araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: Study of the Variations of Albumin Level for Patients With Unresecable Stage IIIc or Stage IV Melanoma Treated by Anti BRAF and Anti MEK

Summary: The therapeutic arsenal of metastatic melanoma has changed considerably over the past 10 years. The treatment of metastatic melanoma is now based on immunotherapy and targeted therapies, while the place of conventional chemotherapy becomes more restricted. Targeted therapies are indicated for BRAF mutated melanomas.
  The mutation BRAF leads activation of MAP Kinases pathway and the proliferation of melanoma cell in the body . About 50% of metastatic melanoma is BRAF mutated. The most frequent mutation is the V600E. The targeted therapy by anti BRAF and anti MEK allows the double bloking of the MAP Kinases pathway. This treatment is more efficient than that of the anti BRAF alone. The association of anti BRAF and anti MEK have a global survival global rate of 41% at the 1 year, against 9% for the anti BRAF .
  In 2014, a program of extended access to the association of anti BRAF and anti MEK (dabrafenib and trametinib) started in many french hospitals (Protocol Mekinist, Novartis laboratory). Patients who were included in this program and followed in Poitiers Hospital, had frequent abnormalities of albumin level without any sign of undernutrition.
  Hypoabuminemia is a poor prognosis factor described in many cancers, including metastatic melanoma.
  The only prognostic factor in metastatic melanoma is the rate of LDH . The level of albumin and its prognostic impact have not been studied for patients with a metastatic melanoma and treated by anti BRAF and anti MEK.
  The objective of this studie was to analyze the variations of albumin level in patients with unresecable stage IIIc or stage IV melanoma treated in our Center by dabrafenib and trametinib


Eligibility: Inclusion Criteria:
  -  Age > 18 ans
  -  the patients with unresecable stage IIIc or IV melanoma with BRAF V600 E or K mutation,
  -  treated by dabrafenib and trametinib by the program of extended access (research protocol Mekinist)
  Exclusion Criteria:
  -  Age < 18 ans
  -  patients who had less than 3 months of treatment,
  -  patients for which the albumin level could not be carried out before starting treatment, and after the first month

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: Collection of Blood, Urine, and Stool to Monitor MetastaticColorectal Cancers

Summary: This trial studies the monitoring of therapy and progression by collecting blood, urine, and stool from participants with colorectal cancer that has spread to other places in the body or cannot be removed by surgery. Studying samples of blood, urine, and stool from participants with colorectal cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer.

Detailed description: PRIMARY OBJECTIVES:
  I. Detection of mutated Kras in urine specimen of patients with Kras mutated metastatic colon cancer on first, second, or third line therapy.
  II. Detection of new Kras in urine in patients without Kras mutated metastatic colon cancer on therapy which includes anti-EGFR antibodies (cetuximab or panitumumab).
  SECONDARY OBJECTIVES:
  I. Changes of the stool microbiome with chemotherapy and at progression of the disease.
  DESCRIPTIVE OBJECTIVES:
  I. Changes in the quantity of mutated Kras, Braf or PI3K in urine deoxyribonucleic acid (DNA) over the cycles of first line therapy.
  II. Associations between the quantity of mutated Kras, Braf or PI3K in urine DNA, molecular make up of circulating tumor cells (CTCs), cell free DNA and progression over the course of first line therapy.
  III. Feasibility of detection of exosome in the plasma of colorectal cancer patients on first line chemotherapy in Dr. Fabbri?s lab at Children?s Hospital Los Angeles.
  IV. Feasibility of detection of tumor DNA in the plasma of colorectal cancer patients on first line chemotherapy.
  OUTLINE:
  Participants undergo collection of blood and urine at baseline, on day 1 of courses 1, 2, and 3, at restaging, and at disease progression. Participants may undergo collection of stool at baseline, on day 1 of course 2, and at disease progression. Participants also undergo biopsy within 4 weeks of disease progression.

Eligibility: Inclusion Criteria:
  -  All patients with metastatic/unresectable colorectal cancer who will undergo first, second, or third line therapy; the participating investigator will select treatment, however, patients with Kras wild type must receive anti-EGFR therapy to be eligible for this study
  -  Subject consent to enrollment on the protocol
  -  Histologically confirmed metastatic or un-resectable colorectal cancer, known Kras status; knowledge of other mutations is optional
  -  Willingness to undergo biopsy at the time of progression
  -  Willingness to follow the study instructions for collection of specimens
  -  Available archival tissue

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors

Summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).

