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315 Study Matches

Testing the Use of Fulvestrant and Binimetinib Targeted Treatment for NF1 Mutation in Hormone Receptor-Positive Metastatic Breast Cancer, A ComboMATCH Treatment Trial

This ComboMATCH phase II trial compares the usual treatment alone (fulvestrant) to using binimetinib plus the usual treatment in patients with hormone receptor positive breast cancer that has spread from where it first started to other places in the body (metastatic) and has an NF1 genetic change. Fulvestrant is a hormonal therapy that binds to estrogen receptors in tumor cells, resulting in estrogen receptor destruction and decreased estrogen binding, which may inhibit the growth of estrogen-sensitive tumor cells. Binimetinib is a targeted therapy that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of binimetinib to fulvestrant in breast cancers with an NF1 genetic change could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression) as compared to fulvestrant alone.
Mark Burkard, MD, PhD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05554354
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Inclusion Criteria:

• A COMBOMATCH TREATMENT TRIAL EAY191 ELIGIBILITY CRITERIA:
• The patient must be enrolled on the ComboMATCH Master Registration Trial EAY191
• Note: Patients must fulfill all eligibility criteria outlined in the ComboMATCH Registration Trial EAY191 at the time of registration to EAY191-N2. This includes submission of next-generation sequencing (NGS) data from one of the National Cancer Institute (NCI) credentialed designated laboratories for all potential patients prior to treatment trial assignment. Copy number and allele frequency cutoff as per the Registration protocol
• Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or, if disease cannot be safely biopsied, have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH registration trial (EAY191)
• Please note the current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trial Support Unit (CTSU) ComboMATCH Registration protocol page
• Please note novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH Registration protocol
• A COMBOMATCH TREATMENT TRIAL EAY191-N2 ELIGIBILITY CRITERIA:
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 within 14 days prior to registration
• Histologically or cytologically confirmed invasive breast carcinoma
• Confirmed metastatic disease by either imaging or tissue diagnosis
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and one additional lesion that can be biopsied (primary, metastatic both allowed)
• Patients must have NF1 nonsense or frameshift mutation, or NF1 whole gene deletion detected in tumor as determined by the ComboMATCH screening assessment
• The tumor must have been determined to be estrogen receptor (ER) and/or progesterone receptor (PgR) positive assessed by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone receptor testing. Patients with >= 1% ER or PgR staining by immunohistochemistry (IHC) are considered positive
• The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines
• Prior use of CDK4/6 inhibitor(i) is required
• Prior use of fulvestrant regardless of duration is allowed and will determine treatment assignment
• Up to one line of chemotherapy in metastatic setting is allowed
• Absolute neutrophil count >= 1,500/mm^3 (within 14 days prior to registration)
• Platelet count >= 100,000/ mm^3 (within 14 days prior to registration)
• Hemoglobin level >= 10 g/dL (within 14 days prior to registration)
• Measured or calculated creatinine clearance > 30 mL/min (within 14 days prior to registration)
• Total bilirubin level =< institutional upper limit of normal (within 14 days prior to registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =< 5.0 x ULN
• Left ventricular ejection fraction (LVEF) assessment must be performed within 6 weeks prior to registration (LVEF assessment performed by echocardiogram is preferred; however, multi-gated acquisition scan [MUGA] scan may be substituted based on institutional/situational preferences). The LVEF must be >= 50% regardless of the cardiac imaging facility's lower limit of normal
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
• ELIGIBILITY CRITERIA FOR COHORT 1, TREATMENT REGIMEN 2 PATIENTS WHO TRANSITION TO COHORT 2:
• Patient's willingness to transition to Cohort 2 affirmed
• The patient must have an ECOG performance status of 0-2
• Absolute neutrophil count >= 1,500/mm^3 (within 14 days prior to second registration)
• Platelet count >= 100,000/ mm^3 (within 14 days prior to second registration)
• Hemoglobin level >= 10 g/dL (within 14 days prior to second registration)
• Total bilirubin level =< institutional upper limit of normal (ULN) (within 14 days prior to second registration)
• AST and ALT must be =< 5.0 x ULN
• Measured or calculated creatinine clearance > 30 mL/min (within 14 days prior to second registration)
• The LVEF performed within the last 3 months must be >= 50% regardless of the cardiac imaging facility's lower limit of normal (LVEF assessment performed by echocardiogram is preferred; however, MUGA scan may be substituted based on institutional/situational preferences)
• Pregnancy test according to institutional standards done within 14 days before second registration must be negative (for patients of childbearing potential only)
Exclusion Criteria:

