araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Study of Dabrafenib+Trametinib in the Adjuvant Treatment of Stage III BRAF V600+ Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes

Summary: This is an open-label Phase IIIb study of dabrafenib in combination with trametinib in the adjuvant treatment of melanoma after complete resection to evaluate the impact on pyrexia related outcomes of an adapted pyrexia AE-management algorithm, as well as safety, efficacy and health-related outcomes.
  Approximately 600 subjects will be enrolled to receive dabrafenib (150 mg BID) and trametinib (2 mg once daily) combination therapy for 12 months. At enrollment, subjects will be instructed on the pyrexia management algorithm.
  This study consists of two Periods for Enrolled subjects:
  -  Treatment Period - subjects will receive up to 12 months of treatment.
  -  Follow-up Period - subjects will be followed through 24 months from their first dose date for relapse, and through end of study for overall survival. Follow-up will start once treatment is complete or is prematurely discontinued and continue through the end of the study, regardless of disease recurrence.


Eligibility: Inclusion Criteria:
  -  Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)]
  -  V600E/K mutation positive using a validated local test
  -  Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
  -  Subjects who have previously had Stage III melanoma at any time are not eligible.
  -  Subjects with an unknown primary melanoma are not eligible.
  -  Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
  Exclusion Criteria:
  -  Uveal or mucosal melanoma
  -  Evidence of metastatic disease including unresectable in-transit metastasis
  -  Received any prior adjuvant or neoadjuvant treatment, including but not limited to chemotherapy, checkpoint inhibitors, targeted therapy [e.g., BRAF and/or MEK inhibitors], biologic therapy, vaccine therapy, investigational treatment, or radiotherapy for melanoma
  -  Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ
  -  History or current evidence of cardiovascular risk
  -  A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: A Biospecimen Collection Study in BRAF-V600E Mutated Recurrent Gliomas

Summary: This is a surgical biospecimen collection study. The purpose of this study is to understand how much of two drugs (dabrafenib and trametinib) are able to penetrate brain tumors and turn off the RAF signaling pathway. This is important because these drugs are currently FDA approved for other tumors and may have efficacy in brain tumors with the BRAF V600E mutation.

Detailed description: The primary goal of this study is to establish concentrations of dabrafenib and trametinib in enhancing brain tissue and cerebrospinal fluid from people with BRAF-V600E mutant recurrent gliomas who undergo tumor resection. The exploratory goals are to measure the amount of ERK signaling pathway activity, to identify mechanisms of resistance to these drugs, and evaluate feasibility of measuring tumor DNA in cerebrospinal fluid.
  People (adults or children) with brain tumors who are already taking dabrafenib and / or trametinib and are in need of a surgical resection are potentially eligible. On the day of surgery, blood, cerebrospinal fluid, and tumor tissue will be collected for research purposes.

Eligibility: Inclusion Criteria:
  -  Subjects must have a history of primary brain tumor (including but not limited to glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic ganglioglioma (AG), and anaplastic pleomorphic xanthoastrocytoma (PXA)).
  -  Subjects must have a BRAF-V600 mutation identified in previous tissue analysis (may be IHC or PCR based). Allowable mutations include V600E, V600K, V600R, and V600D.
  -  Subjects must be taking dabrafenib at a dose of at least 50mg twice daily (adults only) and / or trametinib at a dose of at least 1mg daily (adults only) for at least 7 days prior to surgery as prescribed by their treating physician. Note: Pediatric patients may be taking any dose of dabrafenib and / or trametinib as prescribed by their treating physician for at least 7 days prior to surgery.
  -  Subjects must be undergoing surgery for clinical purposes.
  -  Written informed consent - a signed informed consent and/or assent (as age appropriate) for study participation will be obtained according to institutional guidelines.
  Exclusion Criteria:
  -  Subjects who are receiving any other investigational agents or chemotherapeutic agents.
  -  Subjects for whom collection of blood, spinal fluid, or tissue samples is unsafe or clinically inadvisable.

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: A Phase 1, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation.