Detailed description: This is an open-label, multicenter, Phase 1 study of oral RMC-4630 monotherapy in participants with advanced relapsed or refractory solid tumors. The study will include 2 components: 1) a Dose-Escalation Component for participants with relapsed or refractory solid tumors and 2) a Dose-Expansion Component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the RAS-MAPK pathway. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

Eligibility: Inclusion Criteria:
  -  Participant (male or female) ≥18 years of age
  -  Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  -  Participants in the Dose-Expansion Component must have one of the following genotypic aberrations: RTK mutations, amplifications or rearrangements, KRASG12, BRAF Class 3, or NF1 LOF mutations
  -  Adequate hematologic, hepatic and renal function
  -  Participant able to understand and voluntarily sign the informed consent form (ICF) and able to comply with the study visit schedule and other protocol requirements.
  -  Participants willing to agree to not father a child/become pregnant and comply with effective contraception criteria
  Exclusion Criteria:
  -  Known or suspected leptomeningeal or brain metastases or spinal cord compression
  -  Primary central nervous system (CNS) tumors
  -  Clinically significant cardiac disease
  -  Active, clinically significant interstitial lung disease or pneumonitis
  -  History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO
  -  Known HIV infection
  -  Active/chronic hepatitis B or C infection
  -  Any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy
  -  Females who are pregnant or breastfeeding

Relevance to patient case: possibly relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior VEGFR-targeted Therapy

Summary: The objective of this study is to evaluate the effect of cabozantinib compared with placebo on progression free survival (PFS) and objective response rate (ORR) in subjects with Radioiodine-Refractory Differentiated Thyroid Cancer (DTC) who have progressed after prior VEGFR-Targeted therapy.


Eligibility: Inclusion Criteria:
  1. Histologically or cytologically confirmed diagnosis of Differentiated Thyroid Cancer (DTC)
  2. Measurable disease according to RECIST 1.1
  3. Previously treated with or deemed ineligible for treatment with Iodine- 131 for DTC
  4. Previously treated with at least one of the following VEGFR-targeting TKI agents for DTC: lenvatinib or sorafenib. Note: Up to two prior VEGFR-targeting TKI agents are allowed
  5. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1
  Exclusion Criteria:
  1. Prior treatment with any of the following: Cabozantinib; Selective small-molecule BRAF kinase inhibitor; More than 2 VEGFR-targeting TKI agents; More than 1 immune checkpoint inhibitor therapy; 1 systemic chemotherapy regimen (given as single agent or in combination with another chemotherapy agent)
  2. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks or 5 half-lives of the agent, whichever is longer, before randomization
  3. Receipt of any type of anticancer antibody (including investigational antibody) or systemic chemotherapy within 4 weeks before randomization
  4. Receipt of radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before randomization.
  5. Known brain metastases or cranial epidural disease unless adequately treated

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: FIVC in Advanced Colorectal Cancer Patients With BRAF V600E Mutation.

Summary: This clinical trial aims to evaluate the efficacy, safety of FOLFIRI with vemurafenib and cetuximab in Advanced Colorectal Cancer Patients with BRAF V600E mutation.


Eligibility: Inclusion Criteria:
  -  Patients should be histologically diagnosed with advanced colorectal adenocarcinoma or postoperative recurrence;
  -  Patients with BRAF V600E mutation and extended RAS wild type;
  -  Patients have measurable lesions;
  -  Patients are not available for targeted therapy or patients refuse to receive targeted therapy;
  -  Age should be 18-25 years;
  -  Performance status should be 0-2;
  Exclusion Criteria:
  -  Patients with RAS mutation type;
  -  Patients with brain metastases;
  -  Patients could not tolerate chemotherapy;
  -  Patients have secondary primary tumor

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: A PhaseI Study of HL-085 Plus Vemurafenib in Solid Tumor With BRAF V600 Mutation

Summary: This is a phase I, open-label, dose escalation study to evaluate tolerability, safety, pharmacokinetics and efficacy in patients with BRAF V600 mutant advanced solid tumor by HL-085 plus Vemurafenib treatment.


Eligibility: Inclusion Criteria:
  1. BRAF V600 mutation in solid tumor.
  2. One measurable lesion as defined by RECIST 1.1 criteria for solid tumors.
  3. Chemotherapy, immunotherapy or radiotherapy ≥ 4 weeks prior to starting the study treatment.
  4. Surgery (except for tumor biopsy) or severe trauma ≤ 14 days prior to starting the study treatment.
  5. ECOG performance status of 0-1.
  6. Life expectancy ≥ 3 months.
  7. Ability to take the medicine orally.
  8. Ability to understand and the willingness to sign a written informed consent document.
  Exclusion Criteria:
  1. Hypersensitivity to study drug ingredients or their analogues.
  2. Prior therapy with MEK-inhibitor.
  3. Receiving any other anti-cancer therapy at the same time .
  4. Active central nervous system (CNS) lesion.
  5. Bleeding symptoms at Grade 3 within 4 weeks prior to starting study treatment.
  6. ECG QTcB≥480msec in screening, or history of congenital long QT syndrome；
  7. Uncontrolled concomitant diseases or infectious diseases.
  8. Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.).
  9. History of HIV,HCV,HBV infection.
  10. Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded.
  11. Serum HCG test is positive.
  12. Other conditions that increase the risk of study and influence the result.

