araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

Clinical trial: A Clinical Study Testing The Safety and Efficacy of CH5424802/RO5424802 in Patients With ALK Positive Non-Small Cell Lung Cancer

Summary: CH5424802 is a newly invented, selective oral ALK inhibitor. In the Phase I portion, the goal is to determine the following: dose limiting toxicity, the maximum tolerated dose, pharmacokinetic (PK) parameters, and the recommended dose.


Eligibility: Inclusion Criteria:
  -  ECOG performance status =< 2
  -  Confirmed of ALK-positive NSCLC by FDA approved kit
  -  NSCLC that has failed crizotinib treatment for Phase I
  -  Measurable disease defined by RECIST 1.1
  -  Adequate hematologic, hepatic, renal function
  Exclusion Criteria:
  -  Prior therapy with an ALK inhibitor other than crizotinib
  -  Brain metastases, which are symptomatic and/or requiring treatment
  -  History of serious cardiac dysfunction
  -  Clinically significant gastrointestinal abnormality that would affect the absorption of drug
  -  Pregnant or a lactating woman

Relevance to patient case: not relevant
Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

Clinical trial: Studying Chromosomes in Samples From Younger Patients With Neuroblastoma

Summary: This research studies chromosomes in samples from younger patients with neuroblastoma. Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

Detailed description: OBJECTIVES:
  I. Determine the impact on overall survival of patients with non-MYCN neuroblastoma below 18 months of age as compared to neuroblastoma patients above 18 months of age.
  OUTLINE:
  Archived DNA samples are analyzed for segmental chromosome aberrations by multiplex ligation-dependent probe amplification (MLPA), a polymerase chain reaction (PCR)-based technique. The following genomic regions are being studied: 1p, 1q, 3p, 4p, 7q, 9p, 11q, and 17q, as are the copy numbers of MYCN, NAG, DDX1, and ALK genes.

Eligibility: Inclusion Criteria:
  -  Samples from neuroblastoma patients who, according to risk stratification, did not receive cytotoxic treatment and did never receive chemotherapy and are in complete response (CR) OR patients who, according to risk stratification, did not receive cytotoxic treatment initially, but had a localized or a systemic (stage Ms or M) relapse with or without following chemotherapy
  -  Low-risk Children Oncology Group (COG) designation: no initial cytotoxic treatment, any stage, any age, any outcome
  -  DNA from untreated neuroblastoma tumor samples (from patients in the age group below and from patients in the age group above 1.5 years of age) available from the COG, Europe, Israel, and Japan
  -  No MYCN amplification
  -  No Schwann cell stroma-rich tumors
  -  No tumor cell content below 60%
  -  No DOT
  -  No patients diagnosed before 1997 and after 2005
  -  No lack of follow-up data
  -  See Disease Characteristics
  -  No initial cytotoxic treatment

Relevance to patient case: not relevant
Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

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: 4-year-old female with neuroblastoma; genetic feature: ALK

Clinical trial: Exploring the Possibility to Use Glycosyltransferase as a Prognosis Marker of Neuroblastoma

Summary: Well-regulated glycosylation is essential for the normal development of the nervous system. Altered expression of glycosyltransferases with resulting dysregulated glycosylation of neuroblastic cells might lead to the development of NB. The β1,4-N-acetylgalactosaminyltransferase III (B4GALNT3) exhibits GalNAc transferase activity to form the GalNAcβ1,4GlcNAc (LacdiNAc or LDN) structure. The Drosophila B4GALNTA, homolog of human B4GALNT3, has been suggested to regulate the neuronal development. By immunohistochemical studies, we demonstrated that the expression of B4GALNT3 correlated well with histological grade of differentiation in NB tumor samples. Since well differentiated tumors usually carry a better prognosis, we thus speculate that expression of B4GALNT3 in tumor tissues can a favorable prognostic factor of NB.
  To explore the role of B4GALNT3 in the prognosis of NB, we propose the following project with two specific aims:
  Aim Ⅰ: Establishing the significance of B4GALNT3 in the prognosis of NB: We plan to collect 90 NB tumor samples, and evaluate the RNA and protein expression levels by Q-PCR, Western blot, and immunohistochemistry in the tumor samples. The results will be compared with the other clinicopathological and biological factors of NB. Also the expression levels of B4GALNT3 in tumor tissues will be correlated to the patients' outcome to clarify whether B4GALNT3 could be a prognosis marker of NB.
  Aim II: Clarifying the effects of B4GALNT3 on NB cell behavior in vitro and in vivo. For further strengthening the prognostic role of B4GALNT3 in NB, NB cell phenotype and behavior changes after overexpression or knock-down of B4GALNT3 are evaluated by in vitro assays as well as by a nude mice xenograft model.
  In summary, if our project can establish the role of B4GALNT3 expression in NB, we may further subclassify the NB patients, and give the NB patients more appropriate therapies to improve patients' outcome. Furthermore, B4GALNT3 could potentially serves as a therapeutic target in the future.


