araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: Extension to the Study of Efficacy of CDZ173 in Patients With APDS/PASLI

Summary: This study is designed to provide long-term CDZ173 treatment, a selective PI3Kδ inhibitor, to the patients with genetically activated PI3Kδ, i.e., patients with APDS/PASLI who participated in the CCDZ173X2201 study or who were treated previously with PI3Kδ inhibitors other than CDZ173. The study is open-label designed to establish the long-term safety, tolerability, efficay and pharmacokinetics of CDZ173 in the target population.


Eligibility: Inclusion Criteria:
  -  Written informed consent must be obtained before any assessment is performed.
  -  Paients must have participated in the study CCDZ173X2201 or were treated previously with PI3Kδ inhibitors other than CDZ173.
  -  Patients who are deemed by the Investigator to benefit from PI3Kδ inhibitor therapy.
  -  Patients or their legal representatives (for patients under the age of 18 years) must be able to communicate well with the Investigator, to understand and comply with the requirements of the study.
  -  Documented APDS/PASLI-associated genetic PI3K delta mutation.
  Exclusion Criteria:
  - Any medically significant disease or condition that is unrelated to APDS/PASLI
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: not relevant
Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: Plasma Triglyceride Lipolysis in Multifactorial Chylomicronemia

Summary: Purpose: The mechanism of most of the multifactorial chylomicronemia (MCM) remains elusive. In order to decipher the mechanisms involved in the occurrence of this disease, plasma TG lipolysis characteristics will be monitored for 60 minutes after heparin injection instead of the 10 minutes gold standard, in a large group of genotyped MCM patients.

Detailed description: Purpose: The mechanism of most of the multifactorial chylomicronemia (MCM) remains elusive. In order to decipher the mechanisms involved in the occurrence of this disease, plasma TG lipolysis characteristics will be monitored for 60 minutes after heparin injection instead of the 10 minutes gold standard, in a large group of genotyped MCM patients.
  Method: LPL, APOC2, APOA5, GPIHB1and APOE genotypes will be determined for each patient. Basal lipid profiles including Apo B, CII, CIII, and lipoprotein lipase (LPL) concentration will be measured in 62 MCM patients, in addition to LPL activity (PHLA) T0, T10 T30 T60 minutes, Assessment of TG chylomicron decrease Study of lipoprotein remodelling by agarose gel electrophoresis.
  Hypothesis To confirm the preliminary finding of high LPL activity in multifactorial chylomicronemia To explore the interest of a longer assessment of LPL activity following heparin injection. To establish if specific phenotypes could be identified among MCM patient supporting the hypothesis of different mechanisms involved (ie overproduction or defect in hepatic clearance)

Eligibility: Inclusion Criteria:
  -  patient with a documented history of MCM (Plasma TG concentration (TG) > 15 mmol/l or familial history of hypertriglyceridemia with TG >10 mmol/l)
  -  no contraindication for a single heparin injection for ex vivo LPL activity assessment
  Exclusion Criteria:
  -  patients carriers of homozygous or compound heterozygous mutations on LPL, GPIHBP1, APOA5, APOC2 or APOE genes

Relevance to patient case: not relevant
Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: Study on Aspirin Versus Placebo in Resected Colon Cancer With PI3K Mutation Stage III or II High Risk

Summary: Four retrospective studies were recently published on efficacy of aspirin in patients with surgically resected colon cancer. Two of these studies strongly suggested that aspirin used in low doses (100 mg/d) after surgical resection of colorectal cancer with PI3K mutation could act as a targeted therapy with a major protective effect on the risk of recurrence. The other two studies did not confirm the benefit of aspirin in this situation. These four retrospective studies provide an insufficient level of evidence to demonstrate the benefit of low-dose aspirin as adjuvant to surgery for colorectal cancer. Therefore, it is necessary as recommended in the conclusion of these studies and meta-analyses to perform a randomised prospective study to validate these data.


