araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: Relationship of pAKT to Survival in Patients With Node-Positive Breast Cancer

Summary: This study will examine the relationship of a protein called pAKT to survival of breast cancer patients with one or more positive axillary lymph nodes. Akt plays a role in cell survival, tumor formation, and the development of drug resistance.
  The study will use tumor tissue obtained from 2,000 patients enrolled in a National Surgical Adjuvant Breast and Bowel Project study that is evaluating whether adding the drug paclitaxel (Taxol (Registered Trademark)) to a treatment regimen of doxorubicin (Adriamycin (Registered Trademark)) and cyclophosphamide (Cytoxan (Registered Trademark)) improves disease-free survival and overall survival in patients with node-positive breast cancer. The current study will measure levels of pAkt in the tissues and correlate the results with clinical outcome to see if pAkt levels are associated with improved patient survival.

Detailed description: Taxanes (paclitaxel and docetaxel) have emerged as the most powerful chemotherapeutics in breast cancer over the past decades. The B-28 clinical trial from the National Surgical Adjuvant Breast and Bowel Project (NSABP) assesses the efficacy of adding paclitaxel to the doxorubicin/cyclophosphamide regimen in the treatment of patients with axillary node positive breast cancer. The primary aim of B-28 is to determine whether four cycles of paclitaxel (Taxol (Registered Trademark)) (T) following four cycles of postoperative Doxorubicin (adriamycin (Registered Trademark) (A) and cyclophosphamide (C) will more effectively prolong disease-free survival (DFS) and survival (S) than four cycles of AC alone in patients with operable breast cancer who have one or more histologically positive axillary lymph nodes. The B-28 clinical trial tissue microarray consists of specimens from 2,000 cases enrolled. The tissue microarray set is an ideal platform for evaluating predictive markers of doxorubicin and/or paclitaxel response or resistance.
  Akt, a serine/threonine protein kinase regulated by the phosphatidylinositol 3-kinase (PI3K), is of importance in cell survival, tumorigenesis, and recently shown, chemoresistance. It confers survival advantage to cells by transducing signals from growth factor receptors that activate PI3K. The primary aim of this study is to evaluate whether the levels of phosphorylated AKT are associated with disease-free and overall survival in patients with node-positive breast cancer treated with AC and/or AC followed by paclitaxel.

Eligibility: -  INCLUSION CRITERIA
  The NSABP B-28 trial enrolled women from 1995 to 1998 with operable breast cancer with pathologically positive axillary lymph nodes.

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: Ultraviolet Light Exposure and Immunosuppression in Cutaneous Melanoma

Summary: This project seeks to understand differences in the serum vitamin D levels and immune status in cutaneous malignant melanoma patients with different UV exposure histories in New Mexico.

Detailed description: It is well established that ultraviolet radiation (UV) exposure is related to the development of melanoma. There is also evidence that immune reactions are altered after UV exposure in the skin (locally) and perhaps throughout the body (systemically). Additionally, while the role of vitamin D and melanoma development has not been fully established, UV-B exposure is essential for vitamin D production in the skin. Increased sun exposure is also related to the presence of solar elastosis, which might protect (1) or improve survival from melanoma. Thus, melanoma represents a unique model for studying UV exposure, the immune system, and vitamin D. Malignant melanoma is an antigenic cancer; therefore, the role of UV exposure-induced immunosuppression and vitamin D production in the recognition, destruction and growth inhibition of cancerous melanocytes is worth further study.
  To underscore the importance of this project, the Scientific Advisory Committee of the Melanoma Research Foundation and the Steering Committee of the Society of Melanoma Research have indicated a need to collect more human data on the host immune response mechanisms in melanoma and also to focus on the skin as a whole microenvironment, moving away from only in vitro experiments.

