araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: Study of Safety and Preliminary Efficacy for LDK378 in Japanese Patients With Genetic Alterations in Anaplastic Lymphoma Kinase (ALK)

Summary: Estimation of the Maximum tolerated dose (MTD) and/or Recommended dose (RD) of LDK378 as a single agent when administered orally to Japanese patients with tumors characterized by genetic alterations in anaplastic lymphoma kinase (ALK)


Eligibility: Inclusion Criteria:
  -  Patients with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
  -  Only patients with tumors characterized by genetic alterations in ALK. For non-small cell lung cancer (NSCLC), an ALK translocation must be detected by Fluorescent in situ hybridization (FISH) in ≥15% of tumor cells. Local site documented results on ALK alteration are acceptable for enrollment of the patients. Central confirmation of local results is not required.
  --Eastern Cooperative Oncology Group (ECOG) performance status grade ≤ 2
  -  Adequate organ function
  -  Dose-expansion part: Patients must have NSCLC that has progressed since prior therapy with alectinib. Alectinib must have been the only prior ALK inhibitor received by the patient prior to trial entry.
  Exclusion Criteria:
  -  Patients with symptomatic Central Nerve System (CNS) metastases who are neurologically unstable or require increasing doses of steroids to control their CNS disease
  -  Patients with unresolved nausea, vomiting or diarrhea > Common Terminology Criteria for Adverse Events (CTCAE) grade 1
  -  Other concurrent severe and/or uncontrolled medical conditions
  -  Patients who have been treated with chemotherapy or biologic therapy or other investigational agent < 2 weeks prior to starting the daily dosing of the study drug for compounds with a half-life ≤ 3 days, and < 4 weeks prior to starting the daily dosing of the study drug for compounds with a prolonged half-life (< 6 weeks for patients that received nitrosoureas or mitomycin-C)
  -  Unresolved toxicity greater than CTCAE grade 1 or unstable toxicity from previous anti-cancer therapy or radiotherapy (excluding neurotoxicity, alopecia, ototoxicity, lymphopenia), or incomplete recovery from previous surgery, unless agreed by Novartis and the Principal Investigator and documented
  -  Patients who have received radiotherapy to lung within 4 weeks prior to starting the daily dosing of the study drug or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites radiotherapy to a large volume (including whole brain radiotherapy) < 2 weeks prior to starting the daily dosing of the study drug, and patients who have received radiotherapy to a small volume (including stereotactic radiotherapy to the CNS) < 3 days prior to starting the study drug.
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: not relevant
Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: Clinicopathological Features of NSCLC Patients Associated With the Chromosome 2p (EML4-ALK)

Summary: Because ALK-positive lung cancer constitutes less than 5% of all lung cancers, it is critically important to select those patients who are more likely to have the ALK mutation. Clinical characteristics of patients with mutations in the target gene should also be known, so that the incidence of a given target mutation is established in a specific population. There is not incidence known in Mexican population, but it is believed it is greater.

Detailed description: Lung adenocarcinoma studies. The only inclusion criterion was the availability of tissue for biomarker studies. To identify ALK rearrangements, fluorescence in situ hybridization (FISH) studies were performed on 3 to 4 mm thick paraffin sections from NSCLCs. The commercially labeled Vysis LSI ALK Dual Color (split-apart), break-apart rearrangement probe (Abbott Molecular, Abbott Park, IL) was used to detect any rearrangement involving the ALK gene. The probe hybridizes to band 2p23, on either side of the ALK gene breakpoint. Criteria for probe signal interpretation in at least 200 interphase nuclei were as follow: 1) separated green and orange signals or single red signals identified cells with rearranged ALK; 2) overlapping of red and green signals (yellowish) indicated cells in which ALK was not rearranged.
  FISH-positive samples for ALK rearrangement were defined as having cells with a clearly separated pair of probe signals, or with >15% of cells having loss of the 5´(centromeric) probe. The higher threshold for loss is necessary because parts of probes can be lost during sectioning.
  The aim of our study is to evaluate the utility of IHC with 5A4 and RT-qPCR in the detection of ALK rearrangements in NSCLC compared with the current method of choice, FISH. Further, we report on the demographics, and clinicopathologic features of ALK-rearranged NSCLC in a Latin-American population.
  Clinical details of these patients were included in a database. Further results will be analyzed with the program SPSS17

Eligibility: Inclusion Criteria:
  -  The only inclusion criterion was the availability of tissue for biomarker studies.
  Exclusion Criteria:
  -  Disease Progression

Relevance to patient case: not relevant
Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib

Summary: The purpose of the study is to evaluate safety and efficacy of AT13387 Alone and in Combination with Crizotinib in the Treatment of Non-small Cell Lung Cancer.