Eligibility: Inclusion Criteria:
  -  Age ≥ 18 years
  -  Colonic adenocarcinoma stage III
  -  Colonic adenocarcinoma stage II high risk MSS:
  -  T4bN0 or T4aN0 tumour penetrating the surface of the visceral peritoneum
  -  or less than 12 nodes evaluated;
  -  or with at least two of the following criteria:lymphatic involvement, perineural invasion, venous invasion
  -  or diagnosis of bowel obstruction or perforation; or poor differentiated tumour.
  -  PI3K mutation, exon 9 or 20 (tumour)
  -  Resection R0
  -  WHO performance status 0-2
  -  Chest and abdominal CT scan ≤ 8 weeks
  -  Life expectancy ≥ 3 years
  -  Written consent signed
  Exclusion Criteria:
  -  Anticoagulant and/or Antiaggregating treatment including clopidogrel
  -  Regular aspirin use (> 3 doses per week during more than 3 months the last year)
  -  Contraindication to Aspirin : Allergy to aspirin, Active or antecedent peptic ulcer
  -  Severe renal or hepatic insufficiency
  -  Pregnancy or nursing ongoing
  -  Rectal cancer
  -  Hereditary forms (i.e. lynch syndrome patients)
  -  Follow-up of the patient not feasible

Relevance to patient case: definitely relevant
Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: K-BASKET, TAS-117, PI3K/AKT Gene Aberration

Summary: The phosphatidylinositol 3-kinase (PI3K)-v-akt murine thymoma viral oncogene homolog (AKT)-mammalian target of rapamycin (mTOR) signaling pathway is one of the most frequently aberrantly regulated pathways in human tumors. TAS-117 is a highly potent and selective oral allosteric AKT inhibitor. It has high affinity for AKT1, 2, and 3 and shows potent anti-proliferative activity against multiple tumor cell lines in vivo. Therefore, we propose to conduct a phase II trial of TAS-117, potent and selective AKT inhibitor, in patients with advanced solid tumor with PI3K/AKT genetic aberrancy by NGS focusing panel in part of K-BASKET trial.


Eligibility: Inclusion Criteria:
  1. Histologically or cytologically confirmed recurrent or advanced solid cancers with PI3K/ATK aberration
  2. Progressive disease who failed to previous standard treatment.
  3. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 criteria
  4. Eastern Cooperative Oncology Group performance status 0 or 1
  5. Able to take medications orally
  6. Adequate organ function
  7. A life expectancy of at least 60 days
  Exclusion Criteria:
  1. Previous treatment with anti-PI3K or AKT directed therapies
  2. Known hypersensitivity to any drugs similar to TAS-117 in structure or class.
  3. History or current evidence of type 1 or type 2 diabetes mellitus that requires insulin and/or oral antidiabetic therapy.
  4. Current evidence of retinopathy that requires ophthalmological therapy.
  5. History or current evidence of cardiac arrhythmia and/or conduction abnormality.
  6. Treatment with any of the following within the specified time frame prior to study drug administration:
  -  Major surgery within prior 4 weeks
  -  Radiation therapy for extended field within 4 weeks prior to study drug administration or limited field radiation therapy within 2 weeks prior to study drug administration.
  -  Any anticancer treatment within 3 weeks prior to study drug administration (mitomycin within prior 5 weeks).
  7. A serious illness or medical condition(s)
  8. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding alopecia, skin pigmentation and anemia).
  9. Patients with the risk of hypokalemia
  10. Receiving oral steroid medication.
  11. Pregnant or lactating female

Relevance to patient case: possibly relevant
Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: Nivolumab, Ipilimumab and COX2-inhibition in Early Stage Colon Cancer: an Unbiased Approach for Signals of Sensitivity

Summary: In this exploratory study, patients with stage 1-3 adenocarcinoma of the colon with no signs of distant metastases will be treated with short-term immunotherapy + COX2-inhibitors. This treatment will be given during the window period until surgical resection of the tumor. The duration of treatment will be approximately 6 weeks.