Eligibility: Inclusion Criteria:
  -  Resident of New Mexico
  -  Age between the 1 and 95
  -  Newly diagnosed with cutaneous invasive melanoma; any stage permitted (ICDO C44.0-9) between September 1, 2008 and December 31, 2011.
  -  SSM (superficial spreading melanoma) and NM (nodular melanoma) histological subtypes are allowed
  -  Access to a telephone or be able to participate in a personal interview at the clinic
  -  Physically and mentally competent to complete a 1-hour telephone or personal interview
  Exclusion Criteria:
  -  Ocular melanoma, LMM (lentigo maligna melanoma) or ALM (acral lentigo melanoma), and mucosal melanoma cases.
  -  No access to a telephone or is not able to meet with the interviewer.

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: A Pharmacokinetic Study of RO5185426 in Combination With a Drug Cocktail in Patients With Metastatic Melanoma

Summary: This open-label single-arm study will evaluate the effect of RO5185426 [RG7204; PLEXXIKON: PLX4032] on the pharmacokinetics of five CYP450 substrates (caffeine, warfarin + vitamin K, omeprazole, dextromethorphan, midazolam) administered as a drug cocktail to patients with metastatic melanoma. The study will also evaluate efficacy and safety of RO5185426. On day 1, patients will receive the drug cocktail. On days 6 to 19, patients will receive RO5185426 twice daily. On day 20, patients will receive RO5185426 and the drug cocktail and on days 21 to 25, patients will receive RO5185426. Assessments will be made at regular intervals during the dosing periods and at follow-up. Patients may continue on study treatment (RO5185426) until the development of progressive disease or unacceptable toxicity. Target sample size <50.


Eligibility: Inclusion Criteria:
  -  Adult patient >/= 18 years of age
  -  Malignant melanoma (Stage IV, AJCC)
  -  Patients who are treatment-naive or have received prior systemic treatments for metastatic melanoma. Time elapsed between previous treatment for metastatic disease and first administration of study drug must be at least 28 days
  -  Positive tested for BRAF mutation
  -  Patients must not be poor metabolizers of CYP450 enzymes 2C9, 2C19, or 2D6 as determined by genotyping
  -  Measurable disease by RECIST criteria
  -  Negative pregnancy test; for fertile men and women, effective contraception during treatment and for 6 months after completion
  Exclusion Criteria:
  -  Active CNS lesions on CT/MRI within 28 days prior to enrollment
  -  History of known spinal cord compression, or carcinomatous meningitis
  -  Severe cardiovascular disease within 6 months prior to study

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: Measuring Real Time Decision-Making About Ultraviolet Radiation (UVR) Protection

Summary: The purpose of this study is to understand how people make decisions about sun protection. This study is important in helping to protect against sun exposure, since it is a main risk factor for melanoma. The investigators would like to understand the decisions people make about sun protection so that they can improve their ability to help individuals who may be at risk for melanoma.


Eligibility: Inclusion Criteria:
  -  A first-degree biological relative (a child, sibling or parent) as per self report of an MSKCC follow-up surgical patient diagnosed with melanoma as per pathology report or clinician's judgment;
  -  English-fluent; the surveys were designed and validated in English and are not currently available in other languages. Translation of questionnaires into other languages would require reestablishing the reliability and validity of these measures. Therefore, participants must be able to communicate in English to complete the surveys.
  -  18 years of age or older;
  -  For Phase I only: FDRs who live within a 50 mile radius of MSKCC to make it feasible for Ms. Shuk to be able to arrive at each person's home for the in-home interview without the cost being prohibitive;
  -  For Phase I only: Can recall a period when s/he was out in the sun for at least one hour on a sunny day this past summer 2009.
  -  For Phase I only: Can recall a separate period when s/he was out in the sun for at least one hour on a sunny day this past summer 2009, but s/he was in a different location from the period referenced above.
  -  For Phase II only: FDRs who self-report at least 1 consecutive hour in the morning (dawn to 12:30pm) and 1 consecutive hour in the afternoon (12:30-5pm) of daily (weekend and weekday) outdoor activities on the screening questionnaire
  Exclusion Criteria:
  -  First-degree relatives of melanoma patients who report never using UVR protection;
  -  Patient's who provide consent for Phase I will not be eligible for Phase II.
  -  Any first-degree relative of a melanoma patient who already has a first-degree relative who consented to the study;
  -  Unable to provide informed consent.

