araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: A Phase I Dose Escalation Study of CGM097 in Adult Patients With Selected Advanced Solid Tumors

Summary: This is a first in human phase I study of single agent CGM097 in patients with advanced solid tumors who have progressed despite standard therapy or for whom no standard therapy exists. The tumor must be characterized by p53wt status. The study consists of a dose escalation part where patients will receive escalating doses of CGM097, and a dose expansion part in which patients are given CGM097 at the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D). Each dose escalation step will be decided based on the recommendation from an adaptive Bayesian logistic regression model (BLRM).

Detailed description: This is a multi-center, open-label, dose finding, phase I study of single agent CGM097, administered in patients with advanced solid tumors who have progressed despite standard therapy or for whom no standard therapy exists. Patients' tumors must be characterized by p53wt status.
  The study consists of a dose escalation part, where cohorts of three to six newly enrolled patients will receive escalating doses of CGM097, and a dose expansion part, in which patients are given CGM097 the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D). Novartis and the site investigators will jointly decide on each dose escalation step based on the recommendation from an adaptive Bayesian logistic regression model (BLRM). If safety data should indicate a lower increment than suggested by the BLRM, the next dose level (DL) will be adjusted accordingly.

Eligibility: Inclusion Criteria:
  -  Patient has advanced solid malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
  -  Tumor of the patient is p53wt
  -  Evaluable disease as determined by RECIST 1.1
  -  WHO performance status 0-2
  Exclusion criteria:
  -  Prior treatment with CGM097 or other p53/HDM2-interaction inhibitor
  -  Patient with symptomatic or growing CNS metastatic lesions
  -  Concurrent other malignancy
  -  Clinically significant cardiac disease as defined in the protocol
  -  Diagnosis of acute or chronic pancreatitis
  -  Concomitant therapy that precludes enrollment, as defined in the protocol
  -  Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 2 weeks after study drug discontinuation
  -  Pregnant or nursing women
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: not relevant
Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

Summary: This randomized phase II trial studies how well psychosexual intervention works in patients with stage I-III gynecologic or breast cancer. Psychosexual intervention may improve sexual and psychosocial function.

Detailed description: PRIMARY OBJECTIVES:
  I. Efficacy for reducing the severity of sexual distress, difficulty, and dysfunction in a phase II randomized clinical trial (RCT).
  OUTLINE: Patients are randomized to 1 of 2 arms.
  ARM I (Enhanced standard care): Patients participate in enhanced standard care intervention comprising stress reduction, information delivery regarding gynecologic or breast cancer treatments and sexuality, and provision of a survivorship care plan (SCP) created using OncoLink over 1 hour following baseline assessment and before 6 months.
  ARM II (Psychological intervention): Patients participate in individual or group therapy over 1.5 hours weekly for 4 weeks, bi-weekly for 8 weeks, and monthly for 2 months and complete assessment interviews.
  After completion of study treatment, patients are followed up at 3, 6, and 9 months.

Eligibility: Inclusion Criteria:
  -  Stage I-III gynecologic (any site) or breast cancer
  -  Able to speak/read English
  -  Able to give informed consent
  Exclusion Criteria:
  -  Prior non-gynecologic/breast cancer diagnosis
  -  Refusal of any cancer treatment(s)
  -  Non-ambulatory
  -  Concurrent diagnosis of organic brain syndrome, dementia, mental retardation, or significant sensory deficit
  -  Major mental illness (e.g, schizophrenia, major depressive disorder)
  -  Current/recent (prior 12 months) pregnancy
  -  Residence > 70 miles from research site

Relevance to patient case: not relevant
Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: A Study of RO5503781 as a Single Agent or in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia

Summary: This Phase 1/1b, open-label study will evaluate the safety and pharmacokinetics of escalating doses of RO5503781 as a single agent or in combination with cytarabine in participants with acute myelogenous leukemia. In Part 1, RO5503781 will be administered in escalating doses as a single agent, and in Part 2, RO5503781 will be administered in combination with cytarabine. An optional Part 3 in which RO5503781 will be administered with cytarabine and anthracycline may be considered . In Part 4, the safety and pharmacokinetic profile of an optimized formulation of RO5503781 in combination with cytarabine will be assessed.