• Concurrent anticancer therapy
• Active autoimmune disease requiring systemic treatment within the past 3 months, documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
• Active brain metastasis. Brain metastases that have been stable for at least 1 month after completion of treatment are not an exclusion criterion
• History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous, chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
• Patients will be excluded if they currently have the following risk factors for RVO that are documented prior to the enrollment:
• Uncontrolled glaucoma with intra-ocular pressures >= 21 mmHg
• Serum cholesterol >= grade 2.
• Hypertriglyceridemia >= grade 2
• Hyperglycemia (fasting) >= grade 2
• Patients with baseline QT corrected for heart rate (QTc) > 500 ms, either induced by medication or congenital long QT syndrome will be excluded due to known side effects of binimetinib
• Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) >= grade 2 within 14 days prior to registration. Patients with nervous system disorders that resolve to =< Grade 1 prior to registration are eligible
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results
• Pregnancy or lactation at the time of registration or intention to become pregnant during the study (Note: Pregnancy testing according to institutional standards for patients of childbearing potential must be performed within 14 days prior to registration)
• For binimetinib, highly effective contraception should be used for at least 30 days after the last dose, and patients should not breastfeed for 3 days after the last dose
• For fulvestrant, highly effective contraception should be used for 1 year after the last dose, and patients should not breastfeed for 1 year after the last dose
• Use of any investigational product within 30 days prior to study entry
• INELIGIBILITY CRITERIA FOR COHORT 1, TREATMENT REGIMEN 2 PATIENTS WHO TRANSITION TO COHORT 2
• Not a candidate for binimetinib in the opinion of the treating investigator
Breast, Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Negative Breast Carcinoma, Metastatic Hormone Receptor-Positive Breast Carcinoma
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Study of EO-3021 in Adult Patients With Solid Tumors Likely to Express CLDN18.2

This study is an open-label, international, multi-center, Phase 1 study in adult patients with solid tumors likely to express CLDN18.2.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05980416
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Key
Inclusion Criteria:

• Availability of tumor tissue (archived and fresh tumor biopsy, if medically feasible)
• Select advanced or metastatic solid tumor that is likely to express CLDN18.2 such as gastric/GEJ, pancreatic and esophageal cancer
• ≥ 18 years of age
• ECOG performance status (PS) 0 or 1 at Screening
• Progressed on or after standard therapy, or are intolerable for available standard therapy, or there is no available standard therapy
• Have at least one measurable extra-cranial lesion as defined by RECIST v1.1
• Adequate organ function
• Life expectancy > 12 weeks
• Ability to understand the nature of this study, comply with protocol requirements, and give written informed consent
• Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following study completion Key
Exclusion Criteria:

• Pregnant or breastfeeding
• Symptomatic or untreated brain metastases
• Have previously received CLDN18.2 antibody drug conjugates (ADCs) or any ADC containing an auristatin payload (prior monoclonal antibody against CLDN18.2 may be eligible)
• Have peripheral neuropathy Grade ≥2
• Have history of non-infectious pneumonitis/interstitial lung disease
• Have diagnosis of another malignancy, or history of systemic treatment for invasive cancer within last 3 years. Note: Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. Diagnosis of non-melanoma skin cancer, carcinoma in situ of the cervix or breast, or noninvasive tumor does not affect eligibility
• Have active ocular surface disease at baseline (based on screening ophthalmic examination)
• Have serious concurrent illness or clinically relevant active bacterial, fungal or viral infection
• Have previous hypersensitivity to any known components of EO-3021 or history of severe infusion reaction or hypersensitivity (CTCAE Grade 3 or higher) with monoclonal antibody treatment
• Clinically significant cardiac disease, including but not limited to symptomatic congestive heart failure, unstable angina, acute myocardial infarction within 6 months of planned first dose, or unstable cardiac arrhythmia requiring therapy (including torsades de pointes)
• Have history of allogenic hematopoietic stem cell transplantation or solid organ transplantation with ongoing systemic immunosuppressive therapy
• Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the Investigator
Pancreas Neoplasm, Stomach Neoplasm, Gastrointestinal Neoplasms, Digestive System Neoplasm, Neoplasms by Site, Neoplasms, Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus
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A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010)