Detailed description: In this single-center, open-label, exploratory study, the investigators will enroll 60 patients within two years, including 30 patients with MSS tumors and 30 patients with MSI tumors. Patients with MSS tumors will be randomized to either group 1 or 2. Patients with MSI tumors will all be allocated to group 1.
  Patients in group 1 will be treated with a single dose of ipilimumab 1mg/kg on day 1 and two cycles of nivolumab 3mg/kg on day 1 and 15, respectively.
  Patients in group 2 will be treated with a single dose of ipilimumab 1mg/kg on day 1, two cycles of nivolumab 3mg/kg one day 1 and 15 and celecoxib daily until the day before surgery.

Eligibility: Inclusion criteria:
  -  Signed written informed consent
  -  Patients at least 18 years of age
  -  Stage 1-3 adenocarcinoma of the colon
  Exclusion criteria:
  -  No signs of distant metastases
  -  No signs of obstruction or macroscopic bleeding or suspicion of perforation
  -  Colonoscopy must be performed after registration to obtain study-specific biopsies. If biopsies are not possible, patients cannot be included in the study
  -  WHO performance status of 0 or 1
  -  No previous treatment with immune checkpoint inhibitors targeting CTLA-4, PD-1 or PD-L1
  -  For patients with MSS tumors: no current use of NSAIDs or COX2-inhibitors at registration and no active peptic ulcer, gastrointestinal bleeding, unstable ischemic heart disease of thrombus etiology or significant established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease
  -  No radiotherapy prior to or planned post-surgery radiotherapy
  -  No history of allergy to study drug components, severe hypersensitivity reaction to any monoclonal antibody, allergy or severe hypersensitivity to NSAIDs or COX2-I (MSS tumors)
  -  No intercurrent illnesses, including but not limited to infections, unstable angina pectoris
  -  No positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection and no history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  -  No autoimmune disease
  -  No conditions requiring systemic treatment with either corticosteroids (10 mg daily prednisone or more and equivalents) or other immunosuppressive medications within 14 days of study drug administration
  -  No live vaccines in the 4 weeks prior to inclusion

Relevance to patient case: not relevant
Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: Phase II Trial of Vistusertib（AZD2014） Single Agent in TSC1or 2 Null or TSC 1/2 Mutation Solid Cancer Patients Refractory to Standard Chemotherapy

Summary: Patients with TSC1/2 mutated refractory solid cancer will receive vistusertib(AZD2014) monotherapy. Study-arm is composed of 27 patients. Vistusertib(AZD2014) 50mg BD continuous schedule of a 28 day cycle as a monotherapy

Detailed description: Patients with TSC1/2 mutated refractory solid cancer will receive vistusertib(AZD2014) monotherapy. Study-arm is composed of 27 patients.
  Vistusertib(AZD2014) 50mg BD continuous schedule of a 28 day cycle as a monotherapy Tumour evaluation using RECIST 1.1 will be conducted at screening (within 28 days prior to first dose) and every 8 weeks relative to the date of first dose, up to week 40, then every 16 weeks until objective disease progression (within a window of +/- 7 days of the scheduled date).
  Study treatment will be continued until objective disease progression (unless other criteria for treatment discontinuation are met). Patients may continue vistusertib(AZD2014) beyond progression (according to RECIST 1.1), at the discretion of the investigator if they are clinically benefiting from the treatment and they do not meet any other discontinuation criteria.
  If a patient discontinues study treatment prior to disease progression, they should continue to be assessed using RECIST 1.1 until disease progression and then followed up for survival.

Eligibility: Inclusion Criteria:
  1. Advanced solid cancers (including histologically or cytologically documented gastric cancer, colorectal cancer, hepatoma, biliary tract cancers, pancreatic cancer and rare cancers.) that has progressed after standard chemotherapy.
  2. Provision of tumor sample (from either a resection or biopsy)
  3. Patients with TSC1or 2 null or TSC 1/2 mutation through IHC.
  4. Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below:
  -  Haemoglobin ≥9.0 g/dL (transfusion allowed)
  -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  -  White blood cells (WBC) > 3 x 109/L
  -  Platelet count ≥100 x 109/L (transfusion allowed)
  -  Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
  -  AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
  -  Serum creatinine ≤1.5 x institutional ULN
  Exclusion Criteria:
  1. Any previous treatment with PIK3CA, AKT or mTOR inhibitor or agents with mixed PI3K / mTOR activity.
  2. For vistusertib(AZD2014):
  Exposure to potent or moderate inhibitors or inducers of CYP3A4/5 if taken within the stated washout periods before the first dose of study treatment With the exception of alopecia, any ongoing toxicities (>CTCAE grade 1) caused by previous cancer therapy.
  3. Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.