Eligibility: Inclusion Criteria:
  -  Documented/confirmed acute myelogenous leukemia (AML), except for acute promyelocytic leukemia
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 in Part 1 and Part 2, participants enrolled in the extension/tail portion, Part 3 and Part 4 must have an ECOG performance status of 0 or 1
  -  All non-hematological adverse events of any prior chemotherapy, surgery or radiotherapy must have resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade less than or equal to (</=) 2 prior to starting therapy
  -  Adequate hepatic and renal function
  -  Willing to submit the blood sampling and bone marrow sampling required by protocol
  Additional inclusion criteria for Parts 1-4 may apply.
  Exclusion Criteria:
  -  Participants receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 14 days of first receipt of study drug, with the exception of hydroxyurea as defined in protocol
  -  History of allergic or toxic reactions attributed to cytarabine (Part 2) or history of allergic reactions to components of the formulated product
  -  Current evidence of central nervous system (CNS) leukemia
  -  Participants with severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  -  Participants with evidence of electrolyte imbalance greater than or equal to (>/=) Grade 2 which cannot be corrected prior to study initiation
  -  Pregnant or breastfeeding women
  -  Human immunodeficiency virus (HIV) - positive participants receiving anti-retroviral therapy
  -  Participants who refuse to potentially receive blood products and/or have a hypersensitivity to blood products
  Additional exclusion criteria for Parts 1-4 may apply.

Relevance to patient case: not relevant
Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: Biomarker Differences in Samples From Patients With Undifferentiated Sarcomas

Summary: This clinical trial studies biomarker differences in samples from patients with undifferentiated sarcomas. Studying biomarker in tissue samples from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer

Detailed description: Study Subtype: Ancillary/Correlative Observational Study Model: Cohort Time Perspective: Prospective Biospecimen Retention: Samples With DNA Biospecimen Description: Tissue Study Population Description: Patients from ARST0332 study Sampling Method: Non-Probability Sample
  PRIMARY OBJECTIVES:
  I. To determine what proportion of unclassifiable sarcomas are unclassifiable because the initial evaluation was not sufficiently comprehensive versus what proportion can be regarded as "true" undifferentiated sarcoma when a comprehensive assessment has been performed.
  II. To develop formal diagnostic criteria for establishing the diagnosis of undifferentiated sarcoma.
  III. To determine whether undifferentiated sarcoma can be subdivided into separate and distinct pathologic entities that are distinguishable by light microscopy, immunohistochemistry, single nucleotide polymorphism (SNP) array profiling, or clinical features.
  IV. To determine whether undifferentiated sarcomas with specific "actionable mutations" can be identified based on their histologic appearance, immunohistochemical staining characteristics, or SNP array profiling features.
  OUTLINE:
  Tissue samples are analyzed for loss of heterozygosity (LOH) and SNP array profiling using microarray and immunohistochemistry.

Eligibility: Inclusion Criteria:
  -  49 cases of undifferentiated sarcomas from ARST0332 (additional cases may be ascertained as eligible for this current project that also fall under ARST0332 to be requested later if necessary)

Relevance to patient case: not relevant
Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: Autologous Dendritic Cell Vaccine Loaded With Allogeneic Tumor Lysate Expression of Cancer Testis Antigens in Patients With Soft Tissue Sarcoma

Summary: The purpose of this study is to achieving a six-month progression free survival (PFS) of patients receiving autologous dendritic cell vaccine (ADKV) loaded with allogeneic tumor lysate expression of cancer-testis antigens (CTA) in patients with soft tissue sarcomas


Eligibility: Inclusion Criteria:
  -  age of 18 or older
  -  ECOG performance score 0 or 1
  -  Histologically proven soft tissue sarcoma
  -  Unresectable or metastatic soft tissue sarcoma
  -  Ability to give written informed consent
  -  Objective measured and measurable tumor lesions
  -  The failure of standard therapy
  -  Adequate amount of material for genetic research
  -  No active or chronic infection with HIV, Hepatitis B or Hepatitis C
  -  Men/Women of childbearing potential must use adequate contraception
  -  Hematology, liver function and renal function lab tests within required parameters
  Exclusion Criteria:
  -  Untreated or uncontrolled brain metastases.
  -  History of other active malignancy within last 2 years, except adequately treated other soft tissue sarcoma.
  -  Autoimmune disease (vitiligo is not a basis for exclusion).
  -  Serious uncontrolled medical disorder or active infection that would impede treatment.
  -  Underlying medical or psychiatric condition that would cause administration vaccine
  -  Any non-oncology vaccine therapy up to 1 month before or after any dose of vaccine
  -  Concomitant therapy with IL-2, interferon, other non-study immunotherapy, or cytotoxic chemotherapy; immune-suppressive agents within 30 days of registration; other investigational therapies; chronic use of systemic corticosteroids (however, a low stable dose steroid for mild brain edema or adrenal insufficiency is allowed; topical and inhaled standard dose corticosteroids are allowed).
  -  Dementia or significantly altered mental status that would prohibit understanding or rendering of informed consent and compliance with protocol requirements.
  -  Pregnant or breastfeeding women.
  -  Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g. infectious) illness.