The purpose of this study is to assess the safety and tolerability and to confirm the dose of nemtabrutinib in combination with venetoclax in participants with R/R CLL/SLL. The primary study hypotheses are that the combination of nemtabrutinib plus venetoclax is superior to VR with respect to progression-free survival (PFS) per 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria as assessed by blinded independent central review (BICR).
Christopher Fletcher, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05947851
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Inclusion Criteria:

• Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and active disease clearly documented to initiate therapy.
• Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, immunoglobulin heavy chain gene (IGHV) mutation status and Bruton's tyrosine kinase (BTK)-C481 mutation status results required before randomization for Part 2 participants only.
• Relapsed or refractory to at least 1 prior available therapy.
• Have at least 1 marker of disease burden.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before randomization.
• Has a life expectancy of at least 3 months.
• Has the ability to swallow and retain oral medication.
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV deoxyribonucleic acid (DNA) viral load before randomization.
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV ribonucleic acid (RNA) viral load is undetectable at screening.
• Participants with human immunodeficiency virus (HIV) who meet ALL eligibility criteria.
• Participants with adequate organ function with specimens collected within 7 days before the start of study intervention.
• If capable of producing sperm, participant agrees to eliminate Nemtabrutinib: 12 days, Venetoclax: 1 month (30 days), Rituximab (rituximab biosimilar): not applicable; abstains from penile-vaginal intercourse as their preferred and usual lifestyle; OR uses prescribed contraception.
• Participant assigned female sex at birth are eligible to participate if not pregnant or breastfeeding and are not a person of childbearing potential (POCBP) OR is a POCBP and uses a contraceptive method that is highly effective, has a negative highly sensitive pregnancy test, and abstains from breastfeeding.
Exclusion Criteria:

• Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
• Has gastrointestinal (GI) dysfunction that may affect drug absorption.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL.
• Has an active infection requiring systemic therapy, such as intravenous (IV) antibiotics, during screening.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease and/or acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.
• Has QT interval corrected (QTc) prolongation or other significant electrocardiogram (ECG) abnormalities.
• Has a known allergy/sensitivity to nemtabrutinib or contraindication to venetoclax/rituximab (or rituximab biosimilar), or any of the excipients.
• Has history of severe bleeding disorders (eg, hemophilia).
• Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before randomization.
• Has received prior B-cell lymphoma 2 inhibitor(s) (BCL2i) including venetoclax or Non-covalent Bruton's tyrosine kinase inhibitor (BTKi).
• Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A strong inhibitors.
• Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention.
• Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
• Has a known psychiatric or substance use disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
• Participants who have not adequately recovered from major surgery or have ongoing surgical complications.
Lymphoid Leukemia, Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic, Small-Cell Lymphoma, Lymphoma, Small Lymphocytic, CLL, SLL
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Correlating Early FDG PET/CT and ctDNA in Immune Checkpoint Inhibitor (ICI)-Treated Melanoma Patients

The purpose of this research study is to determine if analysis of PET/CT scans and testing of blood samples in people with melanoma that has spread in their body can help researchers determine which patients are more or less likely to respond to immunotherapy and are more or less likely to have side effects. 24 participants will be enrolled and be on study until approximately 4 weeks after their first dose of Immune Checkpoint Inhibitor therapy.
Vincent Ma, MD
All
18 Years and over
IV
This study is NOT accepting healthy volunteers
NCT06199713
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Inclusion Criteria:

• Willing to provide informed consent.
• Must have a metastatic melanoma diagnosis (stage IV) for which treatment with ipilimumab, nivolumab, and/or pembrolizumab, either alone or in combination with other ICI therapy, is planned.
• Must be planning to participate in Signatera™ (ctDNA level) monitoring with standard of care laboratory testing routinely obtained for treatment with ICI therapy.
• Individuals at least 18 years of age.
• Women of childbearing potential must be willing to use effective contraception as discussed with their oncologist while participating in this study.
• Willing to comply with all study procedures and be available for the duration of the study.
Exclusion Criteria:

• Not able to receive treatment with ICI therapy
• Use of investigational drugs, biologics, or devices within 30 days prior to enrollment.
• Women who are pregnant, lactating, or planning on becoming pregnant during the study.
• Not suitable for study participation due to other reasons at the discretion of the investigators.
Melanoma, Melanoma Stage III, Melanoma Stage IV, Unresectable Melanoma, Melanoma, Skin, Other Skin, Melanoma/Skin cancer
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Transversus Abdominis Plane Block Compared to Local Anesthetic Wound Infiltration in Gynecologic Oncology Surgery