Eligibility: Inclusion Criteria:
  -  Neuroblastoma patients with complete follow-up and sufficient samples for study
  Exclusion Criteria:
  -  Neuroblastoma patients without complete follow-up or sufficient samples for study

Relevance to patient case: not relevant
Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

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: possibly relevant
Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

Clinical trial: Combination Therapy of Antibody Hu3F8 With Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) in Patients With Relapsed/Refractory High-Risk Neuroblastoma

Summary: The purpose of this study is to find out if an antibody called Humanized 3F8 (Hu3F8) combined with granulocyte- macrophage colony stimulating factor (GM-CSF) is safe for treating neuroblastoma.


Eligibility: Inclusion Criteria:
  -  Diagnosis of NB as defined by a) histopathology (confirmed by the MSKCC Department of Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine levels.
  -  Patients must have high-risk NB (including MYCNamplified stage 2/3/4/4S of any age and MYCN-nonamplified stage 4 in patients greater than 18 months of age) AND:
  -  Phase I: Patients must have refractory or relapsed NB, resistant to standard therapy*.
  *For NB, standard therapy includes intensive induction chemotherapy, followed by a variety of consolidation or salvage therapies, depending on response.
  -  Phase II: Patients must have primary or secondary refractory disease in BM, defined as morphologic evidence of NB in BM and/or abnormal 123I-MIBG uptake in osteomedullary sites, OR patients are in ≥2nd CR/VGPR
  -  Patients must be older than 1 year of age.
  -  Prior treatment with murine and humanized 3F8 is allowed. Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have HAHA antibody titer ≤1300 Elisa units/ml. Human anti-mouse antibody positivity is allowed.
  -  White blood cell count ≥1000/ul (phase I only)
  -  Absolute neutrophil count ≥500/ul (phase I only)
  -  Absolute lymphocyte count ≥500/ul (phase I only)
  -  Platelet count ≥25,000/ul (phase I only)
  -  No chemotherapy or immunotherapy for a minimum of three weeks prior to start of hu3F8
  -  Women of child-bearing potential must be willing to practice an effective method of birth control while on treatment
  -  Signed informed consent indicating awareness of the investigational nature of this program.
  Exclusion Criteria:
  -  Existing major organ dysfunction > grade 2, with the exception of hearing loss and hematologic toxicity (defined as suppression of all subtypes of WBCs, RBCs, and platelets).
  -  Active life-threatening infection.
  -  Pregnant women or women who are breast-feeding.
  -  Inability to comply with protocol requirements, including PK studies and genetic studies (phase I only)
  -  History of allergy to mouse proteins.
  -  Human anti-hu3F8 antibody (HAHA) titer >1300 Elisa units/ml.
  -  History of allergy to GM-CSF

Relevance to patient case: not relevant
Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

Clinical trial: 131I-MIBG Alone VS. 131I-MIBG With Vincristine and Irinotecan VS131I-MIBG With Vorinistat

Summary: This study will compare three treatment regimens containing metaiodobenzylguanidine (MIBG) and compare their effects on tumor response and associated side effects, to determine if one therapy is better than the other for people diagnosed with relapsed or persistent neuroblastoma.


Eligibility: Inclusion Criteria:
  -  Patients must be > 24 months and < 30 years of age when registered on study.
  -  Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to frontline therapy frontline therapy with > 3 residual lesions on end-induction MIBG scan.
  -  Patients must have evidence of MIBG uptake into tumor at ≥ one site within 4 weeks prior to entry on study and subsequent to any intervening therapy.
  -  Patients must have adequate heart, kidney, liver and bone marrow function. Patients who have bone marrow disease must still have adequate bone marrow function to enter the study.
  -  Patients must have a dose of unpurged peripheral blood stem cells is 2.0 x 106 viable CD34+ cells/kg available.
  Exclusion Criteria:
  -  They have had previous I-131 MIBG therapy
  -  They have other medical problems that could get much worse with this treatment.
  -  They are pregnant or breast feeding.
  -  They have a history of a venous or arterial thrombosis that was not associated to a central line.
  -  They have active infections such as hepatitis or fungal infections.
  -  They have active diarhhea.
  -  They have had an allogeneic stem cell transplant (received stem cell from someone else)
  -  They can't cooperate with the special precautions that are needed for this trial.

Relevance to patient case: not relevant
Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

Clinical trial: Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations.

Summary: Entrectinib (RXDX-101) is an orally available inhibitor of the tyrosine kinases TrkA (coded by the gene NTRK1), TrkB (coded by the gene NTRK2), TrkC (coded by the gene NTRK3), ROS1 (coded by the gene ROS1), and ALK (coded by the gene ALK). Molecular alterations to one or more of these targets are present in several different tumor types, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), prostate cancer, papillary thyroid cancer, pancreatic cancer, and neuroblastoma. Patients with locally advanced or metastatic cancer with a detectable molecular alteration in targets of interest may be eligible for enrollment.
  Phase 1 will assess safety and tolerability of entrectinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and efficacy will be assessed in the dose expansion portion of the study.


