araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 56-year-old female with melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: Study to Evaluate the Safety and Efficacy of BA058 (Abaloparatide) for Prevention of Fracture in Postmenopausal Women

Summary: The purpose of this study is to determine whether BA058 (abaloparatide), a parathyroid hormone-related peptide, is effective in preventing fractures in postmenopausal women with severe osteoporosis who are at risk of fractures.

Detailed description: This is a randomized, double-blind, placebo-controlled, comparative Phase 3, multicenter international study to evaluate the efficacy and safety of BA058 (abaloparatide) 80 µg in the prevention of fracture in otherwise healthy ambulatory postmenopausal women with severe osteoporosis.

Eligibility: Inclusion Criteria:
  -  Healthy ambulatory postmenopausal (≥ 5 years) women from 50 to 85 years of age (inclusive) with a diagnosis of osteoporosis
  -  The women are to have a bone mineral density (BMD) T score ≤ -2.5 and > -5.0 at the lumbar spine or hip (femoral neck) by dual energy x-ray absorptiometry (DXA) and radiological evidence of 2 or more mild or one or more moderate lumbar or thoracic vertebral fractures, or history of low trauma forearm, humerus, sacral, pelvic, hip, femoral, or tibial fracture within the past 5 years. Postmenopausal women older than 65 who meet the above fracture criteria but have a T score ≤ -2.0 and > -5.0 may be enrolled. Women older than 65 who do not meet the fracture criteria may also be enrolled if their T score is ≤ -3.0 and > -5.0
  -  Normal physical exam, vital signs, electrocardiogram (ECG) and medical history
  -  Laboratory tests within the normal range including serum calcium, PTH(1-84), serum phosphorus and alkaline phosphatase
  Exclusion Criteria:
  -  History of more than 4 mild or moderate spine fractures or any severe fracture
  -  Abnormality of the spine or hip that would prohibit assessment of bone mineral density (BMD)
  -  Unexplained elevation of serum alkaline phosphatase, history of bone disorders (such as Paget's disease) or a diagnosis of cancer within the last 5 years (with the exception of basal cell or squamous cancer of the skin)
  -  History of thyroid, parathyroid, or adrenal disorders, or malabsorptive syndromes or any chronic or recurrent diseases or disturbances that would interfere with the interpretation of study data or compromise the safety of the patient
  -  Prior treatment with parathyroid hormone (PTH) or parathyroid hormone-related peptid (PTHrP)
  -  Prior treatment with bisphosphonates, fluoride, or strontium within the past five years or treatment with androgens, anabolic steroids, corticosteroids or selective estrogen receptor modulators within the past 12 months (except hormone replacement therapy)
  -  Prior treatment with an investigational drug within the past 12 months
  -  History of nephrolithiasis or urolithiasis within the past five years, or history of osteosarcoma at any time

Relevance to patient case: not relevant
Patient case: 56-year-old female with melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases

Summary: This open-label, single-arm, multicenter study will evaluate the efficacy and safety in participants with metastatic melanoma who developed brain metastases. Participants may or may not have received prior systemic treatment for metastatic melanoma [except treatment with v-raf murine sarcoma viral oncogene homolog B (BRAF) or mitogen-activated protein kinase (MEK) inhibitors]. Participants will receive oral doses of 960 mg vemurafenib twice daily until disease progression, unacceptable toxicity or consent withdrawal.


Eligibility: Inclusion Criteria:
  -  Adult participants, >/= 18 years of age
  -  Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) with BRAF V600 mutation (cobas 4800 BRAF V600 Mutation Test)
  -  Measurable brain metastases, defined as lesions that were accurately measured in at least one dimension (longest diameter to be recorded) as ≥0.5 cm in the brain MRI with contrast, treated or untreated
  -  Participants may or may not have received prior systemic therapy for metastatic melanoma and either a) have received no prior treatment for brain metastases or b) have received prior treatment for brain metastases and have progressed
  -  Participants may or may not have symptoms related to their brain metastases
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  -  Participants must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma
  Exclusion Criteria:
  -  Increasing corticosteroid dose during the 7 days prior to first dose of study drug
  -  Leptomeningeal involvement in participants with no prior treatment for brain metastases
  -  Previous malignancy requiring active treatment within the past 2 years, except for treated and controlled basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix
  -  Concurrent administration of any anticancer therapies other than those administered in the study
  -  Treatment with any cytotoxic, investigational drug or targeted therapy 4 weeks prior to first dose of study drug. Radiation therapy ≤1 week prior to first administration of vemurafenib; and stereotactic radiotherapy ≤1 day prior to prior to first administration of vemurafenib
  -  Prior treatment with BRAF or MEK inhibitors
  -  Clinically significant cardiovascular disease or event within the 6 months prior to first dose of study drug

Relevance to patient case: not relevant
Patient case: 56-year-old female with melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma

Summary: CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.


