araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Safety And Efficacy Study Of Sunitinib Malate In Chinese Patients With Imatinib Resistant Or Intolerant Malignant Gastrointestinal Stromal Tumor

Summary: To investigate safety and efficacy of single agent sunitinib malate in Chinese Patients With Imatinib Resistant Or Intolerant Malignant Gastrointestinal Stromal Tumor.


Eligibility: Inclusion Criteria:
  -  Histologically-proven diagnosis of malignant GIST (Gastrointestinal Stromal Tumors).
  -  Evidence of unidimensionally measurable disease
  -  Failure of prior treatment with imatinib or intolerant to imatinib
  -  Male or female, 18 years of age or older.
  -  ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1.
  -  Resolution of all acute toxic effects
  -  Adequate organ function.
  Exclusion Criteria:
  -  Anticancer treatment after last dose of imatinib
  -  Major surgery within 4 weeks or radiation therapy within 2 weeks.
  -  Grade 3 hemorrhage within 4 weeks prior to starting the study treatment.
  -  Diagnosis of second malignancy within the last 5 years.
  -  History of brain disease.
  -  Cardiac disease within 12 months.
  -  Thyroid function abnormality.
  -  Ongoing cardiac dysrhythmias.
  -  Uncontrolled hypertension.
  -  Ongoing treatment with anticoagulant and CYP3A4 inhibitors and inducers.
  -  HIV or AIDS related illness.
  -  Pregnancy or breastfeeding.

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: A Prospective, Multicenter Study on Best Clinical Use of Imatinib in the Advanced Gastrointestinal Stromal Tumors

Summary: Open-label, multicenter study of imatinib (400mg/die p.o.)in patients with advanced gastrointestinal stromal tumors. Patients will be treated for up to 12 months. Data regarding its best clinical use in terms of tumor response, survival, tolerability and safety profile will be prospectively collected.


Eligibility: Inclusion Criteria:
  1. Patients ≥ 18 years of age.
  2. Histologically documented diagnosis of GIST, unresectable and/or metastatic and therefore incurable with any conventional multimodality approach.
  3. Immunohistochemical documentation of c-kit (CD117) expression by tumor, as detected on a tumor sample taken within 6 weeks of study entry.
  4. At least one measurable site of disease (RECIST Criteria), or other response assessment criteria, as appropriate.
  5. Performance status 0,1, 2 or 3 (ECOG).
  6. Adequate end organ function.
  7. Adequate bone marrow function.
  8. Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing.
  Exclusion Criteria:
  1. Previous treatment with any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing.
  2. Other primary malignancy with < 5 years clinically assessed disease free interval, except basal cell skin cancer, cervical carcinoma in situ, or other neoplasms judged after consultation with the Steering committee to entail a low risk of relapse.
  3. Grade III/IV cardiac problems as defined by the New York Heart Association Criteria.
  4. Pregnancy, breast-feeding.
  5. Severe and/or uncontrolled medical disease.
  6. Known brain metastasis.
  7. Known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
  8. Known diagnosis of human immunodeficiency virus (HIV) infection.
  9. Previous treatment with chemotherapy within 4 weeks (6 weeks for nitrosoureas or Mitomycin-C).
  10. Previous radiotherapy to ≥ 25 % of the bone marrow.
  11. Major surgery within 2 weeks prior to study entry.

Relevance to patient case: possibly relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Study of Tumor Samples in Patients Undergoing Treatment for Gastrointestinal Stromal Tumors on Clinical Trial ACOSOG-Z9001

Summary: RATIONALE: Studying the genes expressed in samples of tumor tissue from patients with cancer may help doctors identify biomarkers related to cancer.
  PURPOSE: This research study is looking at tumor samples in patients undergoing treatment for gastrointestinal stromal tumors on clinical trial ACOSOG-Z9001.

Detailed description: OBJECTIVES:
  Primary
  -  To examine polymorphisms in selected genes involved in the detoxifying/metabolizing and DNA repair pathways in relation to specific mutations and types of mutation in the c-kit gene in tumor tissue from patients with gastrointestinal tumors (GIST) undergoing treatment on clinical trial ACOSOG-Z9001.
  Secondary
  -  To examine approximately 758 polymorphisms among candidate genes involved in detoxification/metabolism, cell cycle control, and DNA damage/repair in relation to specific mutations and types of mutation in the c-kit gene in tumor tissue from GIST patients for hypothesis generation. (exploratory)
  -  To conduct an exploratory analysis of the polymorphism distribution in these patients. (exploratory)
  -  To examine the association between the above polymorphisms and major toxicity (Grade 3/4) of adjuvant imatinib mesylate. (exploratory)
  OUTLINE: Tumor samples are used for polymorphism and mutation analysis.

Eligibility: DISEASE CHARACTERISTICS:
  -  Tumor samples from patients with gastrointestinal stromal tumors enrolled on clinical trial ACOSOG-Z9001

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Nilotinib Pharmacokinetics (PK) in Gastrointestinal Stromal Tumor (GIST)

Summary: In patients who are receiving nilotinib, nilotinib plasma levels will be measured after 1 month of nilotinib treatment. The relationship between surgery type and nilotinib pharmakokinetic properties will be investigated in this study.