Summary: Evaluate the safety and tolerability of AMG 510 in adult subjects with KRAS p.G12C mutant solid tumors.
  Estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose [RP2D]) within investigated subject population groups.


Eligibility: Inclusion Criteria:
  -  Men or women greater than or equal to 18 years old.
  -  Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12Cmutation identified through DNA sequencing.
  -  Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
  Exclusion Criteria:
  -  Active brain metastases from non-brain tumors.
  -- History or presence of hematological malignancies unless curatively treated with no evidence of disease
  -  Myocardial infarction within 6 months of study day 1.
  -  Symptomatic congestive heart failure (New York Heart Association greater than class II)
  -  Unstable angina
  -  Cardiac arrhythmia requiring medication
  -  Gastrointestinal (GI) tract disease causing the inability to take oral medication.
  -  Active infection requiring intravenous (IV) antibiotics within 1 weeks of study enrollment (day 1)
  -  Positive Hepatitis B Surface Antigen (HepBsAg) or positive Hepatitis total core antibody with negative HepBsAg
  -  Detectable Hepatitis C virus
  -  Known positive test for HIV
  -  Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (Grade 2 or 3 toxicities from prior anti-tumor therapy that are considered irreversible [defined as having been present and stable for greater than 6 months] may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and sponsor)

Relevance to patient case: not relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Neoadjuvant mFOLFOXIRI for Potentially Resectable Cholangiocarcinoma

Summary: Previous reports suggest benefit of neoadjuvant chemotherapy/chemoradiation treatment for borderline resectable cholangiocarcinoma. This study is a single center prospective phase II study of neoadjuvant chemotherapy with mFOLFOXIRI in patients with borderline resectable cholangiocarcinoma.

Detailed description: Previous reports suggest benefit of neoadjuvant chemotherapy/chemoradiation treatment for borderline resectable cholangiocarcinoma.
  This study is a single center prospective phase II study of neoadjuvant chemotherapy with mFOLFOXIRI in patients with borderline resectable cholangiocarcinoma.
  This phase 2 trial was designed to enroll 25 patients with BRCC who were assigned to mFOLFOXIRI neoadjuvant chemotherapy. The primary endpoint was the overall response rate.

Eligibility: Inclusion Criteria:
  1. ≥ 18 years old at the time of informed consent
  2. Diagnosed with cholangiocarcinoma and the disease is measurable by RECIST 1.1 criteria
  3. ECOG performance status of 0 or 1
  4. No distant metastasis
  5. The disease is either resectable or potentially resectable
  6. Patients must have adequate organ function as defined by the following laboratory values at study entry:
  Hemoglobin ≥ 8 g/dL (transfusions are acceptable) ANC ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L AST/ALT ≤ 3 x ULN Total bilirubin ≤ 2.5 mg/dL Creatinine clearance ≥ 50 mL/min (estimated by Cockcroft-Gault or measured)
  7. Women of childbearing potential definition (WOCBP) and men must agree to use adequate contraception prior, to study entry, for the duration of study participation, and 3 months after the end of treatment.
  8. WOCBP must have a negative serum or urine pregnancy test prior to initiation of treatment.
  Exclusion Criteria:
  1. > 75 years old
  2. Prior therapy for cholangiocarcinoma with either surgery, radiation or chemotherapy
  3. Other malignancies except for the following: adequately treated cervical carcinoma in situ and treated basal cell carcinoma.
  4. Hypersensitivity to 5FU, oxaliplatin (or other platinum agents), irinotecan (or to their excipients).
  5. Pregnant or lactating women.
  6. Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  7. Liver disease including but not limited to cirrhosis, primary sclerosing cholangitis, future liver remnant of less than 20-30%
  8. Comorbidity including but not limited to active clinically serious infections, congestive heart failure, life-threatening arrhythmia
  9. known HIV positive
  10. Baseline peripheral neuropathy/paresthesia grade ≥ 2.