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: A Study of Vemurafenib (RO5185426) in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma (BRIM 3)

Summary: This randomized, open-label study evaluated the efficacy, safety and tolerability of vemurafenib (RO5185426) as compared to dacarbazine in previously untreated patients with metastatic melanoma. Patients were randomized to receive either vemurafenib 960 mg orally twice daily or dacarbazine 1000 mg/m2 intravenously every 3 weeks. Study treatment was continued until disease progression or unacceptable toxicity occurred. The data and safety monitoring board recommended that patients in the dacarbazine group be allowed to cross over to receive vemurafenib, and the protocol was amended accordingly on January 14, 2011, as both overall survival and progression-free survival endpoints had met the prespecified criteria for statistical significance in favor of vemurafenib.


Eligibility: Inclusion Criteria:
  -  adults, >/=18 years of age
  -  metastatic melanoma, stage IIIC or IV (AJCC)
  -  treatment-naïve (no prior systemic anticancer therapy)
  -  positive for BRAF V600E mutation
  -  measurable disease by RECIST criteria
  -  negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion
  Exclusion Criteria:
  -  active central nervous system metastases
  -  history of carcinomatous meningitis
  -  severe cardiovascular disease within 6 months prior to study drug administration
  -  previous malignancy within 5 years prior to study, except for basal or squamous cell carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: Survey Study - Sensitivity Comparison Between MelaFind and Physician Group

Summary: This survey study purposes to determine and compare the biopsy/referral sensitivity and specificity of MelaFind to the average biopsy/referral sensitivity and specificity of dermatologists. 241 subjects logged into system but only 183 signed consents and completed the intake survey. Out of these 183, 155 were accounted for in the data analysis after exclusions were removed from the pool of subjects.

Detailed description: Early detection of melanoma is critical for favorable prognosis, since patients with earlier stage melanomas have a much higher probability of survival than with later stages. The traditional method of early detection has been with serial total body skin exams where the health care provider examines all skin surfaces, including mucosa, for suspicious pigmented lesions. Studies have demonstrated that the diagnostic accuracy of physicians for melanoma depends on the level of dermatological training. More important than being able to make a diagnosis of melanoma on clinical impression is the ability to make an appropriate decision to biopsy the lesion. Primary care physicians (PCPs) are often expected to screen for melanoma and only refer to dermatologists when there is a high clinical suspicion of melanoma. However, if PCPs are not adept at diagnosing melanoma, then opportunities for early diagnosis and treatment could be missed. Conversely, the morphology of benign pigmented lesions can often mimic that of early melanomas, resulting in potentially unnecessary dermatology referrals, biopsies, and patient anxiety. Studies have indicated that there is great variability in the ability of PCPs to make a correct decision to biopsy/refer a pigmented lesion (1.5 times greater than dermatologists) as well as for diagnosing melanoma (over 2.5 times greater than dermatologists). To aid in detection of early melanomas, new technologies are being developed.
  One such technology is MelaFind, an investigational device that has been developed to give a recommendation for biopsy (or not) of pigmented skin lesions to rule out melanoma. Our hypothesis is that MelaFind will have equal or better sensitivity than pigmented lesion experts in making an appropriate recommendation for biopsy (i.e., MelaFind will be at least as accurate as dermatologists in recommending biopsy for melanomas).

Eligibility: Inclusion Criteria:
  -  Board Certified physicians or equivalent
  Exclusion Criteria:
  -  Did not participate in EOS Protocols 20061 or 20081

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: Study to Determine the Effectiveness of GSK1120212 in BRAF Mutation-positive Melanoma Previously Treated With or Without a BRAF Inhibitor

Summary: MEK113583 is a Phase II open-label, multi-site study to investigate the objective response rate, safety, and pharmacokinetics of GSK1120212 in subjects with BRAF mutation-positive melanoma who were previously treated with or without a BRAF inhibitor. GSK1120212 is a potent and highly selective inhibitor of MEK activation and kinase activity.