Eligibility: Inclusion Criteria:
  For the dose escalation phase:
  1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]). For the dose expansion phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or (ii) confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC) for which no further effective standard therapy exists.
  2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
  3. Evidence of measurable disease
  Exclusion Criteria:
  1. Previous therapy with a MEK inhibitor.
  2. Symptomatic or untreated leptomeningeal disease.
  3. Symptomatic or untreated brain metastasis.Patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastasis must be stable with verification by imaging.
  4. Known acute or chronic pancreatitis.
  5. Clinically significant cardiac disease
  6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818
  7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
  8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
  9. History of thromboembolic or cerebrovascular events within the last 6 months
  Other protocol-defined inclusion/exclusion criteria may apply

Relevance to patient case: not relevant
Patient case: 56-year-old female with melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors

Summary: In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma and patients with other solid tumors will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide.

Detailed description: In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma (n=6) will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma (n=9) and patients with other solid tumors (n=6) will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide. AdCD40L is given by weekly injections of 2.5x10e11 VP, 4x; total dose 1x10e12 VP. A maximum of 30 patients will be included in this trial.
  AdCD40L is an adenoviral nonreplicating vector carrying the human CD40L gene. AdCD40L infects tumor cells upon intratumoral injection and deliver the CD40L gene into the cells whereupon the virus is destroyed. CD40L is then expressed as a membrane-bound protein and interacts with the CD40 receptor expressed by for example dendritic cells (DCs) in the tumor area. DCs mature upon CD40/CD40L interactions and activates tumor-specific T cell responses.

Eligibility: Inclusion Criteria:
  -  Histologically proven diagnosis of malignant solid cancer, ECOG 0-2.
  -  Disease progression on established treatments or patients not eligible to standard options.
  -  Signed informed consent must be obtained.
  Exclusion Criteria:
  -  Pregnancy.
  -  Life expectancy less than 3 months.
  -  Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
  -  Patients with severe systemic autoimmune disease.
  -  Patients that do not consent to that tissue and blood samples are stored in a biobank.

Relevance to patient case: not relevant
Patient case: 56-year-old female with melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: Thoratec's Reduce Driveline Trauma Through Stabilization and Exit Site Management Study

Summary: The purpose of this study is to evaluate the feasibility of a Percutaneous Lead Management Kit for HeartMate II driveline stabilization and exit site management.

Detailed description: The Percutaneous Lead Management Kit is a combination of commercially available components that are packaged together in a kit to be used for HeartMate II driveline exit site cleaning, dressing and stabilization. The RESIST study is a prospective, non-randomized study to evaluate the wearability and usability of the Percutaneous Lead Management Kit. Evaluation of the Percutaneous Lead Management Kit for wearability and usability will be performed for 30 days from enrollment. Study patients will also be followed for up to 6 months for any evidence of driveline infection.

Eligibility: Inclusion Criteria:
  -  Signed informed consent form
  -  16 years of age or older
  -  Supported by HeartMate II LVAD continuously for at least 6 months and not currently hospitalized
  -  Will continue on LVAD support for at least another 30 days
  -  No driveline or systemic infection
  -  Willing and able to perform kit dressing changes at least once every 7 days for 30 days
  -  Can fill out study forms
  -  Can use a digital camera
  -  Willing to return to clinic for final study visit in 30 days
  Exclusion Criteria:
  -  High risk for non-compliance
  -  Ongoing mechanical circulatory support other than HeartMate II LVAD
  -  Sensitivity to kit components
  -  Skin condition that may react to kit component adhesives
  -  Already using all components of Percutaneous Lead Management Kit

Relevance to patient case: not relevant
Patient case: 56-year-old female with melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: Study on the Evolution of Genes Mutation Related With Gastrointestinal Stromal Tumors