Relevance to patient case: not relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer

Summary: Cancer immunotherapy with immunostimulatory antibodies targeting the CTLA-4 or PD-1/PD-L1 pathways has demonstrated its efficacy in variable proportions of cancer. For metastatic colorectal cancer (mCRC) it appeared that only the small subgroup of patients with MSI-H tumors (microsatellite instability-high phenotype) had a clinically meaningful response to the anti-PD-1- L1 antibodies. In the majority group of non-MSI-H CRC (90-95% of patients), current research expect that additional means would be able to render the tumor "immunogenic" (like MSI-H CRC) and increase the intratumoral immune infiltrate which is the prerequisite to observe a benefit from PD1-PD-L1 inhibitors. Combinations of immune checkpoint inhibitors and procedures that increase intratumoral immune responses, such as targeted therapy, are actively explored.


Eligibility: Inclusion Criteria:
  -  Age 18 and over, Performance status: ECOG 0-1
  -  Histologically proven metastatic colorectal adenocarcinoma, refractory to standard chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan) and anti-EGFR treatment (only for RAS WT tumor)
  -  Measurable disease (RECIST 1.1)
  -  Metastasis accessible for sequential biopsies
  -  Patient consent for metastasis biopsies in the study protocol
  -  BRAF V600E wild-type and MSS tumors
  -  Adequate normal organ and marrow function (see adequate section of the full protocol for definition)
  -  Life expectancy of at least 4 months
  Exclusion Criteria:
  -  Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy that are not indicated in the study protocol
  -  Systemic autoimmune disease,
  -  Chronic treatment with corticoids or other immunosuppressive treatment
  -  Clinically significant cardiac, lung or general disease despite optimal treatment
  -  Non-progressive disease following irinotecan-based treatment.
  -  For RAS WT, non-progressive disease following anti-EGFR treatment.

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; 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: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Safety of ADU-1604 in Adults With Metastatic Melanoma

Summary: This study is a first-in-human, open-label, multicenter, dose-escalation study designed to evaluate the safety, PK, and PD of ADU-1604 and explore initial clinical activity in adults with metastatic melanoma.

Detailed description: ADU-CL-17 is a first-in-human, open-label, multicenter, dose-escalation study designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ADU-1604, an anti-CTLA-4 monoclonal antibody, and explore initial clinical activity in adults with metastatic melanoma. The primary objective of the study is to determine the Recommended Phase 2 Dose (RP2D) of ADU-1604 administered by IV infusion once every 3 weeks for 4 doses.
  The study will be conducted in two parts: Dose Escalation followed by Dose Confirmation.

Eligibility: Inclusion Criteria:
  1. Male or female aged ≥18 years
  2. Histologically-confirmed metastatic or unresectable melanoma
  3. Progression of disease following at least one prior therapy, and is not a candidate for, or is intolerant to, established therapy known to provide clinical benefit (i.e. available treatment options have been exhausted). Subjects must have BRAF mutation status confirmed; if a subject is BRAF V600E/K positive, they must have received a BRAF- targeted regimen prior to entering the study, unless the patient was deemed ineligible for such treatment
  4. Measurable disease according to RECIST (v1.1) [NOT required during Dose Escalation]
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  Exclusion Criteria:
  1. Prior diagnosis of uveal or mucosal melanoma
  2. Prior treatment with CTLA-4-directed therapy in the metastatic setting. Use of CTLA- 4-directed treatment in the adjuvant or neoadjuvant setting is acceptable provided the last dose was >6 months before the first dose of ADU-1604 and there was no discontinuation of treatment due to a treatment-related toxicity.

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; 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: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: A Study of the Role of Circulating Tumor DNA in Predicting the Likelihood of Organ Preservation After Clinical Complete Response to Neoadjuvant Therapy for Rectal Cancer

Summary: In this research study, the investigators are looking to see if the circulating tumor DNA (genetic material), also known as ctDNA, in the blood will help them predict whether the participant's cancer will come back.

Detailed description: In this research study, the investigator are performing blood draws to see if the presence or absence of circulating tumor DNA (ctDNA), the genetic material in the participant's cancer's cells, will help the investigators predict whether the participant's cancer will come back or not.