Relevance to patient case: not relevant
Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: Phase II Trial of AZD2014 in RICTOR Amplified Solid Cancer Patients Refractory to Standard Chemotherapy

Summary: Patients with RICTOR amplified refractory solid cancer will receive vistusertib(AZD2014). Study-arm is composed of 27 patients.
  Vistusertib(AZD2014) 50mg BD continuous schedule of a 28 day cycle Tumour evaluation using RECIST 1.1 will be conducted at screening (within 28 days prior to first dose) and every 8 weeks relative to the date of first dose, up to week 40, then every 16 weeks until objective disease progression (within a window of +/- 7 days of the scheduled date).

Detailed description: Patients with RICTOR amplified refractory solid cancer will receive vistusertib(AZD2014). Study-arm is composed of 27 patients.
  Vistusertib(AZD2014) 50mg BD continuous schedule of a 28 day cycle Tumour evaluation using RECIST 1.1 will be conducted at screening (within 28 days prior to first dose) and every 8 weeks relative to the date of first dose, up to week 40, then every 16 weeks until objective disease progression (within a window of +/- 7 days of the scheduled date).
  Study treatment will be continued until objective disease progression (unless other criteria for treatment discontinuation are met). Patients may continue vistusertib(AZD2014) beyond progression (according to RECIST 1.1), at the discretion of the investigator if they are clinically benefiting from the treatment and they do not meet any other discontinuation criteria.
  If a patient discontinues study treatment prior to disease progression, they should continue to be assessed using RECIST 1.1 until disease progression and then followed up for survival.
  Assessments for survival should be made every 8 weeks following objective disease progression. The details of first and subsequent therapies for cancer, after discontinuation of treatment, will be collected.

Eligibility: Inclusion Criteria:
  1. Advanced solid cancers (including histologically or cytologically documented gastric cancer, colorectal cancer, hepatoma, biliary tract cancers, pancreatic cancer and rare cancers.) that has progressed after standard chemotherapy.
  - Rare cancers are defined as sarcoma, neuroendocrine carcinoma
  2. Provision of tumor sample tumor sample tumor sample tumor sampletumor sample (from either a resection or biopsy)
  3. Patients with RICTOR amplification through NGS.
  4. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
  Exclusion Criteria:
  1. Patients not having received recommended treatment-lines and chemotherapy regimen for the treatment of each tumor type in the advanced setting.
  2. Any previous treatment with PIK3CA, AKT or mTOR inhibitor or agents with mixed PI3K / mTOR activity.
  3. HER2 positive AGC patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +)

Relevance to patient case: not relevant
Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: Efficacy of Postoperative Adjuvant Chemotherapy for Stage II Colon Cancer With High Risk Factors(EPAC1)

Summary: The purpose of this study is to design a prospective randomized clinical trial to explore whether postoperative adjuvant chemotherapy may provide survival benefit for stage II colon cancer patients with high risk factors.Therefore the investigators can provide high level clinical evidence of indications for patients with colon cancer with stage II colon cancer.

Detailed description: The most controversial of adjuvant chemotherapy for colon cancer is whether stage II colon cancer should receive adjuvant chemotherapy or not. Because of the absolute little benefit of adjuvant chemotherapy after curative resection of stage II colon cancer，NCCN and ESMO guidelines do not recommend routine adjuvant chemotherapy for patients with stage II colon cancer unless combined with high risk factors.
  Currently，most studies about stage II colon cancer with high risk factors were retrospective. Some suggested that patients with stage II colon cancer can benefit from adjuvant chemotherapy, however, more got the negative conclusions.
  The study was designed as a multicenter, prospective, randomized, controlled trial.Patients who agreed to participate in the study would be randomly assigned to a treatment group of adjuvant chemotherapy or observation with 50% chance by a central randomization system determined by the computer program.
  After a follow up of at least 3 years, the disease free survival of the two groups will be compared.