This study is being done to see if preoperative transversus abdominis plane (TAP) analgesia will provide similar postoperative pain control, hospital length of stay, and postoperative outcomes compared to surgeon-initiated wound infiltration with local anesthetic in participants undergoing laparotomy for gynecologic indications.
Sumer Wallace, M.D.
Female
18 Years and over
Phase 4
This study is NOT accepting healthy volunteers
NCT06213454
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Inclusion Criteria:

• Ability to understand and the willingness to sign a written informed consent document
• Patients undergoing exploratory laparotomy via midline vertical skin incision for gynecologic indications at UW Hospital and Clinics
• Patients must be >18 years old
• English speaking (able to provide consent and complete questionnaires)
• Patients must have the ability to understand visual and verbal pain scales
• Patients must be eligible for TAP block placement. This will be confirmed during preoperative visit with the primary surgeon. Patient's are not eligible if they have allergies to the anesthetic medications or have had prior abdominal reconstructive surgery that would alter their abdominal wall anatomy in a way where the block would not be expected to be effective.
Exclusion Criteria:

• Known allergy to local anesthetics.
• Known history of chronic pain disorders and/or chronic opioid use defined as greater than 10mg of PO morphine or equivalent used daily for at least 30 days prior to enrollment.
• Patient has a history of opioid dependence requiring rehabilitation or the use of opioid antagonists.
• Patients with a planned exploration with biopsies (no organs removed) will be excluded from the study.
• Individuals who are pregnant, lactating or planning on becoming pregnant during the study.
• Significant liver disease that would inhibit prescription of opioids.
• Significant kidney disease that would inhibit administration of gabapentin.
• Not suitable for study participation due to other reasons at the discretion of the investigators.
Analgesia, Surgery, Cervix, Corpus Uteri, Ovary, Other Female Genital, Uterus
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Tobacco Treatment Comparison for Cancer Care

This pilot comparative effectiveness trial will compare two active smoking cessation treatments in terms of effectiveness, equity across patient subpopulations, and efficiency among adult patients diagnosed with cancer within the past 3 years. An enhanced treatment comprising 12 weeks of varenicline treatment and 7 smoking cessation coaching calls with a cancer focus will be compared against an active comparator modeled after standard quitline treatments (2 weeks of nicotine patch therapy with 3 phone coaching calls). Approximately 50 participants will be recruited to generate estimates of the effects, acceptability, costs, and equity of enhanced treatment (vs. standard treatment), with the primary outcome being abstinence from smoking 26 weeks after trying to quit.
Danielle Mccarthy
All
18 Years and over
Phase 4
This study is NOT accepting healthy volunteers
NCT06218823
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Inclusion Criteria:

• Alive (per medical record)
• Diagnosed with cancer in the past 3 years
• Received care from a participating oncology clinic in the past year
• Has a current tobacco use status
• Does not have a preferred language other than English (missing language preference will be included).
• Valid address that is not a correctional facility or residential treatment/care facility.
• No flag for patient cognitive impairment, activated health care power of attorney, or other health care agent (e.g., legally authorized representative) in the EHR. The following additional inclusion criteria must be met for inclusion in the CET
• Smoked combustible cigarettes in the past month.
• Able to speak and understand English.
• Willing to set a date to quit smoking in the next 60 days.
• Willing to receive smoking treatment information.
• Willing to complete study activities.
Exclusion Criteria:

• No current suicidal ideation.
• Suicide attempt in the past year.
• Currently receiving treatment for bipolar disorder, schizophrenia, schizoaffective disorder, or psychotic disorder.
• Incarceration.
• Unable to provide informed consent to treatment (i.e., cannot answer questions about study procedures or risks after hearing about the study).
Smoking Cessation, Cancer, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
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A Study to Investigate the Safety and Efficacy of K-321 Eye Drops After Simultaneous Cataract Surgery and Descemetorhexis in Participants With Fuchs Endothelial Corneal Dystrophy (FECD)

A study to assess the safety and efficacy of K-321 in participants with FECD after simultaneous cataract surgery and descemetorhexis.
Evan Warner
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05826353
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Inclusion Criteria:

• Is at least 18 years old at the screening visit (Visit 1)
• Has a diagnosis of FECD at Visit 1
• Meet all other inclusion criteria outlined in the Clinical Study Protocol.
Exclusion Criteria:

• Is a female subject of childbearing potential and any of the following is true: 1. is pregnant or lactating/breastfeeding, or 2. is not surgically sterile, not post-menopausal (no menses for the previous 12 months), or not practicing an effective method of birth control as determined by the Investigator (eg, oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy)
• Meet any other exclusion criteria outlined in the Clinical Study Protocol.
Fuchs Endothelial Corneal Dystrophy, Other, Eye & Vision
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A Phase 1/2 Study of DCC-3116 in Patients With MAPK Pathway Mutant Solid Tumors

This is a Phase 1/2, multicenter, open label, first in human (FIH) study of DCC-3116 as monotherapy, and in combination with trametinib, binimetinib, or sotorasib in patients with advanced or metastatic solid tumors with RAS/MAPK pathway mutation. The study consists of 2 parts, a dose-escalation phase, and an expansion phase.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04892017
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Inclusion Criteria:
1. Male or female participants ≥18 years of age 2. Dose Escalation Phase (Part 1): 1. Participants must have a pathologically confirmed diagnosis of an advanced or metastatic solid tumor with a documented RAS, NF1, or RAF mutations. A molecular pathology report documenting mutational status of RAS, NF1, or RAF must be available. 2. Progressed despite standard therapies, and received at least 1 prior line of anticancer therapy.
• Participants with a documented mutation in BRAF V600E or V600K must have received approved treatments known to provide clinical benefit prior to study entry. 3. Participants enrolled in the DCC-3116 and sotorasib cohort (Cohort D) must have a KRAS G12C mutation. 3. Dose Expansion Phase (Part 2): 1. Cohort 1: Patients with Pancreatic Ductal Adenocarcinoma (PDAC).
• Pathologically confirmed PDAC with a documented mutation in KRAS.
• Received only 1 prior line of systemic therapy in the advanced or metastatic setting. 2. Cohort 2: Patients with Non-Small Cell Lung Cancer (NSCLC)
• Pathologically confirmed NSCLC with a documented mutation in KRAS, NRAS, NF1, or BRAF.
• Received at least 2 prior lines but no more than 4 prior lines of systemic therapy in the advanced or metastatic setting. 3. Cohort 3: Patients with Colorectal Cancer (CRC)
• Pathologically confirmed CRC with a documented mutation in KRAS, NRAS, NF1, or BRAF.
• Received at least 2 prior lines of systemic therapy in the advanced or metastatic setting. 4. Cohort 4: Patients with Melanoma
• Pathologically confirmed melanoma with a documented mutation in NRAS.
• Received at least 1 but not more than 2 prior lines of systemic therapy in the advanced or metastatic setting that included T-cell checkpoint inhibitor-based therapy.
• Have not received prior MEK inhibitor therapy. 5. Cohort 5: Patients with KRAS G12C mutant NSCLC
• Pathologically confirmed NSCLC with a documented mutation in KRAS G12C.
• Received at least 1 prior line but no more than 3 prior lines of systemic therapy in the advanced or metastatic setting.
• Have not received prior sotorasib or other KRAS G12C inhibitor therapy. 4. Must provide a fresh tumor biopsy from a primary or metastatic cancer lesion that can be biopsied with acceptable risk as determined by the Investigator, and an archival tumor tissue sample, if available. If a fresh tumor biopsy is not possible, then an archival tumor tissue sample must be provided. 5. Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 (Dose Escalation) or 0 to 1 (Dose Expansion) at Screening 6. Adequate organ function and bone marrow function. 7. If a female of childbearing potential must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements. 8. Male participants must agree to follow contraception requirements. 9. Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.
Exclusion Criteria:
1. Must not have received the following within the specified time periods prior to the first dose of study drug: 1. Prior therapies (anticancer or therapies given for other reasons) that are known strong or moderate inhibitors or inducers of CYP3A4 or P-gp including certain herbal medications (eg, St. John's Wort): 14 days or 5× the half-life of the medication (whichever is longer) 2. All other prior anticancer therapies or any therapy that is investigational for the participant's condition with a known safety and PK profile: 14 days or 5× the half-life of the medication (whichever is shorter) 3. Investigational therapies with unknown safety and PK profile: 28 days. If there is enough data on the investigational therapy to assess the risk for drug.-drug interactions and late toxicities of prior therapy as low, the Sponsor's Medical Monitor may approve a shorter washout of 14 days 4. Grapefruit or grapefruit juice: 14 days 2. Have not recovered from all toxicities from prior therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). 3. Presence or history of central nervous system (CNS) metastases or leptomeningeal disease, with some exceptions 4. New York Heart Association Class III or IV heart disease, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, congestive heart failure, or myocardial infarction within 6 months prior to the first dose of study drug. 5. Prolongation of the QT interval corrected by Fridericia's formula (QTcF) based on repeated demonstration of QTcF >450 ms in males or >470 ms in females at screening, or history of long QT syndrome. 6. Left ventricular ejection fraction (LVEF) <50% at Screening 7. Systemic arterial thrombotic or embolic events 8. Systemic venous thrombotic events 9. Malabsorption syndrome 10. Bone disease that requires ongoing treatment or has required treatment. 11. Major surgery within 4 weeks of the first dose of study drug. All surgical wounds must be healed and free of infection or dehiscence before the first dose of the study drug. 12. Any other clinically significant comorbidities. 13. For participants receiving DCC-3116 and trametinib combination or DCC-3116 and binimetinib combination: previous treatment with trametinib or binimetinib that resulted in treatment discontinuation due to intolerability as a result of an adverse event (AE) that was considered related to trametinib or binimetinib. 14. For participants receiving DCC-3116 and sotorasib combination in Dose Escalation Part 1: previous treatment with sotorasib that resulted in treatment discontinuation due to intolerability as a result of an adverse event (AE) that was considered related to sotorasib. 15. For participants receiving DCC-3116 and sotorasib combination: Use of proton pump inhibitors (PPIs) and H2 receptor antagonists that cannot be discontinued 3 days prior to the start of study drug administration. 16. Known allergy or hypersensitivity to any component of the investigational drug products. 17. Known human immunodeficiency virus unless the following requirements are met: 1. CD4 count >350/µL 2. No AIDS-defining opportunistic infection in the last 12 months 3. Stable anti-retroviral regimen with medications that are not prohibited by the protocol for at least 4 weeks with HIV viral load less than 400 copies/mL prior to enrollment. 18. Known active hepatitis B, active hepatitis C infection or if the participant is taking medications that are prohibited per protocol. 19. If female, the participant is pregnant or lactating. 20. Ongoing participation in an interventional study. 21. For participants receiving DCC-3116 and binimetinib combination: Known Gilbert's syndrome
Pancreatic Ductal Adenocarcinoma, Non-Small Cell Lung Cancer, Colorectal Cancer, Melanoma, Advanced Solid Tumor, Metastatic Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
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Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients With pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score Less Than or Equal to 25 (OFSET)

