araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 64-year-old female with ovarian cancer; genetic feature: BRCA1

Clinical trial: Clinical and Histopathologic Characteristics of BAP1 Mutations

Summary: The goal of this protocol is to determine the prevalence of somatic and germline mutations in BAP1 (BRCA associated protein-1) among patients with mesothelioma , choroidal nevus, primary uveal melanoma (UM), or metastatic UM seen at our institution.


Eligibility: Inclusion Criteria:
  All consents:
  -  > or = to 18 years of age
  -  Ability to provide informed consent
  Consent 1:
  Mesothelioma
  -  Histologically proven diagnosis of Mesothelioma OR Choroidal nevus
  -  Diagnosis of choroidal nevus by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography OR Primary uveal melanoma
  -  Diagnosis of uveal melanoma by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography
  Consent 2:
  Mesothelioma
  -  Histologically proven diagnosis of Mesothelioma AND
  -  BAP1 mutation or loss of expression identified in tumor sample
  OR one of the following:
  -  Age<50 at diagnosis
  -  No history of asbestos exposure
  -  Personal history of choroidal nevus, uveal melanoma, melanoma, renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  -  History of malignancy in more than two first-degree relatives OR Choroidal nevus
  -  Diagnosis of choroidal nevus by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography AND one of the following:
  -  More than one clinical risk factor, which may include: orange pigment, thickness > 1 < 2.5mm
  -  Personal history of uveal melanoma, skin melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma OR Primary uveal melanoma
  -  Diagnosis of uveal melanoma by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography
  AND one of the following:
  -  Personal history of uveal melanoma, skin melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma
  -  History of malignancy in more than two first-degree relatives OR Metastatic uveal melanoma
  -  Histologically proven diagnosis of metastatic uveal melanoma AND
  -  BAP1 mutation or loss of expression identified in tumor sample
  OR one of the following:
  -  Personal history of uveal melanoma, skin melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  -  Family history of choroidal nevus, uveal melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma
  -  History of malignancy in more than two first-degree relatives
  Consent 3:
  -  Relative of patient with germline BAP1 mutation identified through identified testing
  Exclusion Criteria:
  -  none

Relevance to patient case: not relevant
Patient case: 64-year-old female with ovarian cancer; genetic feature: BRCA1

Clinical trial: A Maintenance Study With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer

Summary: This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of niraparib as maintenance in platinum sensitive ovarian cancer patients who have either gBRCAmut or a tumor with high-grade serous histology and who have responded to their most recent chemotherapy containing a platinum agent. Niraparib is an orally active PARP inhibitor. Niraparib or placebo (in a 2:1 ratio) will be administered once daily continuously during a 28-day cycle. Health-related quality of life will be measured by the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI), European Quality of Life scale, 5-Dimensions (EQ-5D), and a neuropathy questionnaire. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.
  The primary objective of this study is to evaluate efficacy of niraparib as maintenance therapy in patients who have platinum sensitive ovarian cancer as assessed by the prolongation of progression free survival (PFS).


Eligibility: Inclusion Criteria:
  -  18 years of age or older, female, any race
  -  Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer
  -  High grade (or grade 3) serous histology or known to have gBRCAmut
  -  Has received at least 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 6 month period between penultimate platinum regimen and progression of disease)
  -  Has responded to last the platinum regimen, remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen
  -  ECOG 0-1
  -  Adequate bone marrow, kidney and liver function
  Exclusion Criteria:
  -  Known hypersensitivity to the components of niraparib
  -  Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
  -  Symptomatic uncontrolled brain metastasis
  -  Is pregnant or breast feeding
  -  Immunocompromised patients
  -  Known active hepatic disease
  -  Prior treatment with a known PARP inhibitor

Relevance to patient case: definitely relevant
Patient case: 64-year-old female with ovarian cancer; genetic feature: BRCA1

Clinical trial: Prevention of Ovarian Cancer in Women Participating in Mammography

Summary: The primary purpose of this study is to evaluate the effect of systematic identification and genetic counseling referral on rates of bilateral salpingo-oophorectomy (surgery to remove both fallopian tubes and ovaries) in women having mammograms at Swedish Medical Center in Seattle, WA.