Relevance to patient case: not relevant
Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: CPCT-05 Biopsy Protocol Patient Selection

Summary: Our knowledge on the genetic mutations in cancer is rapidly expanding and we are increasingly testing drugs in mainly metastatic cancer patient populations with rare mutations. Successful examples of this new strategy are ALK inhibitors in ALK translocated NSCLC (less than 5% frequency) and EGFR inhibitors in EGFR mutant NSCLC (approximately 5% frequency). Selecting molecularly stratified patient populations for studies benefits the patient as it increases the odds of obtaining benefit from experimental treatment, especially in early clinical trials. Moreover it increases the speed and efficacy of drug development as signs of efficacy are picked up in earlier phases. Therefore, broad screening of molecular lesions in the tumors of patients that are being considered for participation in trials is crucial. This pre-selection increases our ability to perform several trials in parallel and thus include more patients in more meaningful trials. With the still dismal prognosis of patients with metastatic cancer, increasing the accrual rate to pivotal trials in selected patient populations is a key factor in improving prognosis.
  The advent of Next Generation Sequencing (NGS) platforms enables us to probe a limited number of cancer related genes within 2-4 weeks. We have extensively piloted this approach and are now able to deliver clinically meaningful turn-around-times. This development enables us to use this technology to enrich clinical trials using targeted therapies for patients with specific mutations.
  We will obtain tumor biopsies of a metastatic or locally advanced lesion and a peripheral blood sample from all patients included in the trial; the biopsies to obtain information on the tumor related genetic mutations (mutational profile) and the blood samples to assess each patient's germline DNA background variation. As patients will be asked to undergo an invasive procedure it is important to address the potential safety issues. Review of the literature and our own experience show that tumor biopsies can be performed with only minor complications and acceptable risks. We will recruit patients with metastatic or locally advanced solid tumors from patients that can potentially be included in clinical trials.


Eligibility: Inclusion Criteria:
  -  Locally advanced (incurable) or metastatic cancer from a histological or cytological proven solid tumor
  -  Indication for systemic treatment with anti-cancer agents (with no treatment options with curative intent)
  -  Measurable locally advanced (incurable) or metastatic lesion(s), according to RECIST 1.1 criteria.
  -  Safe biopsy of a metastatic or locally advanced lesion possible
  -  No contraindications for lidocaine (or its derivatives) and/or midazolam and/or phentanyl
  -  Adequate organ function
  -  WHO performance status 0-2
  -  Age > 18 yr
  -  Expected adequacy to follow up
  -  Written informed consent
  Exclusion Criteria:
  • If one or more of the above mentioned inclusion criteria is not met

Relevance to patient case: not relevant
Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: Tissue Banking Study - Polycythemia Vera or Essential Thrombocythemia (PV & ET) Patients

Summary: The purpose of the study is to isolate and characterize stem cells of patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) to find out why these cells are not working the way they should be and why they seem to be sensitive to regulatory factors in the blood, such as clotting.

Detailed description: Specific Aim 1: Assess the effects of RG7112 on MPN HSC/HPC p53 levels and study how it affects MPN stem cell function.
  Specific Aim 2. Assess the effects of a combination of low doses of IFNα and RG7112 on MPN HSC/HPC.

Eligibility: Inclusion Criteria:
  -  polycythemia vera or essential thrombocythemia
  -  agree to give blood for study
  Exclusion Criteria:

Relevance to patient case: not relevant
Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: A Study of MEHD7945A and Cobimetinib in Patients With Locally Advanced or Metastatic Cancers With Mutant KRAS

Summary: This open-label, multicenter, global Phase Ib study will evaluate the safety, tolerability and pharmacokinetics of intravenous (IV) dosing of MEHD7945A in combination with oral dosing of cobimetinib in patients with locally advanced or metastatic solid tumors that carry a Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutation and for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate. The study comprises a dose-escalation (Stage 1) and an indication-specific cohort expansion stage (Stage 2).


Eligibility: Inclusion Criteria:
  -  Locally advanced or metastatic solid KRAS-mutant tumors, for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  -  Evaluable disease or disease measurable per modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
  -  Consent to provide archival tumor tissue for biomarker testing
  -  Additionally, for patients who are considered for enrollment into the indication specific expansion cohorts in Stage 2, the current cancer must be either KRAS-mutant colorectal cancer (CRC) or KRAS-mutant non-small cell lung cancer (NSCLC)
  Exclusion Criteria:
  -  History of prior significant toxicity from another MEK pathway inhibitor or combination of another MEK and epidermal growth factor receptor (EGFR) inhibitor requiring discontinuation of treatment
  -  Previous treatment with a combination of a MEK inhibitor with an EGFR inhibitor (applies only to the indication specific expansion cohorts in Stage 2)
  -  Allergy or hypersensitivity to components of the cobimetinib formulations
  -  History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of therapy
  -  History of interstitial lung disease (ILD)
  -  Known severe ulcer disease
  -  History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioetinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
  Patients will be excluded if they currently have either of the following conditions which have been identified as risk factors for CSCR:
  -  Uncontrolled glaucoma with intraocular pressure greater than (>) 21 millimeters of mercury (mm Hg)
  -  Grade greater than equal to (>=) 3 hypertriglyceridemia

Relevance to patient case: not relevant
Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: A Phase 1b Study Evaluating AMG 232 Alone and in Combination With Trametinib in Acute Myeloid Leukemia

Summary: Open-label, sequential dose escalation and expansion study of AMG 232 in subjects with acute myeloid leukemia.