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: Preclinical Validation of New Anti-melanoma Compounds

Summary: This research program is in keeping with the chemistry/biology/clinical interface and gathers 4 teams with complementary expertise in these respective fields. It will allow deciphering the mechanism(s) of action of new Thiazole-Benzenesulfonamide family (TZB) derivatives on metastatic melanoma sensitive and resistant to BRAF and MEK inhibitors. Investigators will use melanoma cell lines and primary cells from patients to validate these compounds in collaboration with clinical team 2 and 4. In conclusion, the investigators expect to establish the proof of concept that this new class of bioactive molecules (first in class) we developed in collaboration with Team 3 have the potential to go to the clinic for the treatment of highly aggressive cancers and particularly metastatic melanoma sensitive and resistant B-Raf and MEK inhibitors. Furthermore, the realization of this project can undoubtedly increase the knowledge of mechanisms and signaling pathways that are involved in resistant to BRAF and MEK inhibitors, and allow the selection of drug candidates capable of restoring the sensitivity of these melanoma cells.


Eligibility: Inclusion Criteria:
  -  Patient with metastatic melanoma
  -  Not opposition of the patient will have been looked for
  Exclusion Criteria:
  -  Primary resistance,
  -  Absence of resistance,
  -  Patient already included in other trials

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: A Multicenter Trial of Radiofrequency Ablation vs. Surgery as Treatment of Papillary Thyroid Microcarcinoma.

Summary: The treatment of Papillary Thyroid Microcarcinoma (PTMC) nowadays varies among physicians, surgeons and radiologist. The recently published articles show that the prognosis of PTMC by different means of treatment strategies tends to be good. But multicentered, randomized, parallel and prospective study is rare. RFA is the abbreviation of "Radiofrequency Ablation", which tends to be an alternative strategy except conventional surgery. The investigator aims to confirm whether RFA for treating PTMC braces same effectiveness and prognosis comparing with conventional surgery. Besides, this trial also investigates the safety, economy and psychological quality under different treatments.

Detailed description: The incidence of thyroid carcinoma, especially the papillary thyroid microcarcinoma (PTMC), has increasingly rapidly, due to the development of technologies of diagnosis, during the past 20 years. PTMC defined by the World Health Organization (WTO) as the largest dimension less than 1 cm. Previous autopsy study demonstrated that the lesions are normal in many people and accompany them latently until they die because of another reasons. The long-term outcome of PTMC is good and, as expected, more than 90% PTMC aren't progress for many years.
  Ultrasound-guided Radiofrequency Ablation (RFA) treatment was introduced to clinical practice few years ago. According to the 2015 American Thyroid Association (ATA) guideline, the treatment of radiofrequency and laser ablation are mentioned to be used in recurrent thyroid cancer. But clinical practice shows that the RFA treatment for low risk PTMC braces well effect，low financial budget，high safety and even rare postoperative complication.
  Although the cohort study was performed before, the real answer concerning about whether RFA is a rational choice for treating PTMC lacks more powerful evidences. The investigator considers to perform a randomized, controlled and multicenter study as a high-quality evidence and demonstrated the effect of PRF in low risk PTMC treatment.

Eligibility: Inclusion Criteria:
  -  Newly diagnosis of PTMC (largest dimension<10mm)
  -  Age >=18 years old
  -  Bethesda Category V or VI
  -  Single nodule without thyroid capsule contact
  -  Nodule has more than 3mm distance far from recurrent laryngeal nerve, carotid artery and trachea.
  -  No clinical evidences show there is local or distant metastasis.
  -  Without chemotherapy, radiotherapy and other related therapies.
  -  Patients and their family member totally understand and sign the informed consent.
  Exclusion Criteria:
  -  Multifocal PTMC
  -  Combined with other types of thyroid cancer or hyperthyroidism.
  -  Contralateral vocal cord paralysis
  -  With local or distant metastasis
  -  Pregnant woman
  -  With radiation exposure history

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: Sub-type Specific Genomic Mutations in sBOTs

Summary: The aim of this study is to identify different origin in carcinogenesis between serous borderline ovarian tumors presenting a. without implants, b. with non-invasive implants, c. with invasive implants and d. with micropapillary pattern.
  The presence of specific mutations could suggest for a more aggressive primary treatment if a higher risk of recurrence can be expected.