Eligibility: Inclusion Criteria:
  -  Prior mammogram at Swedish Medical Center
  -  Willing and able to provide informed consent, primary physician information, and complete study questionnaires
  -  Must meet at least ONE of the following criteria:
  -  personal history of breast cancer diagnosed before age 50
  -  personal history of bilateral breast cancer at any age
  -  1 or more first degree relatives with breast cancer diagnosed before age 50
  -  3 or more first or second degree relatives with breast cancer at any age
  -  2 second degree relatives with breast cancer diagnosed before age 50
  -  A male relative with breast cancer at any age
  -  Ashkenazi Jewish with any family history of breast or ovarian cancer
  -  1 first or second degree relative with ovarian cancer AND 1 first or second degree relative with breast cancer at any age
  -  2 first degree relatives with ovarian cancer or 2 second degree relatives with ovarian cancer or 1 first and 1 second degree relative with ovarian cancer.
  -  A first degree relative with both breast and ovarian cancer (2 primaries in the same person)
  -  Personal history of positive genetic test result for any of the following genes: BRCA1, BRCA2, HNPCC, or P53
  -  Family history of a positive genetic test result for any of the following genes: BRCA1, BRCA2 or HNPCC
  Exclusion Criteria:
  -  Previous diagnosis of ovarian cancer
  -  Prior bilateral-salpingo oophorectomy
  -  Had a negative genetic test result for a known family genetic mutation

Relevance to patient case: definitely relevant
Patient case: 64-year-old female with ovarian cancer; genetic feature: BRCA1

Clinical trial: Pharmacogenetics Of Vinorelbine In Malignant Pleural Mesothelioma Patients

Summary: This is a multicenter retrospective analysis .The aim of the present study is to investigate the molecular predictors of vinorelbine response in tumor samples of a series of MPM patients and evaluate the possible impact on clinical outcome.
  Sample size: around 150 patients based on the availability of tumor size

Detailed description: Vinorelbine has recently become an alternative option for palliation in selected pemetrexed-pretreated patients with malignant pleural mesothelioma (MPM). However, nowadays there are no definitive data about vinorelbine predictors of response in MPM patients. The identification of molecular predictors of effective therapy is important for maximizing therapeutic efficacy and minimizing useless treatment in cancer patients.
  In oncology a pharmacogenetic approach to customize the chemotherapy treatment according to individual as well as tumour genetic characteristics represents a modern and intriguing challenge. Recent studies have suggested that the expression levels of class III β-tubulin (TUBB3) or BRCA1, are related to a survival benefit from vinorelbine chemotherapy among patients with advanced solid malignancies, especially non-small cell lung cancer. There are no data about the predictive factors to vinorelbine in MPM patients. The identification of molecular predictors of effective therapy may allow in the future the development of better therapies.

Eligibility: Inclusion Criteria:
  -  MPM patients treated with vinorelbine in the ≥ second line setting will be retrospectively analyzed
  -  Patients will be selected based on the availability of tumor tissue
  Exclusion Criteria:
  -  NA

Relevance to patient case: not relevant
Patient case: 64-year-old female with ovarian cancer; genetic feature: BRCA1

Clinical trial: Adaptation to Living With a BRCA1/2 Mutation

Summary: Background:
  - Women who have a BRCA1/2 gene mutation have a very high risk of developing breast or ovarian cancer. They are also at increased risk of other developing other cancers. Male carriers are at increased risk for breast, prostate and other cancers. Testing for this mutation and living with this increased risk can be a source of stress for both people with the mutation and their partners. Researchers want to look at how well people adapt to living with this type of cancer risk over time.
  Objectives:
  - To see how women with the BRCA1/2 gene mutation and their partners adapt to the stress of long-term cancer risk.
  Eligibility:
  - Women at least 18 years of age who have a BRCA1/2 mutation, and their male or female partners.
  Design:
  -  This study involves a one-time self-administered questionnaire. Participants will be recruited from local and national hereditary cancer support groups and cancer centers.
  -  There are two versions of the survey. One is for the woman with the BRCA1/2 gene mutation. The other is for her partner.
  -  The survey will ask about risk perception, cancer worry, risk-related stress, and coping and adaptation methods.
  -  Treatment will not be provided as part of this study.

Detailed description: The proposed study aims to describe adaptation and dyadic adjustment in unaffected BRCA1/2 carriers and their partners. It is not fully understood how women and their partners adapt to highrisk status over time, nor how different aspects of living at risk relate to this process. Neither psychological adaptation nor dyadic adjustment has been systematically measured in this population. This study is informed by Lazarus & Folkman s Transactional Model of Stress and Coping and modifications made to this model for use in studying dyadic relationships. A crosssectional research design will quantitatively explore the relationships between the appraisals and timing of risk-related stressors, dyadic coping, and the outcomes of adaptation and dyadic adjustment. Participants will be recruited from hereditary breast and ovarian cancer (HBOC) support groups, website postings, listservs, and clinic patient lists. They will have the option of completing either a paper or online version of the survey.

Eligibility: -  INCLUSION AND EXCLUSION CRITERIA:
  Participants will be women aged 18 or older who have a BRCA1/2 mutation and their (male or female) partners. Carriers must have no personal history of cancer, but partners will not be excluded based on cancer history. Participants will be asked to disclose their mutation status (BRCA1 or BRCA2), but no screening evaluation will be required. If only one member of a couple completes the survey, their data will be included in the individual level analysis, but excluded from the dyadic level analysis.