Summary: Mutations of tumor-related genes are dynamic. Gastrointestinal stromal tumor cells often are obviously more invasive in case of recurrence. The great majority of relapses may be associated with secondary mutation in the GIST related genes. Full gene sequences of c-KIT、PDGFRA and DOG1, which is extracted from the specimen cells of repeated surgical resection or biopsy tissue in GIST patients with postoperative recurrence, are analyzed with the screening-sequencing approach, in order to investigate the characteristics and variations associated with the different gene mutations of c-KIT、PDGFRA and DOG1 in GIST patients and be likely to find out the evolutionary pattern, try to learn the facts about the effect of tyrosine kinase inhibitors on the GIST related genes, make a survey of any association of c-KIT、PDGFRA and DOG1 gene mutations and provide the basis for seeking molecular marker of GIST for monitoring course of disease, and offer a theoretical basis and new therapeutic strategies for application of clinical treatment.


Eligibility: Inclusion Criteria:
  -  patients with Gist at the Department of Gastrointestinal and Glands Surgery of the First Affiliated Hospital of Guangxi Medical University in China.
  Exclusion Criteria:
  -  patients with hepatitis and tuberculosis

Relevance to patient case: not relevant
Patient case: 56-year-old female with melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: cKIT, BRAF/NRAS Mutations in Advanced Melanoma : Clinical Outcome in Response to Tyrosine-kinase Inhibitors - KitMel Project

Summary: Background: Metastatic melanoma has a devastating prognosis and is one of the top causes of cancer death in young patients. Until now, available therapies were few and unreliable, but recent understanding of melanomas' molecular pathways has improve their classification and new clinical strategies have been proposed.
  Initial studies showed that B-Raf/N-Ras mutations (respectively V600E and Q61) are the most frequent alteration being present in 70 to 80% of melanomas, characterizing non Chronic Sun-induced Damage skins (CSD). These include Superficial Spreading Melanomas (SSM) and Nodular Melanomas (NM). Other studies showed that c-Kit mutations are presently the predominant activating mutation (20 - 40 %) in Acro-Lentiginous Melanomas (ALM), Mucous Melanomas (MM) and in melanomas arising on CSD skin. c-Kit mutation pattern is more complex with four exons being affected leading to different mutations, which incidence and biological impact are less documented.
  BRAF/NRAS genetics alterations drive constantly cell growth, being thus attractive targets. Spectacular results have indeed been obtained with the BRAF inhibitor that targets the V600E BRAF-mutated form. Data from GIST disease revealed that the different c-Kit mutations modulate differently c-Kit function and the response to targeted therapies.
  Because c-Kit targeted therapy is a critical clinical issue, the investigators aimed to identify the most frequent mutations present in our population to propose appropriate screening test and adapt the therapy.
  Methods: 250 melanoma samples corresponding to an homogeneous white-Caucasian population (Brittany, France) will be screened. c-Kit exons 11, 13, 17 and 18 will be sequenced (direct sequencing and pyrosequencing when possible). c-Kit copy number will be quantified by q-PCR and level of c-Kit determined by immunohistochemistry (IHC, CD117). Samples will also be analyzed for B-Raf mutations in codon 464, 466, 469 and 600, and for N-Ras mutations in codon 12, 13 and 61 (Pyrosequencing).
  Expected Results:
  Taken together, the investigators anticipate that the present genetic analysis of the tumours from patients with advanced melanoma will first document the type and frequency of cKit mutations, will confirm or not that BRAF, NRAS and cKit mutations are mutually exclusive and document their repartition in the melanomas sub-types. Finally this study will clue researchers in to how well patients will respond to a therapy that targets the growth-promoting proteins BRAF/NRAS and cKIT.