Eligibility: Inclusion Criteria:
  -  Patients with metastatic or unresectable gastrointestinal stromal tumor
  -  Patients receiving nilotinib after failure to imatinib and sunitinib

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: A Phase 2 Study to Evaluate Efficacy and Safety of Masitinib in Non Pre-treated, Inoperable Patients With Locally Advanced/Metastatic Gastro-intestinal Stromal Tumour (GIST)

Summary: The objective is to evaluate the efficacy and safety of AB1010 at 7.5 mg/kg/day in the treatment of non pre-treated, inoperable patients with locally advanced/metastatic GIST.


Eligibility: Inclusion Criteria:
  -  Male or Female patients, age >18
  -  Life expectancy > 6 months
  -  Histological proven, metastatic, or locally advanced and non-operable, non- pre-treated GIST.
  -  Patients having never received any tyrosine kinase inhibitor, including as adjuvant therapy
  -  C-Kit (CD117) positive tumors detected immuno-histochemically
  -  Measurable tumor lesions with longest diameter >20 mm using conventional techniques or >10 mm with spiral CT scan
  Exclusion Criteria:
  -  Documented allergy to the similar drug of AB1010
  -  Inadequate organ function
  -  Patients with a history of any other malignancy

Relevance to patient case: possibly relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: A Study of AMNN107 in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation

Summary: The purpose of this study is to determine whether nilotinib is efficacious in the treatment of metastatic and/or inoperable melanoma harboring a c-Kit mutation.

Detailed description: This trial began as a multi-center, randomized, Phase III, controlled trial for nilotinib vs (DTIC) dacarbazine to assess the efficacy and safety of nilotinib (400 mg bid) in patients with c-Kit mutated metastatic and/or inoperable melanoma. The study was open to patients with mucosal or acral melanoma.
  Due to substantial difficulties identifying and recruiting eligible patients, the trial design was altered from a randomized, two-arm, Phase III study to a single-arm, Simon two-stage Phase II study with protocol Amendment 2 (27-Jul-2011). While the original protocol required the recruitment of 120 patients, this amendment required the study to recruit only 41 patients (patients randomized to nilotinib prior to Amendment 2 were to be counted in this total, but those randomized to dacarbazine ( DTIC ) DTIC were not). Patients randomized to DTIC were allowed to cross-over to nilotinib, either immediately or at the time of progression.

Eligibility: Inclusion Criteria:
  1. Histologically confirmed mucosal or acral 2. Presence of a c-Kit mutation of exon 9, 11 or 13, or mutations Y822D and mutations D820Y, Y823D of exon 17, as confirmed by the central laboratory 3. Stage III unresectable or stage IV disease 4. The presence of one or more measurable lesions as detected by radiological or photographic methods and assessed according to RECIST 1.0. Lesions must have a size of at least 10mm at longest diameter (using a slice thickness of 5 mm)or double the slice thickness to be considered a target lesion. Target lesions should not be selected in previously irradiated fields unless there is clear evidence of progression 5. WHO performance status 0 - 2
  Exclusion Criteria:
  1. C-Kit mutation of exons 17(except mutations D820Y, Y822D or Y823D) or any other exon not allowed by the inclusion criteria
  2. Patients with c-Kit amplifications only and no mutation
  3. Patients with any history of brain metastases
  4. Patients who have had any prior treatment with TKIs
  5. Patients receiving medications or herbal extracts which interfere with nilotinib metabolism which are not discontinued by the time of the baseline visit
  6. Acute or chronic liver or renal disease considered unrelated to melanoma
  Other protocol-defined inclusion/exclusion criteria may have applied.

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Study of Dose Escalation Versus no Dose Escalation of Imatinib in Metastatic Gastrointestinal Stromal Tumors (GIST) Patients

Summary: The purpose of this study is to determine if escalating the dose of imatinib to keep the drug blood level at ≥ 1100 ng/ml leads to better outcomes for patients.


Eligibility: Inclusion Criteria:
  -  Age ≥ 18 years
  -  Unresectable and/or metastatic GIST
  -  Currently receiving imatinib 400 mg per day for a minimum of 4 weeks prior to registration, and for no more than 6 months prior to registration. This must be the first time that the patient has been treated for metastatic and/or unresectable GIST
  -  For patients who received imatinib following surgery at the time of an initial diagnosis of GIST, there must be a 6 month interval between completion of imatinib and the diagnosis of metastatic GIST
  -  Good physical functioning (ECOG Performance Status of 0 or 1)
  -  Generally, good function of organ such as liver and kidneys
  Exclusion Criteria:
  -  Disease progression during adjuvant therapy with imatinib (adjuvant treatment is treatment that is given after surgery for GIST)
  -  Known intolerance of imatinib at a dose of 400 mg/day or higher
  -  Prior systemic therapy for advanced GIST with imatinib or those who have been on imatinib for longer than 6 months for unresectable and/or metastatic disease
  -  Major surgery within 2 weeks prior to Day 1 of study or who have not yet recovered from prior surgery
  -  Use of coumadin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon)
  -  Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation < 2 weeks or who have not recovered from side effects of this therapy

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Evaluation of Patients With Bulky GIST Using Sunitinib

Summary: The primary purpose of this study is to determine if oral (mouth) delivery prior to tumor removal in patients with gastrointestinal stromal tumor (GIST) results in tumor shrinkage allowing for successful surgery. Therapy will be administered orally and the response of the tumor will be assessed using CTs or MRIs.