Detailed description: Introduction Borderline Ovarian Tumors (BOTs) behave indolently in the vast majority of cases and the prognosis is usually favorable. There is more evidence that two subtypes of BOTs represent a higher risk of recurrence or even progression to an invasive ovarian cancer. In case of a presentation with a micro-papillary grow pattern or when invasive implants are diagnosed the prognosis tend to be less favorable.
  Genome sequencing in ovarian cancer helped to differentiate two different pathways in the carcinogenesis.
  Low grade serous carcinomas evolving from adenofibromas or borderline tumors over non-invasive micropapillary serous borderline tumors to invasive micropapillary serous carcinoma, show frequent mutations in the Kirsten Rat Sarcoma gene (KRAS), B-Raf Kinase gene(BRAF), Erb-B2 Receptor Tyrosine Kinase 2 gene (ERBB2), Phosphatase and Tensin homolog gene (PTEN), Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) and Catenin Beta 1 gene (CTNNB1). This pathway is called Type I and is characterized by a slow step-wise process. These low-grade invasive tumors are indolent and are known with a better outcome than high-grade invasive tumors.
  In contrast the Type II pathway development of invasive tumors is rapid and vast majority of tumors show a Tumor Protein p53 (TP53) mutation and loss of Breast Cancer type 1 susceptibility protein (BRCA1).
  The aim of this study is to identify different origin in carcinogenesis between serous borderline ovarian tumors presenting a. without implants, b. with non-invasive implants, c. with invasive implants and d. with micropapillary pattern.
  The presence of specific mutations could suggest for a more aggressive primary treatment if a higher risk of recurrence can be expected.

Eligibility: Inclusion Criteria:
  -  Paraffin embedded material from the original borderline ovarian tumor must be present and of good quality for DNA extraction.
  -  Original slides are available for central pathological review.
  Exclusion Criteria:
  -  Presence of invasive ovarian carcinoma.

Relevance to patient case: not relevant
Patient case: 51-year-old female with papillary thyroid carcinoma; genetic feature: BRAF (V600E)

Clinical trial: Folfirinox + Cetuximab Chemotherapy, in First Line, With Wild RAS and According to BRAF Status in Metastatic Colorectal Cancer

Summary: This retrospective study, will evaluate patient outcomes after triplet chemotherapy (FOLFIRINOX) (5 Fluorouracil + oxaliplatin + irinotecan) plus cetuximab 1st line treatment focusing on efficacy and safety in a RAS (KRAS, NRAS (neuroblastoma rat sarcoma viral oncogene homolog) wild-type metastatic colorectal cancer population, and according to BRAF (murine sarcoma viral oncogene homolog B) status and primary tumor location.

Detailed description: In Europe, there are 447,000 new cases of colorectal cancer each year. Approximately 25% of patients present with metastases at initial diagnosis and almost 50% of patients with mCRC (metastatic colorectal cancer) will develop metastases
  . Chemotherapy represents the backbone of treatment, and survival is linked with the administration of all three active cytotoxic agents (5-fluorouracil/folinate, oxaliplatin, and irinotecan) in the first line treatment of metastatic colorectal disease.
  Monoclonal antibodies such as cetuximab in combination with chemotherapy are a first line treatment option in metastatic RAS (rat sarcoma viral oncogene homolog) wild type metastatic colorectal cancer (mCRC).
  Phase II trials evaluating triplet chemotherapy plus cetuximab reported interesting results in terms of efficacy (response rate, resectability...), but at the price of an increased rate of toxic effects.
  This retrospective study, will evaluate patient outcomes after triplet chemotherapy (FOLFIRINOX) (5 Fluorouracil + oxaliplatin + irinotecan) plus cetuximab 1st line treatment focusing on efficacy and safety in a RAS (KRAS, NRAS (neuroblastoma rat sarcoma viral oncogene homolog) wild-type mCRC (metastatic colorectal cancer) population, and according to BRAF (murine sarcoma viral oncogene homolog B) status and primary tumor location.

Eligibility: Inclusion Criteria:
  1. Colorectal cancer confirmed as RAS wild by tumor tissue analysis
  2. Non resectable and measurable metastatic disease
  3. Patients treated with FOLFIRINOX + cetuximab in first line metastatic disease
  4. Males or females aged over 18 years.
  Exclusion Criteria:
  1. Known brain metastases
  2. RAS not assessable (e.g., material not available or insufficient)
  3. The first administration of cetuximab was more than 30 days after the first administration of FOLFIRINOX
  4. History of other malignancy in the last 5 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years

Relevance to patient case: not relevant