Eligibility: Inclusion Criteria:
  -  melanoma
  -  white caucasian population

Relevance to patient case: possibly relevant
Patient case: 56-year-old female with melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: Study of Circulating Tumor Cells Before and After Treatment in Patients With Metastatic Melanoma

Summary: Circulating tumor cells (CTC) are the subject of increasing interest in clinical oncology as a prognostic factor and predictor of therapeutic response. The detection of CTC by immunomagnetic method has proved its reliability and its usefulness for monitoring breast cancer, colon and prostate in the metastatic and immunomagnetic detection system (CellSearch, Veridex LLC) was approved by the FDA in these indications. However, to date there is no reliable method to detect CTCs in melanoma (CMC). Studies based on PCR amplification of mRNA by reverse specific melanoma is disappointing. Recently, a new detection system of CMC immunomagnetic was presented (CellSearch, Veridex LLC, United States). This system has the advantage of combining immunomagnetic selection step and a step of identifying by immunofluorescence. A preclinical study on serial dilutions of melanoma cells has shown encouraging results. The investigators propose a prospective study of the CellSearch system in patients with melanoma.
  Primary objective: To determine the effect of treatment on the number of circulating melanoma cells in patients with metastatic melanoma.
  Secondary objectives:
  -  determine the percentage of patients with metastatic melanoma with melanoma cells circulating
  -  seek a relationship between the number of circulating melanoma cells and prognosis in patients with metastatic melanoma
  -  seek a relationship between the change in the number of circulating melanoma cells before / after treatment and tumor response in patients with metastatic melanoma


Eligibility: Inclusion Criteria:
  -  Patients > or = 18 years
  -  Patients with advanced melanoma stage IIIC (unresectable) or stage IV
  -  Patient not treated or not responding to chemotherapy with chemotherapy session last> 1 month
  -  Patients who signed informed consent
  -  Patients presenting no socio-economic, psychological, familial or geographical allow proper understanding of the information leaflet of the protocol or the regular monitoring in the department of dermatology
  -  Patients with a life expectancy greater than 3 months
  -  Patients with melanoma measurable by RECIST version 1.1
  -  Patients with venous good for venipuncture
  Exclusion Criteria:
  -  Patients with contraindication for treatment with chemotherapy or V600E BRAF inhibitor or ipilimumab or have conditions concomitant heavy may interfere with the treatment of metastatic melanoma
  -  Pregnant women or nursing
  -  People vulnerable detainees, adults under guardianship or curatorship, minors.

Relevance to patient case: not relevant
Patient case: 56-year-old female with melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: Self-sampling and Human Papillomavirus (HPV)-Testing for Unscreened Women in Cervical Cancer Prevention

Summary: Scientific Context:
  High-risk types of human papillomavirus (HPV) are the causative agents for cervical cancer. Cervical cancer screening strategies rely on periodic Papanicolaou (Pap) testing. It's well-known that this test has significantly contributed to the reduction of mortality and morbidity due to cervical cancer. In France, it now seems that the screening strategy could be optimized. The two main ways are to reach the 7 million underscreened women (organized screening, self-sampling for HPV DNA testing) and to improve the screening test (HPV DNA testing, computer-assisted cytology). Self-collected vaginal samples (SCVS) for HPV DNA testing could be a relevant screening option: this technique appears reliable and it could allow to reach women who are never or seldom screened. The performance of the SCVS to detect cervical HPV infection has been assessed by the first part of the whole study: APACHE-1.
  The goal of this study is to compare the attitudes of women not attending organized cervical cancer screening face to different strategies: further invitation to make a cervical smear or kit for self-collected vaginal sample sent at home.
  Description of the project :
  Nine months after a primary invitation to make a cervical smear, a random sample of 6000 women not attending organized cervical cancer screening will be randomly assigned to one of the following arms:
  -  Intervention arm 1:
  Women will receive a further invitation to make a cervical smear
  -  Intervention arm 2:
  Women will be directly sent the kit for self-collected vaginal sample at home. The women who will send the self-sample to the laboratory for analyse will receive their results at home as well as their general practitioner if the HPV DNA test is positive (infection by a high-risk HPV).
  For them who will have a HPV DNA test positive, it will be necessary to complete the screening action with a cervical smear. That's why those women will receive an invitation to make a cervical smear if they won't do it during the 9 months following the first mail.
  -  Control arm: Those women will receive complete information about the study, the main results and the screening recommendations at the end of the study.


Eligibility: Inclusion Criteria :
  -  Women from 30 to 65 years
  -  Living in Indre-et-Loire (french territorial division 37)
  Exclusion Criteria :
  -  Women who attend organized cervical cancer screening or who answer to the invitation
  -  Cervical smear made in the three last years
  -  HPV linked cervical condition undergoing treatment
  -  Hysterectomy (including cervix)

Relevance to patient case: not relevant