araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Sorafenib for Imatinib/Sunitinib-failed GIST

Summary: With discovery of KIT (CD117) mutations and the advent of KIT tyrosine kinase inhibitor imatinib, there has been substantial improvement in overall survival in patients with advanced and/or metastatic gastrointestinal tumors (GIST). Recently, sunitinib showed activity as second-line therapy in GIST patients after failure with imatinib. However, virtually all patients will eventually progress or become intolerable after imatinib and sunitinib. In preclinical models, sorafenib inhibits KIT activity and cell growth of imatinib-resistant tumors. The objective of this multi-center, non-randomized phase II study is to evaluate the safety and activity of sorafenib given as third-line therapy for GIST.

Detailed description: This is a non-randomized, open-label, multi-center, phase II study recruiting patients with advanced GIST who are pretreated with both imatinib and sunitinib. The current study will provide an estimate of the activity and safety of sorafenib in GIST. The primary study endpoint is the disease control rate (DCR), defined as complete or partial response or stable disease of at least 24 weeks of sorafenib therapy. Secondary endpoints include PFS, OS and safety.
  Patients with advanced (unresectable and/or metastatic) GIST who failed after previous therapy involving both imatinib and sunitinib will be eligible. Failure to imatinib and sunitinib is defined as disease progression regardless of intervening response during therapy, or intolerance. There is no limit to the number of prior therapies a patient may have received (e.g., patients may have received therapy with nilotinib, other TKIs, or chemotherapy in addition to imatinib or sunitinib).

Eligibility: Inclusion Criteria:
  -  age over 18 years
  -  advanced GIST
  -  failed (progressed and/or intolerable) after prior treatments for GIST
  -  ECOG performance status of 0~2
  -  resolution of all toxic effects of prior treatments
  -  no prior radiotherapy within 1 month before registration
  -  measurable lesion as defined by RECIST
  -  adequate marrow, hepatic, renal and cardiac functions
  -  provision of a signed written informed consent
  Exclusion Criteria:
  -  severe co-morbid illness and/or active infections
  -  pregnant or lactating women
  -  history of other malignancies
  -  active CNS disease not controllable with radiotherapy or corticosteroids
  -  active and uncontrollable bleeding from gastrointestinal tract
  -  prior history of sorafenib use
  -  gastrointestinal obstruction or malabsorption syndrome

Relevance to patient case: definitely relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Study of Nilotinib in Metastatic Melanoma With KIT Aberrations

Summary: Major response was observed to imatinib mesylate in KIT-mutated metastatic rectal melanoma (Hodi FS et al, J Clin Oncol 26:2046-2051, 2008). In the ASCO annual meeting in 2009ar, KIT mutations were reported to be present in 23% of acral and 15.2% of mucosal melanomas (Heinrich MC et al, J Clin Oncol 26:2008 abstr 9016). Nilotinib is a novel tyrosine kinase inhibitor (TKI) targeting KIT, PDGFR, and Bcr-Abl and inhibiting the proliferating of both imatinib-sensitive and imatinib-resistant cells in vitro. Phase I study of nilotinib alone and in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors (GIST) demonstrated significant activity (72% stable disease for nilotinib alone and 56% for nilotinib/imatinib combination) (Blay JY et al, J Clin Oncol 26:2008, abstr 10553).
  Thus, we propose to conduct a phase II study of nilotinib in metastatic melanoma with KIT mutations.


Eligibility: Inclusion Criteria:
  1. Histologically or cytologically proven melanoma with stage IV or unresectable stage III disease
  2. Documented KIT aberration
  3. Adequate organ function as defined by the following criteria:
  -  Serum aspartate transaminase (AST); serum glutamic oxaloacetic transaminase (SGOT)) and serum alanine transaminase (ALT); serum glutamic pyruvic transaminase (SGPT)) ≤ 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy
  -  Total serum bilirubin ≤ 1.5 x ULN
  -  Absolute neutrophil count (ANC) ≥ 1500/µL
  -  Platelets ≥ 100,000/µL
  -  Hemoglobin ≥ 9.0 g/dL (may be transfused or erythropoietin treated)
  -  Serum calcium ≤ 12.0 mg/dL
  -  Serum creatinine ≤ 1.5 x ULN
  4. Patients with CNS metastasis must have stable neurologic function without evidence of CNS progression within 8 weeks
  5. May have previous adjuvant therapy with interferon, vaccines or therapy with IL-2, chemotherapy
  6. At least one measurable lesion by RECIST criteria
  7. ECOG PS 0-2
  Exclusion Criteria:
  1. Major surgery or radiation therapy within 4 weeks of starting the study treatment.
  2. History of or known carcinomatous meningitis, or evidence of symptomatic leptomeningeal disease on screening CT or MRI scan.
  3. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2.
  4. QTc > 470 msec on baseline EKG.
  5. Pregnancy or breastfeeding.