Relevance to patient case: definitely relevant
Patient case: 64-year-old female with ovarian cancer; genetic feature: BRCA1

Clinical trial: BRCA1/2 and Effect of Mifepristone on the Breast

Summary: Ovarian steroids, as well as their synthetic counterparts gestagens and estrogens have a role in breast cell proliferation and the development of breast cancer. Here, the effect of a progesterone receptor modulator, mifepristone, on cell proliferation in human breast tissue in vivo will be studied in women with BRCA-1 or -2 mutations. Our preliminary results implicate a possible protective effect of mifepristone in breast epithelium. The ability of mifepristone to block breast epithelial cell proliferation may prevent tumorigenesis and may also prove beneficial when used for contraceptive purposes and on other indications. The proposed project concerns a Randomized Controlled Trial on mifepristone versus placebo treatment of women with BRCA-1or -2 mutations with a high risk/incidence of breast cancer and ovarian cancer.

Detailed description: Objectives • Research objective To study the safety and effect of treatment with mifepristone, a progesterone receptor modulator, on epithelial cell proliferation in human breast tissue in women with BRCA-1 or -2 mutations prior to protective mastectomy.
  Project description
  • Hypothesis/ Theory Mifepristone treatment exerts an antiproliferative, protective effect on breast tissue in women with BRCA-1 or -2 mutations
  Study Design Randomized, double blind, placebo controlled trial. Women will be recruited among patients with BRCA-1 or -2 mutations scheduled for prophylactic mastectomy. Included women will be randomized to a 3-month treatment with mifepristone, 50 mg (Mifegyne, Exelgyn, Paris, France) or placebo taken orally every second day. Breast biopsies will be obtained in the luteal phase prior to start of treatment and again during surgery.

Eligibility: Inclusion criteria:
  -  Pre-menopausal women, >/= 18 years of age
  -  with good general health and
  -  regular menstrual cycles (25-35 days) who are willing and
  -  able to participate after giving informed consent.
  -  women having BRCA1/2 mutation and have decided to undergo risk reducing mastectomy
  Exclusion criteria includes:
  -  Any hormonal treatment used within 2 months prior to study start and
  -  Any contraindication to mifepristone

Relevance to patient case: possibly relevant
Patient case: 64-year-old female with ovarian cancer; genetic feature: BRCA1

Clinical trial: Neratinib HER Mutation Basket Study (SUMMIT)

Summary: This is an open-label, non-randomized, multicenter, multinational, Phase 2 study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in patients with ERBB mutation-positive or EGFR gene-amplified solid tumors.

Detailed description: This is an open-label, multicenter, multinational, Phase 2 study exploring the efficacy and safety of neratinib therapy in patients with solid tumors with activating HER2, HER3 or EGFR mutations or with EGFR gene amplification.
  The trial will consist of a screening period, a treatment period, and an end of treatment visit occurring when neratinib is discontinued for any reason, a safety follow-up visit occurring 28 to 42 days after the last dose of neratinib and a survival follow-up period lasting for a maximum of 12 months for each patient after their last dose of neratinib or until initiation of additional anti-cancer therapy.

Eligibility: Inclusion Criteria:
  -  Histologically confirmed cancers for which no curative therapy exists.
  -  Documented HER2 mutation.
  -  Pediatric patients (at least 12 but less than 18 years of age at signing of informed consent) may be recruited in the Fibrolamellar Carcinoma cohort.
  Exclusion Criteria:
  -  Prior treatment with any pan-HER tyrosine kinase inhibitor (eg, lapatinib, afatinib, dacomitinib, neratinib).
  -  Patients who are receiving any other anticancer agents.
  -  Symptomatic or unstable brain metastases.
  -  Women who are pregnant or breast-feeding.
  Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Relevance to patient case: not relevant
Patient case: 64-year-old female with ovarian cancer; genetic feature: BRCA1

Clinical trial: Prostate Screening Study Using MRI in BRCA Carriers

Summary: Men with a BRCA1 or BRCA2 mutation are at increased risk for early onset, aggressive prostate cancer compared to men in the general population.
  Standard of care screening for men with a BRCA mutation includes PSA testing and digital rectal examination (DRE), the same as with men in the general population.
  This study is being done to assess whether there is value in using MRI as a screening tool to detect prostate cancer at an earlier stage than may otherwise be detected using standard of care screening (PSA, DRE). It is unclear whether MRI has utility as a screening tool in this specific population at high risk for aggressive disease.

