (until disease progression and discontinuation of Tarceva therapy)

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Masitinib in Non-Resectable or Metastatic Stage 3/4 Melanoma Carrying a Mutation in the Juxta Membrane Domain of c-Kit

Summary: The objective is to assess the efficacy and safety of masitinib at 7.5 mg/kg/day in the treatment of patients with non-resectable or metastatic stage 3 or stage 4 melanoma carrying a mutation in the juxta membrane domain of c-Kit and who have not previously been treated for melanoma.

Detailed description: Masitinib is a selective tyrosine kinase inhibitor with potent activity against the juxta membrane domain of c-Kit. Masitinib is also thought to promote survival via modulation of immunostimulation-mediated anticancer effects and modulation of the tumor microenvironment. The objective of this study was to evaluate the efficacy and safety of masitinib with respect to dacarbazine in the treatment of non-resectable or metastatic stage 3 or stage 4 melanoma carrying a mutation in the juxta membrane domain of c-Kit. Following a protocol amendment, the dacarbarzine treatment group was closed and recruitment restricted to masitinib treatment of chemo-naïve (first-line) patients.

Eligibility: Main inclusion criteria include:
  -  Patient with histologically or cytologically confirmed non-resectable or metastatic stage 3 (non-resectable IIIB or IIIC, AJCC TNM staging system 7th edition) or stage 4 melanoma
  -  Patient with detectable c-Kit JM mutation (mutation in exon 9, 11 or 13) confirmed by DNA or RNA sequencing, which is expected to be mainly found after screening of mucosal or acral melanoma or melanoma on skin with chronic sun-induced damages (defined by a microscopically marked elastosis involving the skin surrounding their primary melanoma).
  -  Patient not previously treated for melanoma (first-line)
  Main exclusion criteria include:
  -  Pregnant, or nursing female patient
  -  Patient with active brain metastases.
  -  Prior treatment with a tyrosine kinase c-Kit inhibitor

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Role of Epoxy-eicosatrienoic Acids in Post-occlusive Hyperemia and Thermal Hyperemia

Summary: The objective of this proof of concept study is to assess the involvement of epoxy-eicosatrienoic acids (EETs) in post-occlusive hyperemic and thermal hyperemia responses, and the interaction between nitric oxide (NO) and EETs, using the latest methods for the study of functional microcirculation.

Detailed description: The EETY study is a single-center proof of concept study in healthy volunteers. The main objective is to study the involvement of epoxy-eicosatrienoic acids (EETs) in the reactivity of cutaneous microcirculation during post-occlusive hyperemia and thermal hyperemia, by studying the response to microdialysis of fluconazole (an inhibitor of EETs) versus control, on the forearm.
  Response is measured by the amplitude of the post-occlusive hyperemia and thermal hyperemia peaks (maximum amplitude as a percentage of maximal vasodilation and areas under the curve: AUC) during the injection of fluconazole compared to an intradermal injection of solvent (NaCl 9 ‰).
  The subjects are healthy volunteers of both sexes, aged between 18 and 35, non-smokers and in good health. Over two years, 30 subjects will be included in the study for 6 to 13 weeks.

Eligibility: Inclusion Criteria:
  -  Age between 18 and 35 years
  -  Affiliated to the French social security system or beneficiary a similar regime
  -  In good health
  Exclusion Criteria:
  -  Active smoker
  -  Pregnant, parturient, breast-feeding
  -  Person deprived of civil liberties by judicial or administrative measure; person under legal protection,
  -  Minor less than 18 years
  -  Within period exclusion for other clinical research studies
  -  Person has exceeded the annual compensation for participation in trials
  -  Person with active disease or with prolonged treatment, excluding oral contraceptives and paracetamol
  -  Asthma, urticaria, angioedema, known drug allergy

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: A Study of Olaratumab (IMC-3G3) in Previously Treated Participants With Unresectable and/or Metastatic Gastrointestinal Stromal Tumors

Summary: The purpose of this study is to evaluate the tumor response of stable disease (SD), partial response (PR), or complete response (CR) [according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1 criteria)] at 12 weeks in participants with Gastrointestinal Stromal Tumors (GIST) harboring platelet-derived growth factor receptor alpha (PDGFRα) mutations and patients with GIST not harboring PDGFRα mutations.