Eligibility: Key Inclusion Criteria:
  -  Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors that have a NTRK1, NTRK2, NTRK3, ROS1, or ALK molecular alteration.
  -  Measurable disease according to RECIST version 1.1.
  -  Prior cancer therapy is allowed, including crizotinib, ceritinib, and investigational drugs.
  -  Prior radiotherapy is allowed
  -  Patients with controlled asymptomatic central nervous system involvement are allowed.
  -  Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
  -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
  -  Adult patients age 18 years or older.
  -  Life expectancy of at least 3 months.
  Key Exclusion Criteria:
  -  Current participation in another therapeutic clinical trial.
  -  Prior treatment with entrectinib.
  -  History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds).
  -  History of additional risk factors for torsade de pointes (e.g., family history of long QT syndrome).
  -  Known active infections (bacterial, fungal, viral including HIV positivity).
  -  Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
  -  Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis.
  -  Peripheral neuropathy ≥ Grade 2.

Relevance to patient case: not relevant
Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

Clinical trial: Project HERA (Health, Education, and Relationship-building for Adolescents- Moms and Tots)

Summary: Specific Aims:
  1. The primary aims of this study are to conduct formative interviews with teen mothers to inform a targeted adaptation of empirically based weight management and parent training programs for teen mothers for their preschoolers.
  2. To conduct a small pilot and post-pilot focus group of the feasibility and acceptability of recruitment and retention methods & the intervention.
  Study Hypotheses:
  Given the small sample size and fact that this is a pilot study, focus will be on estimating effect sizes rather than statistical hypothesis testing. However, the investigators exploratory hypotheses are as follows:
  1. (a) The adapted intervention will be more feasible compared to the wellness control condition, with a participant retention rate of ≥80% and an average adherence (attendance at weekly treatment sessions; homework completion 5 weekdays weekly) is ≥ 75%; (b) The adapted intervention will be more acceptable compared to the wellness control condition, based on the Consumer Satisfaction Scale and Therapy Assessment Inventory with ≥90% of the participants responding to the item, "In general how satisfied were you with the intervention?" by choosing "unsatisfied" to "very satisfied."
  2. (a) The adapted intervention will result in greater improvements in child behavior and parent-child connectedness compared to the control condition; (b) the adapted intervention versus wellness control condition will result in greater increases in child and teen mother individual as well as joint physical activity and physically active play and greater reductions in individual and joint teen mother and child sedentary behavior (television viewing) from baseline to post-intervention; (c) the greater teen mother and child fruit and vegetable consumption; and reduced child juice and sugar-sweetened beverage consumption from baseline to post-intervention; (d) the adapted intervention versus wellness control condition will result in smaller increases in child BMI percentile and teen mother BMI from baseline to post-intervention; (e) participants who attend higher numbers of intervention sessions will show greater improvements in target outcomes (child behavior, parent-child connectedness, and teen mother and child physical activity, sedentary behavior and BMI); with participants receiving the adapted intervention versus wellness control showing the greatest dose-based improvements.


Eligibility: Inclusion Criteria:
  -  Must be teen moms
  -  Be between 16 and 20 years of age
  Exclusion Criteria:
  -  Does not have a child between the ages of 6 months and 5 years

Relevance to patient case: not relevant
Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

Clinical trial: Study to Evaluate Real-world Pharmacoeconomics of Crizotinib in NSCLC Patients

Summary: This is a phase IV multicenter trial to evaluate the pharmacoeconomic (PE) impact of crizotinib and its companion diagnostic test used in a real-life setting in advanced ALK-positive non-small cell lung cancer (NSCLC) patients.
  NSCLC represent 80% of all new cases of lung cancer. One molecular subtype of NSCLC is the ALK-positive subtype. The anaplastic lymphoma kinase (ALK) is a transmembrane receptor tyrosine kinase. Activation of ALK occurs through the formation of gene fusions and in NSCLC, the gene fusion partner for ALK is primarily EML4. The resulting fusion protein is capable of activating the ALK kinase domain, leading to cell growth. The estimated prevalence for ALK rearrangements in NSCLC is 3-5%, and is more commonly found amongst patients with adenocarcinoma histology, in never smokers and in those who are known to be wild type for EGFR and KRAS.
  Crizotinib is a potent inhibitor of ALK and is approved for the treatment of advanced ALK+ NSCLC patients. This is an example of personalized medicine, where patients are selected for treatment based upon a molecular assay, and are provided a specific therapy (crizotinib) for their disease. The pharmacoeconomic impact of using genetic information in early treatment decisions in NSCLC has not been determined.
  The study will enable real-life Heath Economics and Outcome Research (HEOR).
  Approximately 90 patients will be recruited. Patients will be asked to complete quality-of-life questionnaires at regular intervals in a real-life setting of treatment with crizotinib.


Eligibility: Inclusion Criteria:
  -  Patients with histologically confirmed locally advanced or metastatic NSCLC
  -  Presence of the ALK-fusion oncogene (ALK+) as determined using a validated testing platform
  -  Planned first or second-line treatment with crizotinib
  -  Signed and dated IRB-approved informed consent document
  -  Ability to read and understand English or French
  -  18 years of age or older

Relevance to patient case: not relevant