Detailed description: To determine the value of using Multispectral 3T MRI (MS3TMRI) for prostate cancer screening in men with a high risk of developing early onset aggressive prostate cancer given known BRCA1 or BRCA2 mutation carrier status, with no prior prostate cancer diagnosis, independent of baseline PSA levels.
  -  Determine the prevalence of prostate cancer in BRCA1 and BRCA2 mutation carriers independent of baseline PSA levels.
  -  To evaluate the accuracy of tumor targeting based on MRI and ultrasound (US) tumor co-localization. To evaluate the sensitivity, specificity, PPV, NPV, and accuracy of an automated computer aided diagnosis method (CAD) applied to MS3TMRI in the prediction of zonal biopsy results for the presence or absence of a significant cancer.

Eligibility: Inclusion Criteria:
  -  Enrolled in the Male Hereditary Cancer Research Program at Sunnybrook Health Sciences Center.
  -  Have positive genetic testing for a pathogenic BRCA1 or BRCA2 mutation.
  -  Clinically eligible for and willing to undergo ultrasound biopsy within 4 weeks after the MRI.
  -  Be 50 years of age or older.
  Exclusion Criteria:
  -  Claustrophobia
  -  Contraindication to MRI
  -  Contraindication to receiving low molecular weight MRI contrast agent
  -  Previously diagnosed with prostate cancer

Relevance to patient case: not relevant
Patient case: 64-year-old female with ovarian cancer; genetic feature: BRCA1

Clinical trial: Assessment of the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.

Summary: This open label, randomised, controlled, multi-centre phase III study will assess the efficacy and safety of single agent olaparib vs standard of care based on physician's choice of capecitabine, vinorelbine or eribulin in metastatic breast cancer patients with gBRCA 1/2 mutations.


Eligibility: Inclusion Criteria:
  -  Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious.
  -  Histologically or cytologically confirmed breast cancer with evidence of metastatic disease.
  -  Prior therapy with an anthracycline and a taxane in either an adjuvant or metastatic setting.
  -  Prior platinum allowed as long as no breast cancer progression occurred on treatment or if given in adjuvant/neoadjuvant setting at least 12 months from last dose to study entry elapsed.
  -  ER/PR breast cancer positive patients must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy.
  -  ECOG performance status 0-1.
  -  Adequate bone marrow, kidney and liver function.
  Exclusion Criteria:
  -  Prior treatment with PARP inhibitor.
  -  Patients with HER2 positive disease.
  -  More than 2 prior lines of chemotherapy for metastatic breast cancer.
  -  Untreated and/or uncontrolled brain metastases.
  -  Prior malignancy unless curatively treated and disease-free for > 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix, DCIS or stage I grade 1 endometrial cancer allowed.
  -  Known HIV (Human Immunodeficiency Virus) infection.
  -  Pregnant or breast-feeding women.

Relevance to patient case: not relevant
Patient case: 64-year-old female with ovarian cancer; genetic feature: BRCA1

Clinical trial: A Study of Rucaparib in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation

Summary: The purpose of this study is to determine whether oral rucaparib is effective in the treatment of patients with locally advanced or metastatic pancreatic cancer and a known deleterious BRCA mutation.

Detailed description: Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) that inhibits a specific DNA repair pathway known as base excision repair (BER). PARP inhibitors (PARPi) have been shown to effectively kill tumors with a defect in BRCA1 or BRCA2. Clinical benefit has been observed in patients with a gBRCA mutation as well as in those with a somatic BRCA (sBRCA) mutation. Clinical data have also shown that pancreatic cancer patients with a gBRCA mutation benefit from PARPi treatment. Clinical activity of PARP inhibitors in BRCA-mutated pancreatic cancer combined with the paucity of 2nd line therapies support evaluation of rucaparib in pancreatic cancer patients known to harbor a deleterious BRCA mutation.

Eligibility: Inclusion Criteria:
  -  Confirmed diagnosis of pancreatic cancer (ductal adenocarcinoma and related subtypes eligible; endocrine and neuroendocrine tumors excluded)
  -  Received at least 1, but no more than 2, chemotherapy-based regimens for locally advanced or metastatic disease and has relapsed or progressive disease. Patients no longer able to continue treatment with chemotherapy due to intolerable toxicity may be considered for study participation provided that radiology assessment confirms either stable disease or disease progression (i.e. no response to treatment)
  -  Documented deleterious or suspected deleterious (or equivalent interpretation) BRCA mutation (germline or somatic) as assessed by a local laboratory
  -  Measurable disease
  Exclusion Criteria:
  -  Presence of another active cancer
  -  Prior treatment with any PARP inhibitor, including rucaparib. Patients treated with prior iniparib are eligible.
  -  Symptomatic and/or untreated central nervous system metastases.
  -  Clinical evidence of malabsorption and/or any other gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with the absorption of rucaparib.

Relevance to patient case: not relevant