Detailed description: Gastrointestinal stromal tumor (GIST) is a rare cancer affecting primarily the digestive tract and sometimes abdominal cavity in adults. The most common site is the stomach followed by the duodenum and small intestine.
  Surgery is the mainstay of therapy for GIST patients whose primary tumor is felt to be resectable. Prior to the introduction of Gleevec, patients with inoperable GIST had essentially no therapeutic options. However, sunitinib trials offer options to patients who are Gleevec resistant or have intolerant GIST. Clinical benefit has been demonstrated with positive results in several sunitinib studies of varying phases.

Eligibility: Inclusion Criteria:
  -  Patients more than 19 years old with pathologically proven GIST which is bulky or marginally resectable
  -  Patients must have at least one bidimensionally measurable disease site of 5 cm or greater not previously irradiated. Bone lesions do not qualify.
  -  Patients must have an ECOG performance of greater than or equal to 2, with projected survival of at least three months.
  -  Patients must have adequate laboratory parameters:
  Hematologic: Hb >9.0; WBC >3200 and platelets >100,000/mm3; Hepatic: Bilirubin <2.0 and AST within 4 times upper limit of normal; Renal: Creatinine of less than or equal to 1.6 or eGFR greater than or equal to 50 mL/min
  -  Men and women who are of childbearing potential must practice strict birth control for the duration of the study.
  -  Women of childbearing potential must be non-lactating and non-pregnant with a negative pregnancy test within two weeks of trial registration.
  -  The patient, a witness, and attending physician will have signed an IRB-approved informed consent prior to Sunitinib administration.
  Exclusion Criteria:
  -  Known brain metastases or significant pleural effusion or ascites.
  -  Uncontrolled hypertension, diabetes, or other medical condition.
  -  Major surgery within 21 days of registration.
  -  Patients wtih organ grafts with the exception of prior high dose chemotherapy with autologous bone marrow (or stem cell) transplantation.
  -  History of seizures, central nervous system disorders, dementia, or psychosis that might preclude adequate informed consent or protocol compliance.
  -  Prior therapy for GIST.
  -  A history of HIV or hepatitis virus infection.
  -  Any recent medical condition which, in the opinion of the investigator, makes the patient unsuitable for study participation.
  -  Patients with impaired kidney function.

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Post Marketing Surveillance On The Safety And Tolerability Of Sunitinib Malate (Sutent) For Filipino Patients

Summary: The primary purpose is to monitor the safety and tolerability and effectiveness of sunitinib malate in the treatment of patients with metastatic renal cell carcinoma and gastrointestinal stromal tumor among filipino patients in usual clinical practice setting.

Detailed description: Open label

Eligibility: Inclusion Criteria:
  -  Age 18 years and above
  -  Diagnosed with metastatic renal cell carcinoma or gastrointestinal stromal tumor after imatinib treatment failure or intolerance
  Exclusion Criteria:
  -  Subjects with conditions that are contraindicated with sunitinib malate

Relevance to patient case: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

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: not relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

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: possibly relevant
Patient case: 49-year-old female with Gastrointestinal stromal tumor. Genetic variant: KIT Exon 9 (A502_Y503dup). Other conditions: None.

Clinical trial: Evaluation of Nilotinib In Patients With Advanced Gastrointestinal Stromal Tumor (GIST)

Summary: This study will assess time-to-disease progression in patients with advanced gastrointestinal stromal tumor (GIST) previously treated with imatinib ≥600 mg.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed diagnosis of GIST that is unresectable and/or metastatic
  -  Radiological confirmation of disease progression or intolerance to imatinib therapy at a any dose
  -  At least one measurable site of disease on CT scan at Visit-2
  -  WHO Performance Status of 0, 1 or 2 at Visit-2
  -  Patients must have normal organ, electrolyte, and marrow function at Visit-1 and Visit-2
  Exclusion Criteria:
  -  Prior treatment with nilotinib or any other tyrosine kinase inhibitors except imatinib.
  -  Treatment with any cytotoxic and/or investigational cytotoxic drug ≤ 4 weeks
  -  Prior or concomitant malignancies other than GIST
  -  Impaired cardiac function at Visit-1 or 2
  -  Patients with severe and/or uncontrolled concurrent medical disease
  -  Use of therapeutic coumarin derivatives
  -  Use of any medications that prolong the QT interval
  -  Use of CYP3A4 inhibitors
  -  Patients who have undergone major surgery ≤ 2 weeks prior to Visit-1 or who have not recovered from side effects of such surgery
  -  Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation < 2 weeks prior to Visit-1 or who have not recovered from side effects of such therapy
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant