araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: Study of PF-05212384 (Also Known as PKI-587)Administered Intravenously To Subjects With Solid Tumors

Summary: This is a two-part study of a compound called PF-05212384 (also known as PKI-587). The purpose of part 1 is to identify the Maximum Tolerated Dose (MTD) of PF-05212384 using a Continual Reassessment Method (CRM). Part 1 will include subjects with any solid tumor. In Part 2 two cohorts will be enrolled. One cohort will assess safety, tolerability and preliminary efficacy in 20 subjects at the MTD and will include subjects with breast cancer, ovarian cancer, endometrial cancer, colorectal cancer renal cancer or glioblastoma (a type of brain tumor). The other cohort will include 5 to 15 subjects with any type of tumor who consent to provide tumor biopsies while participating in the study.


Eligibility: Inclusion Criteria:
  -  Pathologic diagnosis of any solid tumor
  -  Incurable cancer, with disease progression following at least 1 therapy with no further standard treatment available in the opinion of the investigator.
  -  At least 1 evaluable lesion per RECIST criteria
  Exclusion Criteria:
  -  Clinically unstable primary or metastatic CNS tumors
  -  Subjects with known diabetes
  -  QTc interval greater than 470 ms.

Relevance to patient case: possibly relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: A Study of PI3-Kinase Inhibitor GDC-0941 in Combination With Paclitaxel, With and Without Bevacizumab or Trastuzumab, and With Letrozole, in Participants With Locally Recurrent or Metastatic Breast Cancer

Summary: This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of oral (PO) pictilisib administered with letrozole or intravenous (IV) paclitaxel with and without IV bevacizumab or IV trastuzumab in participants with locally recurrent or metastatic breast cancer. The study consists of three parts. Part 1 (pictilisib will be administered in 21+7 schedule along with paclitaxel and/or bevacizumab), Part 2 (pictilisib will be administered in 5+2 schedule along with paclitaxel and/or bevacizumab or trastuzumab) and Part 3 (pictilisib will be administered in combination with letrozole). Part 1 and Part 2 consists of two stages; a dose escalation stage and a cohort-expansion stage.


Eligibility: Inclusion Criteria:
  -  Confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease
  -  Adequate organ and bone marrow function as assessed by laboratory tests
  -  Evaluable disease or disease measurable per RECIST
  -  Agreement to use an effective form of contraception for the duration of the study
  Exclusion Criteria:
  -  History of malabsorption syndrome or other condition that would interfere with enteral absorption
  -  Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytic agents
  -  Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, radiotherapy, or hormonal therapy) within 4 weeks or 5 half-lives (whichever is shorter) of the first dose of study treatment
  -  Uncontrolled current illness
  -  Active small or large intestine inflammation (such as Crohn's disease or ulcerative colitis)
  -  Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
  -  Known HIV infection
  -  New York Heart Association (NYHA) Class II or greater congestive heart failure
  -  Active ventricular arrhythmia requiring medication
  -  Pregnancy, lactation, or breastfeeding
  -  Known significant hypersensitivity to study drugs or excipients
  -  History of arterial thromboembolic disease within 6 months of first study treatment
  -  No more than two prior chemotherapy regimens for metastatic disease

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: A Study to Assess the Efficacy and Safety of Lenalidomide in Combination With Cetuximab in Pre-treated Patients With KRAS Mutant Colorectal Cancer

Summary: The purpose of this study is to determine whether lenalidomide in combination with cetuximab is safe and effective in patients with KRAS mutant colorectal cancer.


Eligibility: Inclusion Criteria:
  1. Metastatic colorectal adenocarcinoma.
  2. Confirmed K-RAS mutant tumor
  3. Disease progression on oxaliplatin- AND irinotecan-containing regimens, with at least one of these regimens containing bevacizumab.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
  Exclusion Criteria:
  1. Use of chemotherapy, hormonal therapy, immunotherapy or any other cancer or experimental treatment ≤ 28 days prior to the first day of the first cycle.
  2. Radiotherapy for up to ≥ 30% of the bone marrow.
  3. Surgery ≤ 28 days before day 1 of the first cycle (minimally invasive interventions for diagnostic purposes or disease staging are permitted).
  4. Previous treatment with cetuximab, panitumumab, pomalidomide (CC-4047), lenalidomide or thalidomide.
  5. Untreated, symptomatic brain metastases (brain imaging not required).
  6. Venous thromboembolism ≤ 6 months before day1 of the first cycle.
  7. Current congestive heart failure (classes II to IV of the New York Heart Association).
  8. Myocardial infarction ≤ 12 months before day1 of the first cycle.
  9. Uncontrolled hypertension.

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: Safety of BKM120 Monotherapy in Advanced Solid Tumor Patients

Summary: This is a first-in-man, phase I clinical research study with BKM120, a potent and highly specific oral pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor. The study consists of a dose escalation part followed by a MTD expansion part.
  Once the MTD has been defined, the MTD expansion part will be opened for enrollment.


Eligibility: Inclusion Criteria:
  All patients:
  -  Histologically-confirmed advanced solid tumors
  -  Progressive, recurrent unresectable disease
  -  World Health Organization (WHO) Performance status ≤ 2
  -  No history of primary brain tumor or brain metastases
  MTD Expansion part:
  -  Histologically-confirmed advanced solid tumors
  -  Progressive, recurrent unresectable disease
  -  World Health Organization (WHO) Performance status ≤ 2
  -  No history of primary brain tumor; no brain metastases unless asymptomatic and clinically stable for ≥ 3 months
  -  Patients with genetic or molecular alteration of the PI3K pathway
  Exclusion Criteria:
  -  Prior treatment with a PI3K inhibitor
  -  History of or active major depressive episode, bipolar disorder, schizophrenia, or history of suicidal attempt or ideation
  -  No clinically manifest diabetes mellitus (treated and/or with clinical signs)
  -  No acute or chronic renal disease
  -  No acute or chronic liver disease
  -  No acute or chronic pancreatitis
  -  No unresolved diarrhea
  -  No impaired cardiac function or clinically significant cardiac diseases such as ventricular arrhythmia, congestive heart failure, uncontrolled hypertension
  -  No acute myocardial infarction or unstable angina pectoris within the past 3 months
  -  Not pregnant or nursing and fertile patients must use barrier contraceptives
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: Neoadjuvant Treatment of Colon Cancer

Summary: This study will investigate
  -  the effect of preoperative combination chemotherapy in patients with locally advanced colon cancer with mutation in the KRAS, BRAF or PIK3CA gene
  -  the effect of preoperative combination chemotherapy in combination with biological treatment in patients without mutation in the KRAS, BRAF or PIK3CA gene.


Eligibility: Inclusion Criteria:
  -  Histologically verified locally advanced T3 or T4 colon cancer assessed by CT scan
  -  Analysis of KRAS, BRAF, PIK3CA
  -  Age ≥18 år
  -  Performance status ≤ 2
  -  Hematology
  -  ANC ≥ 1.5x10^9/l. Thrombocytes ≥ 100x10^9/l.
  -  Biochemistry
  -  Bilirubinaemia ≤ 3 x UNL. ALAT ≤ 5 x UNL
  -  Consent to translational research
  -  Fertile women must present a negative pregnancy test and use secure birth control during and 3 months after treatment.
  -  Written and orally informed consent.
  Exclusion Criteria:
  -  Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment, active severe infections or other concurrent disease.
  -  Peripheral neuropathy NCI grade >1
  -  Other malignant disease within 5 years prior to enrollment, except basal cell squamous carcinoma of the skin and cervical carcinoma-in-situ
  -  Other investigational treatment within 30 days prior to treatment start
  -  History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
  -  Bleeding tumors
  -  Hypersensitivity to one or more of the substances

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: An Observational Study to Evaluate the Safety and Efficacy of FOLFIRI / FOLFOX Plus Cetuximab as First-line Therapy in Patients With KRAS Wild-type Metastatic Colorectal Cancer

Summary: This is an open-label, non-randomized, prospective, multicentric, Phase IV study evaluating FOLFIRI/ FOLFOX plus cetuximab in the first-line therapy of subjects with KRAS wild-type metastatic CRC.

Detailed description: Cetuximab, a chimeric immunoglobulin G1 (IgG1) monoclonal antibody, has been found to potentiate the effects of chemotherapy and radiotherapy in experimental systems. The findings from clinical trials suggest a favorable risk-benefit ratio of the combination of irinotecan or oxaliplatin, infusional 5-FU/FA and biweekly cetuximab, and support the current study to demonstrate the therapeutic value of the biweekly cetuximab regimen as a combination partner for those regimens in subjects with KRAS wild-type mCRC in the first-line setting. The purpose of this study is to generate post marketing surveillance (PMS) data for cetuximab in first-line mCRC, which is mandated by the Licensing Authorities.
  This is an open-label, non-randomized, prospective, multicentric Phase IV study evaluating FOLFIRI/ FOLFOX plus cetuximab in the first-line therapy of subjects with KRAS wild-type metastatic CRC. The study plans to enroll 100 subjects with KRAS wild type CRC at 20 centres across India. Tumour status, physical and laboratory examinations will be performed during the baseline visit. Subjects will be administered FOLFIRI/ FOLFOX and cetuximab according to the clinical condition in the following treatment visits. Regular safety assessments and all adverse events (AEs) will be documented throughout and until the end-of-study visit. The outcome of AEs ongoing at the final tumour assessment visit will be followed up at the end-of-study visit (If possible, 6 weeks after the last administration of study medication but before second-line anticancer treatment, and not earlier than 30 days after the end of study treatment). Skin toxicity present at the end-of-study visit will be followed up until outcome is known.
  OBJECTIVES
  Primary Objective:
  -  To evaluate the safety and tolerability of Cetuximab in combination with standard chemotherapy such as FOLFOX or FOLFIRI as first-line therapy of patients with KRAS wild-type metastatic colorectal cancer.
  Secondary Objective:
  -  To evaluate the efficacy of Cetuximab in combination with standard chemotherapy as first-line therapy of patients with KRAS wild-type metastatic colorectal cancer.

Eligibility: Inclusion Criteria:
  -  Subjects with histologically confirmed, adenocarcinoma of the colon or rectum (mCRC)
  -  Subjects with KRAS wild-type status of tumour tissue
  -  Chemotherapy naïve subjects
  -  Subject who have signed written informed consent (as per institutional protocol)
  Exclusion Criteria:
  -  As per summary of product characteristics of cetuximab

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: KRAS Mutation and Incidence of the Colorectal Carcinoma in Martinique Between 2007 and 2009

Summary: -  There is no data at present concerning the KRAS mutation in patients from Martinique with colorectal cancer. Despite the fact that the incidence of this disease continues to increase there is no recent data to confirm it. This study has a descriptive purpose, allowing a comparison of the population from Martinique to other populations.
  -  A study of incidence of colorectal cancer, overseen by the Association from Martinique for the Epidemiological Search on Cancer (AMREC), also leads to a better knowledge of the local characteristics of the colorectal cancer.
  -  These two descriptive characteristics of colorectal cancer in Martinique will be useful data for the health professionals to provide their patients better care.

Detailed description: -  The colorectal carcinogenesis is complex. It influences among others, the EGFR (Epidermal Growth Factor Receptor) which activation leads to tumoral proliferation, differentiation and invasion. The binding of the EGF (Epidermal Growth Factor) or of another ligand to the EGFR is responsible for the activation of the Ras- Raf and Pi3k pathways.
  -  The mutation of the genes KRAS, BRAF or PIK3CA results in their continuous activation, independently of the activation or of the pharmacological blocking of EGFR. The most frequently found mutation affects the KRAS gene (20 to 50 % of the cases). 90 % of these mutations are situated on codons 12 and 13 of this gene (70 % codon 12 and 30 % codon 13). These mutations are responsible for a decrease of the GTPase activity of the ras protein, which stays then in active conformation bound to the GTP. This leads to the blocking of the pathway and to the inactivity of the pharmacological blocking of EGFR.

Eligibility: Inclusion Criteria:
  -  for the study of the KRAS mutation: 250 patients drawn by lots among the cases of colorectal carcinoma diagnosed between January 1st, 2007 and December 31st, 2009 in Martinique
  -  for the study of incidence: patient for whom was diagnosed a colorectal carcinoma between January 1st, 2007 and December 31st, 2009
  -  patient unopposed and in free agreement to participate in this study
  -  patient having his main home in Martinique at the time of the diagnosis
  -  patient 18 years old and over
  Exclusion Criteria:
  -  patient whose diagnosis is prior to 2007 and later in 2009
  -  patient having shown opposition to the participation in this study
  -  patient minor or under guardianship
  -  patient not having his main home in Martinique at the time of the diagnosis

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: Pemetrexed in Advanced Non-small Cell Lung Cancer

Summary: Present study is aimed at investigating potential molecular predictors of sensitivity or resistance to single-agent pemetrexed in the ≥ second line setting in a large cohort of advanced non-small cell lung cancer (NSCLC) patients. The following biomarkers will be investigated with either immunohistochemistry, fluorescence in situ hybridization or genotyping: thymidylate synthase (TS), dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyl transferase (GARFT), aminoimidazole carboxamide ribonucleotide formyltransferase (ATIC/AICARFT), epidermal growth factor receptor (EGFR), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), v-myc myelocytomatosis viral oncogene homolog (MYC) and phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA).


Eligibility: Inclusion Criteria:
  -  Histologically confirmed diagnosis of advanced non-small cell lung cancer - Tumor tissue available at our institution
  -  Patients treated with single agent pemetrexed for metastatic disease
  -  Availability of full clinical data
  Exclusion Criteria:
  -  Cytological diagnosis of advanced Non-small cell lung cancer
  -  Lack of tumor tissue at our institution
  -  Lack of full clinical data

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: Combination Chemotherapy Plus Panitumumab or Bevacizumab for Inoperable Cholangiocarcinoma Without KRAS Mutations

Summary: The purpose of this study is to determine the rate of progression free survival of patients with inoperable cholangiocarcinoma 6 months after enrollment in the study. The patients are treated with combination chemotherapy supplemented by biological agents panitumumab or bevacizumab.


Eligibility: Inclusion Criteria:
  -  Histologically verified adenocarcinoma arisen from gall bladder, extra- or intrahepatic bile ducts or malignant cells consistent with the above and simultaneous radiologic findings consistent with cholangiocarcinoma
  -  Minimum 18 years of age
  -  Curative treatment currently not an option (operation, stereotactic radiation treatment or similar)
  -  KRAS analyzed and found wild-type (wt)
  -  Performance status 0-2
  -  Evaluable disease according to RECIST, i.e. the disease need not be measurable
  -  Hematology: ANC ≥1.5x10^9/l. Thrombocytes ≥ 100x10^9/l
  -  Biochemistry: Bilirubinemia ≤ 3 x upper normal level. ALAT ≤ 5 x upper normal level.
  -  Creatinine ≤ upper normal level. At raised creatinine level the measured or calculated GFR must be at least 50% of the lower normal level
  -  Fertile women must present a negative pregnancy test and use secure birth control during and 6 months after treatment. Men with fertile partners must also take care of secure birth control.
  -  Written and orally informed consent
  Exclusion Criteria:
  -  Previous cytostatic treatment of inoperable cholangiocarcinoma
  -  Adjuvant or neoadjuvant chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to treatment start
  -  Other concomitant experimental treatment
  -  Severe medical disease such as considerable heart disease, serious active infection or other disease making the patient unfit for study participation as assessed by investigator
  -  Other malignant disease within 5 years prior to enrolment except from non-melanotic skin cancer and carcinoma in situ cervicis uteri
  -  Interstitial pneumonitis or subsequent pulmonary fibrosis
  -  Pregnant or breastfeeding women
  -  Large-scale surgical intervention, excision biopsy or significant traumatic lesions within 28 days prior to treatment start or presumption that large-scale surgery will become necessary during study treatment.
  -  Significant non-healing wound or ulcers
  -  Active hemorrhage or increased risk of hemorrhage (e.g. tumor invasion in large vessels or known esophagus varices)
  -  Known hypersensitivity to panitumumab, bevacizumab or any of the auxiliary agents
  -  Grade IV fistulas
  -  Uncontrolled hypertension, i.e. symptomatic hypertension or non-medically stabilized hypertension >160/100
  -  Haemoptysis > 2.5 ml within 2 weeks prior to enrolment
  -  Previous serious and unexpected reactions or know hypersensitivity to two or more of the applied cytostatics

Relevance to patient case: not relevant
Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene

Summary: This is a first-in-man trial, in which BYL719 will be administered to adult patients with advanced solid tumors, whose tumors have an alteration of the PIK3CA gene and whose disease has progressed despite standard therapy or for whom no standard therapy exists. A combination of BYL719 with fulvestrant will also be investigated in post-menopausal patients with locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene. The single agent MTD dose expansion cohort and the fulvestrant combination MTD dose expansion cohort will also include ER+/HER2- breast cancer patients whose tumors have the wild type PIK3CA gene


Eligibility: Inclusion Criteria:
  -  Patients with histologically-confirmed, advanced unresectable solid tumors who have progressed within three months before screening/baseline visit Only patients who have confirmed PIK3CA status (wild type, mutation or amplification) will be allowed for screening (patients participating in the combination arm must be eligible for treatment with fulvestrant)
  -  Availability of a representative formalin fixed paraffin embedded tumor tissue sample
  -  At least one measurable or non-measurable lesion
  -  Age ≥ 18 years
  -  World Health Organization (WHO) Performance Status ≤ 2
  -  Good organ (hepatic, kidney, BM) function at screening/baseline visit
  Exclusion Criteria:
  -  Brain metastasis unless treated and free of signs/symptoms attributable to brain metastasis in the absence of corticosteroid therapy (anti-epileptic therapy is allowed).
  -  Prior treatment with PI3K, AKT or mTOR inhibitor and failure to benefit
  -  Patient with peripheral neuropathy NCI-CTC Grade ≥ 3
  -  Patient with diarrhea NCI-CTC Grade ≥ 2
  -  Patient with acute or chronic pancreatitis
  -  Impaired cardiac function or clinically significant cardiac disease incl. unstable angina pectoris ≤ 3 months prior to starting study drug and Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug.
  -  Patients with clinically manifest diabetes mellitus, history of gestational diabetes mellitus or documented steroid-induced diabetes mellitus
  -  Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: possibly relevant