Detailed description: This is a 3-part phase 1-2 study in patients with anaplastic lymphoma kinase (ALK) + or other potentially crizotinib-sensitive NSCLC who have been receiving crizotinib. Part A is a single-arm, Phase 1, open-label, dose escalation design in patients with NSCLC who have already been receiving crizotinib for at least 8 weeks and continue to tolerate therapy. Part B is a Phase 2, open-label, randomized continuation design comparing crizotinib alone versus the combination of crizotinib + AT13387 at the maximum tolerated dose established in Part A. Part C is an open-label, randomized, Phase 2, Simon's 2 stage design evaluating single agent AT13387 or combination AT13387 + crizotinib at the MTD established in Part A in patients who progressed on crizotinib at any time.

Eligibility: Inclusion Criteria:
  1. Men or women 18 years of age or older
  2. Must have Non-small Cell Lung Cancer with ALK+ mutation or other mutations or rearrangements potentially sensitive to crizotinib
  3. Measurable disease
  4. Must have been receiving or have received crizotinib
  5. Have adequate cardiac, bone marrow, liver and kidney function
  6. Must be willing and able to provide written informed consent and comply with the protocol and study procedures
  Exclusion Criteria:
  1. Prior anti-cancer treatment with any HSP90 inhibitor
  2. Have received chemotherapy, radiation therapy or other anticancer treatment other than crizotinib within 3 weeks prior to the first dose of study drug
  3. Prior malignancy other than adequately treated basal or squamous cell carcinoma of the skin, superficial bladder cancer, low-grade cervical cancer, non-metastatic prostate cancer, or have been disease-free for at least 3 years
  4. Abnormal heart function
  5. Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors
  6. Hypersensitivity of AT13387 or other components of the drug product
  7. Treatment with an investigational drug within 3 weeks prior to the first dose of study drug
  8. Severe systemic diseases or active uncontrolled infections
  9. Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus

Relevance to patient case: not relevant
Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: Phase II Study With Hiltonol and Dendritic Cells in Solid Tumors

Summary: In this phase II study, patients with solid tumors will receive treatment with hiltonol and autologous dendritic cells.

Detailed description: In this phase II study, patients with solid tumors will receive treatment with intratumoral hiltonol and two cycles of autologous dendritic cells loaded with autologous tumor and administered subcutaneously. A new cohort will explore the role of radiation therapy, looking for an abscopal effect.

Eligibility: Inclusion Criteria:
  -  Confirmed diagnosis of advanced solid tumors
  -  Measurable disease
  -  Performance status 0, 1 or 2.
  -  Adequate renal, hepatic and bone marrow function
  -  Availability of tumor tissue, for maturing dendritic cells
  Exclusion Criteria:
  -  Clinically relevant diseases or infections.
  -  concurrent participation in other clinical trial or administration or other antitumoral treatment
  -  Concurrent cancer, with the exceptions allowed by the PI.
  -  Pregnant or breast feeding women
  -  immunosuppressant treatment
  -  known uncontrolled central nervous system metastasis

Relevance to patient case: not relevant
Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: Phase I Study of LDK378 in Pediatric, Malignancies With a Genetic Alteration in Anaplastic Lymphoma Kinase (ALK)

Summary: The purpose of this study is to estimate the maximum tolerated dose and/or recommended dose for expansion of LDK378 as a single agent, assess safety, tolerability and anti-tumor activity and characterize single and multiple-dose pharmacokinetics when administered orally to pediatric patients with ALK-activated tumors, with and without food.

Detailed description: LDK378 is a novel inhibitor of ALK that is active in a broad range of ALK-activated tumor models, including models driven by mutated versions of ALK known to be resistant to crizotinib, and by ALK gene amplification.
  The primary purpose of this study is to determine the maximum tolerated dose and/or recommended dose for expansion in pediatric patients, and to delineate a clinical dose to be used in any future pediatric studies, with and without food. This study will also assess the safety, tolerability, PK and preliminary evidence of antitumor activity of LDK378 in pediatric patients with neuroblastoma, and other ALK-activated tumors.