Eligibility: Inclusion Criteria:
  -  Metastatic cutaneous melanoma that was previously treated with: (Cohort A) a BRAF inhibitor either with or without other prior therapy. (Cohort B) at least 1 prior chemotherapy or immunotherapy, without treatment with a BRAF inhibitor.
  -  Documented positive BRAF mutation (V600E, V600K, or V600D).
  -  Subjects must provide archived tumor tissue or undergo fresh tumor biopsy prior to enrollment.
  -  The subject must have a radiographically measurable tumor.
  -  The subject is able to carry out daily life activities without significant difficulty (ECOG performance status score of 0 or 1).
  -  Able to swallow and retain oral medication.
  -  Sexually active subjects must use acceptable methods of contraception during the course of the study.
  -  Adequate organ system function and blood cell counts.
  Exclusion Criteria:
  -  The subject has had major surgery or received certain types of cancer therapy within 21 days before starting the study.
  -  Previous treatment with a MEK inhibitor.
  -  Current use of a prohibited medication listed in the protocol.
  -  Uncontrolled glaucoma.
  -  Brain metastasis, unless previously treated with surgery or stereotactic radiosurgery, and the disease has been stable for at least 2 months prior to enrollment.
  -  Current severe or uncontrolled systemic disease.
  -  History of clinically significant heart, lung, or eye/vision problems.
  -  Significant unresolved side effects from previous anti-cancer therapy.
  -  The subject is pregnant or breastfeeding.

Relevance to patient case: definitely relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: A Study of Avastin (Bevacizumab) in Combination With Fotemustine in Patients With Metastatic Melanoma

Summary: This study will investigate the efficacy and safety of bevacizumab + fotemustine in patients with stage IV melanoma, previously untreated with chemo- or immunotherapy for metastatic disease. Patients will receive Avastin (15mg/kg intravenously[IV]) on Day 1 of every 3 week cycle, in combination with fotemustine (100mg/m² IV) on Days 1, 8 and 15, followed by 4 weeks rest, followed by 100mg/m² IV every 3 weeks for 4-6 cycles. The anticipated time on study treatment is until disease progression, and the target sample size is <100 individuals.


Eligibility: Inclusion Criteria:
  -  cutaneous malignant melanoma;
  -  advanced, inoperable stage IV melanoma;
  -  measurable and/or evaluable sites of metastases.
  Exclusion Criteria:
  -  prior chemotherapy and/or IFN/IL2 based immunotherapy for metastatic disease;
  -  prior malignancies within past 5 years, with the exception of cured non-melanoma skin cancer, or in situ cancer of cervix;
  -  clinically significant cardiovascular disease;
  -  ongoing treatment with aspirin (>325mg/day) or other medications known to predispose to gastrointestinal ulceration.

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: Tesetaxel as Second-line Therapy for Patients With Advanced Melanoma and Normal Serum LDH

Summary: Tesetaxel is an orally administered chemotherapy agent of the taxane class. This study is being undertaken to evaluate the efficacy and safety of tesetaxel administered as second-line therapy to patients with advanced melanoma and normal serum lactate dehydrogenase (LDH).