This Phase III Trial will determine whether adjuvant chemotherapy (ACT) added to ovarian function suppression (OFS) plus endocrine therapy (ET) is superior to OFS plus ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early- stage breast cancer (EBC) patients with estrogen receptor (ER)-positive, HER2-negative tumors and 21-gene recurrence score (RS) between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).
Malinda West, MD
Female
18 Years to 60 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05879926
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Inclusion Criteria:

• A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
• The patient or a legally authorized representative must provide study-specific informed consent prior to pre-entry and, for patients treated in the U.S., authorization permitting release of personal health information.
• Female patients must be greater than or equal to 18 years of age.
• Patients must be premenopausal (evidence of functioning ovaries) at the time of pre-entry. For study purposes, premenopausal is defined as:
• Age 50 years or under with spontaneous menses within 12 months; or
• Age greater than 50-60 years with spontaneous menses within 12 months plus follicle-stimulating hormone (FSH) and estradiol levels in the premenopausal range; or
• Patients with amenorrhea due to IUD or prior uterine ablation must have FSH and estradiol levels in the premenopausal range; or
• Patients with prior hysterectomy must have FSH and estradiol levels in the premenopausal range.
• The patient must have an ECOG performance status of less than or equal to 2 (or Karnofsky greater than or equal to 60%).
• Patients may have ipsilateral or contralateral synchronous breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
• Patients may have multicentric or multifocal breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
• Patient may have undergone a total mastectomy, skin-sparing mastectomy, nipple-sparing mastectomy, or a lumpectomy.
• For patients who undergo a lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS (ductal carcinoma in situ) with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. Positive posterior margin is allowed if surgeon deems no further resection possible. (Patients with margins positive for LCIS (lobular carcinoma in situ) are eligible without additional resection.)
• For patients who undergo mastectomy, the margins must be free of residual gross tumor. (Patients with microscopic positive margins are eligible if post-mastectomy RT (radiation therapy) of the chest wall will be administered.)
• Patient must have undergone axillary staging with sentinel node biopsy (SNB), targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
• The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
• By pathologic evaluation, primary tumor must be pT1-3. (If N0, must be T1c or higher.)
• By pathologic evaluation, ipsilateral nodes must be pN0 or pN1 (pN1mi, pN1a, pN1b, pN1c).
• Patients with positive isolated tumor cells (ITCs) in axillary nodes will be considered N0 for eligibility purposes.
• Patients with micrometastatic nodal involvement (0.2-2 mm) will be considered N1.
• Oncotype DX RS (recurrence score) requirements*:
• If node-negative:
• Oncotype DX RS must be RS 21-25, or
• Oncotype DX RS must be 16-20 and disease must be high clinical risk, defined as: low histologic grade with primary tumor size greater than 3 cm, intermediate histologic grade with primary tumor size greater than 2 cm, or high histologic grade with primary tumor size greater than 1 cm.
• If 1-3 nodes involved:
• Oncotype DX RS must be less than 26. * Patients with a "Low Risk" or "MP1" MammaPrint (a genomic test that analyzes the activity of certain genes in early-stage breast cancer) result must have eligibility assessed with an Oncotype DX RS at pre-entry (see Section 3.1). Blocks or unstained slides must be sent to the Genomic Health centralized laboratory for testing at no cost to these patients. If MammaPrint High Risk or MP2, these patients are not eligible.
• The tumor must be ER and/or PgR-positive (progesterone receptor) by current ASCO/CAP guidelines based on local testing results. Patients with greater than or equal to 1% ER and/or PgR staining by IHC will be classified as positive.
• The tumor must be HER2-negative by current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines based on local testing results.
• The interval between the last surgery for breast cancer (including re-excision of margins) and pre-entry must be no more than 16 weeks.
• Short course of endocrine therapy of less than 6 weeks duration before pre-entry is acceptable either as neoadjuvant or adjuvant therapy. An Oncotype DX RS must be performed on core biopsy specimen obtained prior to initiation of neoadjuvant endocrine therapy if received.
• Patients with a prior or concurrent non-breast malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. This would include prior cancers treated with curative intent.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Radiation therapy should be used according to standard guidelines; the intended radiation therapy should be declared prior to pre-entry.
Exclusion Criteria:

• • Definitive clinical or radiologic evidence of metastatic disease.
• pT4 (pathological state) tumors, including inflammatory breast cancer.
• History of ipsilateral or contralateral invasive breast cancer. (Patients with synchronous and/or previous DCIS or LCIS are eligible.)
• If prior ipsilateral DCIS was treated with lumpectomy and XRT (ionizing radiation therapy), a mastectomy must have been performed for the current cancer.
• Life expectancy of less than 10 years due to co-morbid conditions in the opinion of the investigator. Known results from most recent lab studies obtained as part of routine care prior to study entry showing ANY of the following values:
• ANC (absolute neutrophil count) less than 1200/mm3;
• Platelet count less than 100,000/mm3;
• Hemoglobin less than 10 g/dL;
• Total bilirubin greater than ULN (upper limit of normal) for the lab or greater than 1.5 x ULN for patients who have a bilirubin elevation due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin;
• AST(aspartate aminotransferase)(SGOT)/ALT (alanine transminase)(SGPT): greater than 3 × institutional ULN;
• Renal function of GFR (glomular filtration rate) less than 30 mL/min/1.73m2.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Any treatment with radiation therapy, chemotherapy, or biotherapy administered for the currently diagnosed breast cancer prior to pre-entry. (Patients with prior ET of more than 6 weeks duration for treatment of this cancer are not eligible.) Prior tamoxifen given for breast cancer prevention is allowed. Prior AI or GnRH for fertility preservation is allowed.
• Hormonally based contraceptive measures must be discontinued prior to pre-entry (including progestin/progesterone IUDs).
• Patients with evidence of chronic hepatitis B virus (HBV) infection are ineligible unless the HBV viral load is undetectable on suppressive therapy. Patients with a history of hepatitis C virus (HCV) infection are ineligible unless they have been treated and cured or have an undetectable HCV viral load if still on active therapy.
• Pregnancy or lactation at the time of pre-entry. (Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to pre-entry.)
• Other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
Breast, Breast Cancer
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Testing the Addition of High Dose, Targeted Radiation to the Usual Treatment for Locally-Advanced Inoperable Non-small Cell Lung Cancer