Eligibility: Inclusion Criteria:
  -  Men or women > 18 years old
  -  Pathologically-documented, definitively-diagnosed AML that is relapsed or refractory to standard treatment, for which no standard therapy is available or the subject refuses standard therapy
  -  Ability to take oral medications and willing to record daily adherance to investigational product
  -  Adequate hematological, renal, hepatic, and coagulation laboratory assessments
  Exclusion Criteria:
  -  Active infection requiring intravenous (IV) antibiotics
  -  Prior participation in an investigational study (procedure or device) within 21 days of study day 1
  -  Major surgery within 28 days of study day 1
  -  Anti-tumor therapy within 14 days of study day 1

Relevance to patient case: not relevant
Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma

Summary: Phase 1b/2a, open-label, sequential dose escalation and expansion study of AMG 232 in combination with trametinib and dabrafenib in subjects with metastatic melanoma followed by a direct comparison of AMG 232 combined with trametinib and dabrafenib versus trametinib combined with dabrafenib alone.

Detailed description: The study will be conducted in 3 parts: Part 1 - Dose Escalation, Part 2 - Dose Expansion and Part 3, a randomized Phase 2a.
  In both part 1 and 2, subjects will be enrolled open-label into 1 of 2 arms. For both Arm 1 and Arm 2, the part 1 dose escalation is aimed at determining an AMG 232 maximum tolerated dose (MTD) with a fixed dose of the combination drug(s) and evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of each combination. Part 2 dose expansion will enroll subjects to receive therapy with a dose and schedule of AMG 232 selected from the corresponding part 1 dose escalation. In part 2 subjects will be enrolled to confirm safety and tolerability and to assess clinical activity prior to proceeding to Part 3, Phase 2a. In Phase 2a, Subjects will be randomized open-label in a 1:1 ratio to receive AMG 232 in combination with trametinib plus dabrafenib versus trametinib plus dabrafenib alone.

Eligibility: Inclusion Criteria: Subjects must have histologically or cytologically confirmed metastatic cutaneous or mucosal melanoma, Able to swallow and retain orally administered medication, Adequate hematological, renal, hepatic, and coagulation laboratory assessments Exclusion Criteria: Clinically significant bleeding within 4 weeks of screening, Current use of warfarin, factor Xa inhibitors, and direct thrombin inhibitors, Infection requiring anti-infective treatments within 1 week of study enrollment, Anti-tumor therapy, Major surgery within 28 days

Relevance to patient case: not relevant
Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: Pazopanib for Metastatic Alveolar Soft Part Sarcoma

Summary: Alveolar soft part sarcoma (ASPS), a rare subset of STS (<1%) harbors t(X;17)(p11;q25) translocation and produces resultant ASPL-TFE3 fusion protein. Due to its nature of high expression of angiogenic factors, sunitinib and cediranib produced overall response rates of 55% and 43%, respectively. However, the efficacy of pazopanib is unknown in metastatic ASPS.

Detailed description: Pazopanib, a multi-targeted anti-angiogenesis inhibitor significantly prolonged progression-free survival (PFS) in patients with metastatic soft-tissue sarcoma (STS) after failure to anthracycline-based regimen (pazopanib vs placebo, 4.6 vs 1.6 months, HR=0.31, 95% CI 0.24-0.40; P < .0001). Regarding sunitinib (continuous daily dose of 37.5mg), after a median duration of 10 months, median OS and PFS were 19 months and 17 months, respectively in a small retrospective study (ASPS, N=9). With regard to cediranib, 6-month PFS was over 60%. In addition, randomized phase II trial of sunitinib vs cediranib with cross-over at disease progression was recently initiated (NCT01391962). However, the efficacy of pazopanib is unknown in metastatic ASPS.

Eligibility: Key Inclusion Criteria:
  -  Histologically confirmed diagnosis of alveolar soft part sarcoma harboring TFE3 fusion at stage IV or at relapse
  -  Age ≥ 18 years
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  -  Measurable lesion defined by RECIST v1.1
  -  Chemo-naïve or prior chemotherapies
  -  Adequate organ function
  Exclusion Criteria:
  -  Prior malignancies
  -  Active CNS disease
  -  High-risk for gastrointestinal bleeding
  -  Significant cardiovascular disease
  -  Uncontrolled hypertension
  -  Bleeding diathesis

Relevance to patient case: not relevant