Eligibility: Inclusion Criteria:
  -  Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
  -  Age ≥ 12 months and < 18 years
  -  The tumor must carry a genetic alteration of ALK
  -  Patients must have evaluable or measurable disease
  Exclusion criteria:
  -  Symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy (such as radiotherapy, surgery or intrathecal chemotherapy) to control their CNS disease
  -  Clinically significant, uncontrolled heart disease
  -  Inadequate end organ function as defined by specified laboratory values
  -  Use of medications that are known to be strong inhibitors or inducers of CYP3A4/5 that cannot be discontinued at least 1 week prior to start of treatment with LDK378 and for the duration of the study
  -  Use of medications that are mainly metabolized by CYP3A4/5 or CYP2C9 that cannot be discontinued at least 1 week prior to start of treatment with LDK378 and for the duration of the study.
  -  History of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis
  -  History of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
  -  Medications with a known risk of prolongation of QT interval
  Other protocol defined inclusion and exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer

Summary: The primary purpose of the study was to compare the antitumor activity of LDK378 versus reference chemotherapy. Patients in the chemotherapy arm were allowed to cross-over to LDK378 after confirmed progressive disease (PD).


Eligibility: Inclusion Criteria:
  1. Patient has a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that is Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test will be performed at Novartis designated central laboratories.
  2. Patient has newly diagnosed stage IIIB (who are not a candidate for definitive multimodality therapy) or stage IV NSCLC or relapsed locally advanced or metastatic NSCLC not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other targeted therapies, either experimental or not), with exception of neo-adjuvant or adjuvant therapy
  3. Patient has at least one measurable lesion as defined by RECIST 1.1.
  Exclusion Criteria:
  1. Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
  2. Patient with a history of severe hypersensitivity reaction to platinum containing drugs, pemetrexed or any known excipients of these drugs.
  3. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.

Relevance to patient case: not relevant
Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib

Summary: The primary purpose of the study was to compare the antitumor activity of LDK378 vs. chemotherapy in patients previously treated with chemotherapy (platinum doublet) and crizotinib.


Eligibility: Inclusion Criteria:
  1. Patient has a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as assessed by the FDA approved Abbott FISH Test.
  2. Patient has stage IIIB or IV diagnosis and must have received one or two prior regimens (including platinum- doublet) of cytotoxic chemotherapy for the treatment of locally advanced or metastatic NSCLC.
  3. Patient has at least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation
  4. Patients must have received previous treatment with crizotinib for the treatment of locally advanced or metastatic NSCLC.
  Exclusion Criteria:
  1. Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
  2. Patient with a history of severe hypersensitivity reaction to pemetrexed or docetaxel or any known excipients of these drugs.
  3. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.

Relevance to patient case: not relevant
Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: A Study of Alectinib (CH5424802/RO5424802) in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (NSCLC)

Summary: This non-randomized, open-label, multicenter study will evaluate the safety and efficacy of alectinib in participants with ALK-rearranged non-small cell lung cancer who failed crizotinib treatment. In Phase I, cohorts of participants will receive escalating doses of alectinib orally twice daily. In Phase II, patients who failed crizotinib treatment will receive the recommended phase II dose.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed, locally advanced, not amenable to curative therapy, or metastatic NSCLC
  -  ALK-rearrangement confirmed by the Food and Drug Administration (FDA) approved test
  -  NSCLC that has failed crizotinib treatment
  -  Measurable disease as defined by RECIST v1.1
  -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 2
  -  Adequate hematologic, hepatic and renal function
  Exclusion Criteria:
  -  Prior therapy with ALK inhibitor other than crizotinib
  -  Brain or leptomeningeal metastases that are symptomatic and/or requiring treatment
  -  History of serious cardiac dysfunction
  -  History of or current active infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
  -  Clinically significant gastrointestinal abnormality that would affect absorption of the drug
  -  Pregnant or lactating women

Relevance to patient case: not relevant
Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: Analysis of Plasma Tumor DNA in Lung Cancer Patients

Summary: The presence of genetic alterations in the tyrosine kinase domain of the oncogene (eg. EGFR and ALK) is associated with the clinical response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancers. Therefore, the detection of altered genetic alterations is useful for predicting the treatment response for TKIs in non-small cell lung cancer patients. However, good quality tumor tissues are available only in <50% of patients with inoperable lung cancer for mutation analysis. In this study, the investigators will detect and quantify the genetic alterations in plasma. the investigators will investigate if the serial measurement of cancer-derived genetic alterations in plasma can provide a means for monitoring disease progression, as well as treatment response. In addition the investigators will analysis the resistant mechanism of TKIs and chemotherapy with plasma tumor DNA.