Relevance to patient case: not relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

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: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

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: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

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: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

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: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib

Summary: The purpose of this study is to evaluate the efficacy and safety of Dovitinib in patients with gastrointestinal stromal tumors refractory and/or intolerant to Imatinib


Eligibility: Inclusion Criteria:
  -  Histologically confirmed GIST of any anatomical location, which is 1) unresectable and/ or metastatic with documented disease progression while on therapy with imatinib or 2) surgically removed localized GIST, recurrent on adjuvant imatinib or recurrent within the first 3 months after discontinuation of adjuvant imatinib or 3) patients with unresectable and/or metastatic GIST intolerant to imatinib
  -  Positive immunohistochemical staining for c-KIT (CD117); or negative staining for KIT, but with either positive staining for DOG1 or an identified mutation of KIT or PDGFRA gene
  -  Documented disease progression according to RECIST (version 1.1) on prior therapy with imatinib at a dose of at least 400mg/day or patients with unresectable and/or metastatic GIST who are intolerant to imatinib
  -  At least one measurable GIST lesion according to RECIST (version 1.1).
  -  Adequate bone marrow, liver and renal function
  Exclusion Criteria:
  -  Patients who have received any other tyrosine-kinase inhibitor but imatinib for GIST
  -  Patients who received cytotoxic drugs ≤ 4 weeks prior to starting Dovitinib (TKI258)
  -  Patients who are treated or planned to be treated concomitantly with other cytotoxic or antineoplastic treatments, such as chemotherapy, immunotherapy, biological response modifiers, or radiotherapy
  -  Patients with another primary malignancy within 3 years prior to starting the study drug
  -  Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic) ≤ 4 weeks prior to starting Dovitinib (TKI258) or who have not recovered from the adverse effects of such therapy
  -  Patients with a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) within the past 6 months
  -  Patients with impaired cardiac function or clinically significant cardiac diseases
  -  Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Dovitinib
  -  Patients with prior complete gastrectomy
  -  Patients with brain metastasis or history of brain metastasis
  -  Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin or equivalent anticoagulant
  -  Pregnant or breast-feeding women
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: definitely relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Study on the Evolution of Genes Mutation Related With Gastrointestinal Stromal Tumors

Summary: Mutations of tumor-related genes are dynamic. Gastrointestinal stromal tumor cells often are obviously more invasive in case of recurrence. The great majority of relapses may be associated with secondary mutation in the GIST related genes. Full gene sequences of c-KIT、PDGFRA and DOG1, which is extracted from the specimen cells of repeated surgical resection or biopsy tissue in GIST patients with postoperative recurrence, are analyzed with the screening-sequencing approach, in order to investigate the characteristics and variations associated with the different gene mutations of c-KIT、PDGFRA and DOG1 in GIST patients and be likely to find out the evolutionary pattern, try to learn the facts about the effect of tyrosine kinase inhibitors on the GIST related genes, make a survey of any association of c-KIT、PDGFRA and DOG1 gene mutations and provide the basis for seeking molecular marker of GIST for monitoring course of disease, and offer a theoretical basis and new therapeutic strategies for application of clinical treatment.


Eligibility: Inclusion Criteria:
  -  patients with Gist at the Department of Gastrointestinal and Glands Surgery of the First Affiliated Hospital of Guangxi Medical University in China.
  Exclusion Criteria:
  -  patients with hepatitis and tuberculosis

Relevance to patient case: definitely relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Masitinib in Patients With Gastro-Intestinal Stromal Tumour Resistant to Imatinib

Summary: The objective is to compare efficacy and safety of masitinib at 12 mg/kg/day to sunitinib at 50 mg/day in treatment of patients with gastro-intestinal stromal tumor resistant to imatinib.