Eligibility: Inclusion Criteria:
  -  Participant has histologically or cytologically confirmed, unresectable and/or metastatic GIST
  -  Participant has measurable disease
  -  Participant has documented objective progression following, or intolerance to, treatment with both imatinib and sunitinib
  -  Participant's Eastern Cooperative Oncology Group (ECOG) performance status (PS) is 0 to 2
  -  Participant has either:
  1. prior results from growth factor receptor associated with tyrosine kinase activity (KIT) and PDGFRα mutation analysis that meet analytical criteria as defined for the on-study analysis of these mutations and tumor tissue (from either primary or metastatic tumor) that can be submitted for analysis within 30 days after the first dose of study therapy; or
  2. if prior results from KIT and PDGFRα mutation analysis are not available or do not meet analytical criteria as above, then tumor tissue (from either primary or metastatic tumor) must be submitted for genotype testing at the latest 28 days prior to the first dose of study therapy
  -  Participant has adequate hematologic, hepatic, renal and coagulation function
  -  Women of childbearing potential and sexually active males must agree to use adequate contraception prior to study and for at least 12 weeks after the last dose of IMC-3G3
  -  Participant has a life expectancy of ≥ 3 months
  Exclusion Criteria:
  -  Participant has untreated central nervous system metastases, and as a result, is clinically unstable with regard to neurologic function
  -  Participant has a history of another primary cancer
  -  Participant has received any investigational therapy within 14 days prior to registration, or is currently enrolled in any other type of medical research
  -  Participant is receiving concurrent treatment with other anticancer therapy
  -  Participant has known human immunodeficiency virus (HIV) infection
  -  Participant has undergone major surgery within 28 days prior to registration
  -  If female, participant is pregnant or breastfeeding

Relevance to patient case: definitely relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Dose Escalation Study of BIBF 1120 in Combination With Carboplatin and PLD in Relapsed Ovarian Cancer (OC)

Summary: This phase I, open label dose escalation study will investigate the addition of BIBF 1120 to treatment with the combination of carboplatin and Pegylated Liposomal Doxorubicin (PLD) in patients with advanced, platinum sensitive relapsed ovarian cancer, fallopian tube carcinoma or primary peritoneal cancer. Patients will be treated with BIBF 1120 together with carboplatin and PLD in up to 6-9 repeated 28 days treatment courses until disease progression is observed.


Eligibility: Inclusion criteria:
  1. Female patients, age 20 years or older, with relapse of histologically (on initial diagnosis) confirmed epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal cancer
  2. Up to 3 lines of prior chemo therapy, with treatment free interval of >6 months
  3. Platinum based chemotherapy in the immediately preceding line.
  4. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1
  5. Written informed consent that is consistent with Good Clinical Practice (GCP) guidelines
  Exclusion criteria:
  1. Prior chemotherapy with PLD, and any contraindication for therapy with carboplatin or PLD.
  2. More than 2 lines of prior therapies that contained angiogenesis inhibitor.
  3. Patients for whom surgery is planned, e.g. interval debulking surgery.
  4. History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months.
  5. Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal) or antiviral therapy.
  6. Laboratory values indicating an increased risk for adverse events.
  7. Significant cardiovascular diseases.

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: A Study of Sunitinib In Young Patients With Advanced Gastrointestinal Stromal Tumor

Summary: Children and young adults with gastrointestinal stromal tumors (GIST) will be treated with sunitinib. The safety (including pharmacokinetics) and tolerability of sunitinib will be studied in these patients. In addition, tumor responses and overall survival will be assessed.


Eligibility: Inclusion Criteria:
  -  Histological diagnosis of GIST.
  -  Patients must have demonstrated either disease progression or intolerance to imatinib mesylate, have non-mutant Stem Cell Factor Receptor gene (KIT) GIST, or cannot obtain imatinib in their country
  -  Measurable by Response Evaluation Criterion in Solid Tumors (RECIST) or evaluable disease.
  Exclusion Criteria:
  -  Current treatment with another investigational agent.
  -  Prior sunitinib treatment.
  -  Prior therapy with known risk for cardiovascular complications.