Eligibility: Inclusion Criteria:
  -  Participants must have achieved a clinical complete response (cCR) within 3 months of last therapy - defined as absence of residual ulceration, mass or mucosal irregularity at endoscopic assessment - following neoadjuvant therapy with chemoradiation or chemotherapy followed by radiation for stage I, II, or III non-metastatic rectal cancer. (Whitening of the mucosa with presence of telangiectasia will be accepted as cCR.)
  -  Participants must have original tumor tissue (formalin-fixed, paraffin-embedded specimens) available for analysis
  -  Participants must be 18 years of age or older.
  -  Participants must be able to understand and willing to sign a written informed consent document.
  -  Participants must have received long course chemoradiation to 40-54 Gy.
  -  Participants must have received at least 4 cycles of FOLFOX
  -  Participant must be no more than 3 months past the conclusion of initial chemoradiation of rectal cancer (i.e., end of chemoradiation).
  Exclusion Criteria:
  -  Participants may not have any other organ cancer evident at the time of enrollment.
  -  Participants may not have any other concurrent serious illness that makes participation on this study impractical or clinically inappropriate.

Relevance to patient case: possibly relevant
Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Chemothetapy FORFIRINOX in Advanced or Recurrent Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma

Summary: The purpose of this study is to evaluate the feasibility, efficacy and safety of FORFIRINOX in advanced or recurrent extrahepatic cholangiocarcinoma and gallbladder carcinoma.

Detailed description: The purpose of this study is to evaluate the feasibility, efficacy and safety of FORFIRINOX in advanced or recurrent extrahepatic cholangiocarcinoma and gallbladder carcinoma.

Eligibility: Inclusion Criteria:
  -  • Chinese；
  -  Stable vital signs, KPS≥60;
  -  Patients have a diagnosis of advanced or recurrent metastatic extrahepatic cholangiocarcinoma or gallbladder carcinoma by histopathology or cytopathology, who are not suitable for radical surgery or have progressed R1 resection or palliative surgery;
  -  Adequate fresh tumor tissue for genome sequencing and immuno- histochemistry test; harboring mutations or abnormal activation of erb-b2 receptor tyrosine kinase signal pathway components;
  -  At least one measurable and evaluable site of disease according to the RECIST criteria version 1.1;
  -  Life expectancy of more than 12 weeks;
  -  Adequate hepatic, hematologic and renal functions(ALT≤10×upper limit of normal (ULN), AST≤10×ULN, the Child-Pugh classification for class A or B, white blood cells≥3×10^9/L, neutrophils≥1.5×10^9/L, platelets≥80×10^9/L , hemoglobin ≥ 90g/L, creatinine clearance rate≥60ml/min;
  -  Volunteer for this study, have written informed consent and have good Patient compliance;
  -  Female patients of childbearing potential and their mates agree to avoid pregnancy.
  Exclusion Criteria:
  -  Have received following treatment before this study:
  1. Anti-tumor molecular target therapy; anti-tumor chemotherapy in 6 months;
  2. lesions have been treated by irradiation;
  3. participate in other therapeutic or interventional clinical trials. - Page 5 of 5 [DRAFT] -
  -  Have central nervous system metastasis;
  -  History of other malignancies except carcinoma in-situ of uterine cervix, cured basal cell carcinoma of skin and other malignancies for more than 5 years;
  -  Have symptomatic ascites and need for treatment;
  -  Have serious concurrent illness including, but not limited to
  1. uncontrolled congestive heart failure(NYHA classification grade III or IV), unstable angina pectoris, unstable cardiac arrhythmias, uncontrolled moderate or serious hypertension(systolic blood pressure >21.3 Kpa or diastolic blood pressure >13.3 Kpa);
  2. ongoing or active serious infection;
  3. uncontrolled diabetes mellitus;
  4. psychiatric illness which potentially hamper the ability to willingly give written informed consent and compliance with the study protocol;
  5. HIV infection;
  6. other serious illness considered not suitable for this study by investigators.
  -  be allergic or have contraindications to target medicines involved in this study, gemcitabine or oxaliplatin.

Relevance to patient case: not relevant