Eligibility: Inclusion Criteria:
  1. Histological proven, metastatic, or locally advanced and non-operable GIST
  2. Measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST criteria
  3. C-kit (CD117) positive tumors detected immuno-histochemically and documented mutation of c-kit at any time if available
  4. Patients resistant to imatinib at dose of 400 mg/day
  Exclusion Criteria:
  1. Patient treated for a cancer other than GIST cancer within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ
  2. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis

Relevance to patient case: definitely relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib

Summary: Patients with metastatic or locally advanced gastrointestinal stromal tumors (GIST) who develop resistance against the two hitherto approved drugs for this disease, the tyrosin kinase inhibitors (TKIs) imatinib and sunitinib, have a poor prognosis. Sometimes a further response may be achieved by other drugs, mainly other TKIs, which have been explored in different studies but not yet have been approved for clinical use. Pazopanib is a TKI inhibiting the tyrosin kinases KIT, PDGFRA, and VEGF 1-3, all of which have important roles in the pathogenesis of GIST. Theoretically, it may function in GIST, and it deserves investigational trials. The drug is approved for metastatic renal cancer and is relatively well tolerated. In this trial (SSG XXI), the disease control rate (DCR) = (CR+PR+SD) after 12 weeks of treatment will be assessed as the primary endpoint, and at the same time trough levels will be measured. Secondary endpoints include ORR, PFS, toxicity, and disease control rate in relation to trough level week 12 and in relation to the primary mutation of the tumor (if known). The goal is to include 72 patients in the trial, which is open and single arm.


Eligibility: Eligibility Criteria:
  -  Metastatic and/or locally advanced GIST, with diagnosis based on histology with positive c-kit and/or DOG-1, or with a GIST-typical mutation in KIT or PDGFR
  -  Measurable disease on CT (computed tomography) as defined by RECIST criteria; at least one measurable lesion not given radiotherapy
  -  History of progressive disease on CT according to RECIST criteria after both imatinib and sunitinib treatment, and also after nilotinib if this drug has been given
  -  No other TKIs given than imatinib, sunitinib and nilotinib
  -  Age at least 18 years at the time of diagnosis of GIST
  -  WHO performance status 0-2
  -  Resolution of all toxic side effects from earlier TKI treatment and any other potential non-TKI treatment to grade 1 or below
  -  Sufficient organ functions as defined in the protocol
  -  Absence of earlier or present certain other conditions as defined in the protocol
  -  No pregnancy or lactation
  -  Women with childbearing potential must accept the use of adequate contraception throughout the study period
  -  Written informed consent

Relevance to patient case: definitely relevant
Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Masitinib in Patients With Gastrointestinal Stromal Tumour After Progression With Imatinib

Summary: The objective is to compare the efficacy and safety of masitinib at 12 mg/kg/day to sunitinib at 50 mg/day in the treatment of patients with gastro-intestinal stromal tumor (GIST) after progression with imatinib.

Detailed description: Masitinib is a selective tyrosine kinase inhibitor with potent activity against wild-type c-Kit, the juxta membrane domain of c-Kit, and PDGFR. Masitinib is also thought to promote survival via modulation of immunostimulation-mediated anticancer effects and modulation of the tumor microenvironment. The objective is to compare the efficacy and safety of masitinib at 12 mg/kg/day with respect to sunitinib at 50 mg/day in the treatment of imatinib-resistant gastro-intestinal stromal tumor (GIST).

Eligibility: Main inclusion criteria include:
  -  Patient with histological proven metastatic GIST or non-operable locally advanced GIST
  -  Patient with c-Kit (CD117) positive tumor detected immuno-histochemically
  -  Patient after at least one progression with imatinib at a dose up to 800mg. Progression is defined as a RECIST 1.1 and/or CHOI disease progression while receiving imatinib treatment.
  Main exclusion criteria include:
  -  Patient treated for a cancer other than GIST within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ
  -  Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
  -  Pregnant, or nursing female patient

Relevance to patient case: definitely relevant