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors

Summary: In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma and patients with other solid tumors will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide.

Detailed description: In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma (n=6) will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma (n=9) and patients with other solid tumors (n=6) will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide. AdCD40L is given by weekly injections of 2.5x10e11 VP, 4x; total dose 1x10e12 VP. A maximum of 30 patients will be included in this trial.
  AdCD40L is an adenoviral nonreplicating vector carrying the human CD40L gene. AdCD40L infects tumor cells upon intratumoral injection and deliver the CD40L gene into the cells whereupon the virus is destroyed. CD40L is then expressed as a membrane-bound protein and interacts with the CD40 receptor expressed by for example dendritic cells (DCs) in the tumor area. DCs mature upon CD40/CD40L interactions and activates tumor-specific T cell responses.

Eligibility: Inclusion Criteria:
  -  Histologically proven diagnosis of malignant solid cancer, ECOG 0-2.
  -  Disease progression on established treatments or patients not eligible to standard options.
  -  Signed informed consent must be obtained.
  Exclusion Criteria:
  -  Pregnancy.
  -  Life expectancy less than 3 months.
  -  Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
  -  Patients with severe systemic autoimmune disease.
  -  Patients that do not consent to that tissue and blood samples are stored in a biobank.

Relevance to patient case: not relevant
Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

Clinical trial: Detection of CF-DNA in Patients With Gastrointestinal Stromal Tumors (GIST)

Summary: Activating mutations of the kinases CKIT or PDGFRA can be detected in 90% of cases by DNA sequence analysis of a pathological specimen. These mutated genomic DNA fragments are highly specific for the tumor and are released by the tumor into the circulation. Allele-specific PCR can be used to specifically amplify and quantify mutated CKIT and PDGFR DNA fragments.
  The current trial aims to evaluate whether tumor DNA carrying mutations for CKIT and PDGFRA can be detected and quantified in the plasma of patients with active GIST, and whether detection can be correlated with the clinical course of disease either under therapy or in progressive disease irrespective of current therapy.


Eligibility: Inclusion Criteria:
  -  Signed written informed consent
  -  Male or female patients aged >= 18 years
  -  Histologically confirmed GIST
  -  Known activating mutation of CKIT or PDGFRA and tissue sample can be provided for central mutation analysis or mutation status unknown and tissue sample can be provided for central mutation analysis at baseline
  -  Routinely planned follow-up visits in no longer than three months intervals (+ 14 days) including local standard of care diagnostic imaging (CT, PET- CT, or MRI)
  -  At least one GIST lesion that can be measured by CT, PET-CT, or MRI
  -  Planned surgery of one or more disease manifestations or planned TKI treatment (such as imatinib or sunitinib) in neoadjuvant or palliative intention or disease progression irrespective of current/planned treatment
  -  Life expectancy of at least three months
  Exclusion Criteria:
  -  Wild type sequence for CKIT exon 9, 11, 13, 14, 17, 18 and PDGFRA exon 18
  -  Tissue sample can not be provided for central mutation analysis
  -  Surgery of primary or progressive lesions already completed and currently no evidence of progressive lesions
  -  Patients currently receiving adjuvant TKI treatment after surgery and no evidence of progressive lesions
  -  Patients currently receiving palliative TKI treatment and no evidence of progressive lesions
  -  Planned follow-up intervals including CT, PET-CT or MRI at more than three months intervals (+ 14 days)
  -  Coexisting medical condition or treatment that could interfere with the ability of the patient to comply with planned treatment interventions (surgery or TKI treatment) or regular follow-up visits
  -  Patients unwilling to or unable to comply with the planned therapeutic intervention (surgery or TKI treatment) or to comply with the regular follow-up visits including blood sample collection
  -  Pregnancy and lactation
  -  Presence of chronic inflammatory diseases, autoimmune diseases, or liver cirrhosis
  -  Known HIV and/or hepatitis B or C infection
  -  Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix and basal or squamous cell carcinoma of the skin

Relevance to patient case: definitely relevant