Eligibility: Primary inclusion criteria:
  -  Histologically confirmed diagnosis of melanoma
  -  Progressive disease that is not surgically resectable, or metastatic Stage IV disease
  -  Measurable disease (revised RECIST; Version 1.1)
  -  Serum LDH not more than 1.1 times the upper limit of normal
  -  Eastern Cooperative Oncology Group performance status 0 or 1
  -  Treatment with 1 prior regimen (including cytotoxic chemotherapy, immunotherapy, radiation therapy, or cytokine, biologic, or vaccine therapy) as first-line treatment for metastatic disease (Administration of interleukin-2 or interferon as adjuvant therapy is allowed and is not to be considered in determining the 1 prior treatment regimen administered as first-line treatment for metastatic disease.)
  -  Adequate bone marrow, hepatic, and renal function, as specified in the protocol
  -  At least 3 weeks and recovery from effects of prior surgery or other therapy with an approved or investigational agent
  -  Ability to swallow an oral solid-dosage form of medication
  Primary exclusion criteria:
  -  History or presence of brain metastasis or leptomeningeal disease
  -  Primary ocular or mucosal melanoma
  -  Significant medical disease other than cancer
  -  Organ allograft
  -  Presence of neuropathy > Grade 1 (National Cancer Institute Common Toxicity Criteria [NCI CTC]; Version 4.0)
  -  Prior treatment with a taxane or other tubulin-targeted agent (eg, indibulin) other than a vinca alkaloid
  -  Need to continue any regularly-taken medication that is a potent inhibitor or inducer of the CYP3A pathway or P-glycoprotein activity

Relevance to patient case: not relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma

Summary: This open-label study will assess the pharmacokinetics, efficacy and safety of RO5185426 administered as 240mg tablets in previously treated patients with metastatic melanoma. Patients will be randomized to receive one of four dose-levels of RO5185426 [RG7204; PLEXXIKON; PLX4032] orally twice daily on days 1 to 15 (morning dose). Starting on day 22, treatment with RO5185426 may be resumed at a dose of 960 mg twice daily and continued until disease progression. Target sample size is <100 patients.


Eligibility: Inclusion Criteria:
  -  adult patients, >/=18 years of age
  -  histologically confirmed metastatic melanoma, stage IIIc or IV (AJCC)
  -  failure of at least one prior standard of care regimen
  -  positive for BRAF V600E mutation (by Roche CoDx BRAF mutation assay)
  -  ECOG performance status 0 or 1
  -  adequate hematologic, renal and liver function
  Exclusion Criteria:
  -  active CNS lesions on CT/MRI within 28 days prior to enrollment
  -  history of spinal cord compression o carcinomatous meningitis
  -  anticipated or ongoing anti-cancer therapies other than those administered in this study
  -  previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
  -  severe cardiovascular disease within 6 months prior to study
  -  previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix

Relevance to patient case: definitely relevant
Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: Biomarkers in Tissue and Blood Samples From Patients With Early-Stage Non-Small Cell Lung Cancer

Summary: RATIONALE: Studying samples of blood and tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.
  PURPOSE: This research study is studying biomarkers in tissue and blood samples from patients with early-stage non-small cell lung cancer.

Detailed description: OBJECTIVES:
  -  Evaluate aberrant methylation patterns in tissue and serum samples from patients with early-stage non-small cell lung cancer (NSCLC) to validate the Johns Hopkins single institutional study.
  -  Attempt to define subgroups of patients at greater risk for recurrent or metastatic disease who may benefit from more aggressive adjuvant therapeutic regimens.
  -  Develop prognostic indicators for disease-specific and overall survival.
  -  Define new potential molecular targets for therapy.
  OUTLINE: Archived tumor and intrathoracic lymph node tissue samples are analyzed for aberrant DNA methylation (p16/CDKN2A, DAP kinase, H-cadherin, APC, and RASSF1A) by methylation-specific PCR. Analyses are then compared with the preliminary data from the Johns Hopkins institutional study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Diagnosis of early-stage non-small cell lung cancer
  -  T1 or T2, N0 disease
  -  Had a lobectomy or greater resection with negative surgical margins (R0 resection)
  -  Available tumor and lymph node specimens from patients enrolled on ACOSOG-Z0040 and ACOSOG-Z0030 trials
  -  Node-negative with recurrent disease within 3 years (cases)
  -  Node-negative patients without recurrent disease (controls)
  PRIOR CONCURRENT THERAPY:
  -  See Disease Characteristics

Relevance to patient case: not relevant