Eligibility: Inclusion Criteria:
  -  Have a histologically or cytologically confirmed diagnosis of non-small cell lung cancer
  -  Have molecular evidence of genetic alterations in tumor sample (eg. EGFR mutations, ALK fusions)
  -  Patients must have given written informed consent
  Exclusion Criteria:
  -  Patients who refuse the blood samplings

Relevance to patient case: not relevant
Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: A Phase 1b Study Of Axitinib In Combination With Crizotinib In Patients With Advanced Solid Tumors

Summary: Despite the success of anti-angiogenic therapy in multiple treatment settings, a fraction of patients are refractory to vascular endothelial growth factor (VEGF) inhibitor treatment, while the majority of patients will eventually develop evasive resistance. It is proposed that mesenchymal-epithelial transition factor (c-MET) and its ligand hepatocyte growth factor (HGF or scatter factor) contribute to VEGF inhibitor resistance, such that combining a c-MET inhibitor with a VEGF inhibitor will provide additional clinical activity compared to VEGF inhibitor alone. This hypothesis will be tested using the cMET/ALK inhibitor, crizotinib, in combination with the VEGF inhibitor, axitinib.Since this will be the first study of axitinib given in combination with crizotinib, the study will primarily assess the safety and tolerability of the combination regimen.


Eligibility: Inclusion Criteria:
  -  Diagnosis - Dose Escalation Phase: Histologically or cytologically confirmed diagnosis of advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available.
  -  Diagnosis - Dose Expansion Phase: Histologically or cytologically confirmed advanced RCC with a component of clear cell subtype
  -  Dose Expansion Phase: at least one measureable lesion as defined by RECIST [Response Evaluation Criterion in Solid Tumors] version 1.1.
  -  ECOG [Eastern Cooperative Oncology Group] Performance Status 0 or 1.
  Exclusion Criteria:
  -  Major surgery <4 weeks or radiation therapy <2 weeks of patient registration.
  -  History of or known active seizure disorder, brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
  -  Dose Expansion Phase only: diagnosis of any other malignancy within 2 years prior to registration.

Relevance to patient case: possibly relevant
Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

Clinical trial: NanOss Bioactive With Autograft and Bone Marrow Aspirate in the Posterolateral Spine

Summary: The purpose of this study is to assess lumbar fusion using nanOss Bioactive bone void filler


Eligibility: Inclusion Criteria:
  1. Is at least 21 years of age and skeletally mature.
  2. Must have cervical disc disease (defined as neck pain of discogenic origin with degeneration of the disc confirmed by history and radiographic studies) at one level in the cervical spine between C3 to T1.
  3. Must have completed a minimum of six weeks of unsuccessful conservative, non-operative care or has the presence of progressive symptoms or signs of nerve root/spinal cord compression in the face of conservative treatment.
  4. Has pre-operative objective evidence of primary diagnosis confirmed by appropriate imaging studies (Anteroposterior/Lateral/Flexion/Extension X-rays & a recent MRI).
  5. Is willing and able to comply with all clinical investigation visits and procedures including screening treatment procedures, post-operative management, the follow-up schedule and completion of forms or questionnaires.
  6. Is able to understand and sign the patient information sheet/informed consent form.
  Exclusion Criteria:
  1. Requires fusion at more than one level.
  2. Has had prior fusion at the level to be treated.
  3. Has a metabolic or systemic bone disorder.
  4. Has a disease that significantly inhibits bone healing (i.e., severe osteoporosis, osteomalacia, Paget's disease).
  5. Has a systemic or local infection (active or latent).
  6. Has acute or chronic infections in the surgical area (i.e., soft tissue infections; inflammatory, bacterial bone disorders, osteomyelitis).
  7. Chronic use of steroids, other than episodic use or inhaled corticosteroids.
  8. Has any significant general illness (i.e., HIV, active metastatic cancer of any type, uncontrolled diabetes Type I, dialysis dependent renal failure, symptomatic liver disease).
  9. Has a mental or physical condition that would limit the ability to comply with study requirements or would preclude accurate evaluation.
  10. Is immunocompromised or being treated with immunosuppressive agents (including chemotherapy or radiation treatment).
  11. Has documented allergies to hydroxyapatite or porcine collagen, PEEK, titanium, titanium alloy or tantalum.
  12. Is currently pregnant, or interested in becoming pregnant during the clinical investigation follow-up.
  13. Is a smoker.
  14. Is non-English speaking.
  15. Requires the use of a bone-growth stimulator.
  16. Is a prisoner.
  17. Is currently involved in another drug or device clinical investigation that may confound the clinical trial investigation

Relevance to patient case: not relevant