Eligibility: Inclusion Criteria:
  1. aged 18 to 75 years;
  2. pathologically confirmed adenocarcinoma of the colon
  3. after curative resection pathological stage was T3-4N0M0;
  4. with at least one of the following factors:
  1. T4 staging
  2. lymph nodes number less than 12
  3. poor differentiation (except MSI-H)
  4. LVI or PNI
  5. obstruction or perforation
  6. Elevated preoperative serum CEA
  5. ECOG Performance status 0-1
  6. no evidence of distant metastases
  7. no preoperative chemotherapy or chemoradiation therapy
  8. ANC > 1.5 cells/mm3, HGB > 10.0 g/dL, PLT > 100,000/mm3, total bilirubin ≤ 1.5 xULN, AST≤ 3 x ULN, ALT ≤ 3 x ULN.
  9. Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study.
  Exclusion Criteria:
  1. combined with other cancer
  2. Creatinine level greater than 1.5 times the upper limit of normal.
  3. Patients who have received preoperative chemotherapy or chemoradiotherapy.
  4. Patients with a history of a prior malignancy within the past 5 years.
  5. Women who are pregnant or breast-feeding.
  6. patients may not complete the whole schedule of chemotherapy
  7. Patients with any other concurrent medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study.

Relevance to patient case: not relevant
Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: Impact of Adjuvant Chemotherapy in Patients With Colon Cancer

Summary: The present study aims to investigate the impact of adjuvant chemotherapy with 5-FU isolated and associated with oxaliplatin in cardiac autonomic control and endothelium-dependent vascular function in patients undergoing colectomy for stages II and III colon cancer. Will be performed evaluation of cardiac and vascular function, autonomic control, functional capacity and blood evaluations.

Detailed description: Cancer is a major public health problem. Colorectal cancer is the third most common cancer in men and women around the world. Despite advances in surgical and pharmacological treatment, this type of cancer remains a leading cause of cancer death in Western countries. The adjuvant chemotherapy treatment based on the use of fluoropyrimidine, especially 5-fluorouracil (5-FU) is the mainstay of the pharmacological treatment of colorectal cancer. This treatment showed benefit in overall survival and progression-free survival in the adjuvant treatment of patients with stage II and III disease. In the last decade, the combination treatment with oxaliplatin has shown benefit in patients with either metastatic disease as with locoregional disease who underwent surgical treatment. However, the increased use of 5-FU and oxaliplatin, and increased patient survival have caused increased incidence of adverse events. 5-FU has cardiotoxic effects that may range from 1.2 to 18% depending upon the drug administration. Another adverse event of chemotherapy for colon cancer is neurotoxicity. Peripheral neuropathy is one of the toxicities associated with treatment with Oxaliplatin and its characteristics to be dose-dependent and cumulative. Thus, the adjuvant chemotherapy with 5-FU and oxaliplatin may cause cardiotoxicity, changes in vascular function and increased oxidative stress. What is not known are the effects of treatment of 5-FU and oxaliplatin in cardiac autonomic modulation and peripheral vascular function. Therefore, the present study aims to investigate the impact of adjuvant chemotherapy with 5-FU isolated and associated with oxaliplatin in cardiac autonomic control and endothelium-dependent vascular function in patients undergoing colectomy for stages II and III colon cancer. Will be performed evaluation of cardiac and vascular function, autonomic control, functional capacity and blood evaluations.

Eligibility: Inclusion Criteria:
  -  Scale of Performance Status 0 - 1
  -  Patients submitted to colectomy for adenocarcinoma of colon stages II and III.
  Exclusion Criteria:
  -  Severe pulmonary disease
  -  Decompensated cardiovascular disease
  -  Neurological disease
  -  Insulin-dependent diabetes mellitus
  -  Dialysis renal insufficiency

Relevance to patient case: not relevant