This phase III trial compares the effect of adding stereotactic body radiation therapy (SBRT) to standard treatment (image guided radiation therapy [IGRT] and chemotherapy followed by immunotherapy with durvalumab) versus standard treatment alone in treating patients with non-small cell lung cancer that cannot be treated by surgery (inoperable). SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. IGRT is a type of radiation that uses a computer to create picture of the tumor, to help guide the radiation beam during therapy, making it more accurate and causing less damage to healthy tissue. Standard chemotherapy used in this trial consists of combinations of the following drugs: cisplatin, carboplatin, paclitaxel, pemetrexed, and etoposide. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It works by stopping the growth and spread of tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by blocking the action of a certain substance in the body that may help tumor cells multiply. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Immunotherapy with durvalumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Adding SBRT to the standard treatment of IGRT with chemotherapy and immunotherapy may be more effective at treating patients with inoperable non-small cell lung cancer than giving the standard treatment alone.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05624996
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Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of stage II or III (American Joint Committee on Cancer [AJCC] eighth edition) non-small cell lung cancer (NSCLC) with known PD-L1 status prior to registration
• Patients must have an identified primary tumor and at least one nodal metastasis (peribronchial/hilar/intrapulmonary, mediastinal/subcarinal, supraclavicular/scalene)
• Up to 4 cycles of systemic therapy received prior to registration for the current study cancer is allowable; any prior chemotherapy for a different cancer is also permissible
• The patient must be deemed clinically appropriate for curative intent definitive combined modality therapy, based on the following staging assessments:
• History/physical examination prior to registration;
• Magnetic resonance imaging (MRI) scan of the brain (preferred) or CT scan of the brain (if available, contrast is preferred for all neuroimaging) prior to registration;
• CT chest with IV contrast (if contrast is available and unless contraindicated, such as for abnormal kidney function) prior to registration. PET/CT may be used if the CT portion is of identical diagnostic quality as achieved in a stand-alone CT
• No evidence of distant metastases based on FDG PET/CT scan obtain within 60 days of registration
• Primary tumor =< 7 cm
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Hematologic function (e.g. platelets, leukocytes, hemoglobin) amenable, at the discretion of the treating physician, to allow for treatment with chemotherapy and concurrent radiation therapy
• Creatinine clearance >= 25 mL/min by the Cockcroft-Gault (C-G) equation
• Subjects with non-malignant pleural effusion are eligible provided the effusion is not known or demonstrated to be an exudative effusion
• If a pleural effusion is present, the following criteria must be met to exclude malignant involvement:
• When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative;
• Effusions that are minimal (i.e., not visible on chest x-ray) that are too small to safely tap are eligible
• Medical history consistent with the patient being amenable, at the discretion of the treating physician, to allow for treating with consolidation immunotherapy. Patients with known EGFR/ALK mutation at the time of registration are eligible, and these patients can be treated with consolidation durvalumab or chemotherapy at the discretion of the treating physician
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Negative pregnancy test =< 14 days prior to registration for participants of childbearing potential
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:

• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields that is determined by the treating physician to impede the treatment of the study malignancy
• Patients without identifiable primary tumor and at least 1 pathologically enlarged lymph node are not eligible (T3-4N0 or T0N1-3 patients are not eligible). At least 1 radiographically-involved lymph node is required, but pathologic confirmation of involvement is not mandated
• Centrally located primary tumor < 2 cm from involved nodal disease which would result in significant overlap of the primary SBRT and nodal radiation fields. Centrally located is defined as within or touching the zone of the proximal bronchial tree, which is a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus right and left lower lobe bronchi)
• Participants who are pregnant or unwilling to discontinue nursing
• Participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) unwilling to use highly effective contraceptives during therapy and for the Food and Drug Administration (FDA)-labeled contraception timeframe required after the final dose of the selected chemotherapy regimen, because the treatment in this study may be significantly teratogenic
Lung, Locally Advanced Lung Non-Small Cell Carcinoma, Stage IIB Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8
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A Study of Alpelisib and Fulvestrant to Treat Endometrial Cancer

This is a 2 stage multi-center study designed to evaluate the efficacy of the combination of alpelisib and fulvestrant in patients with PIK3CA-mutated ER-positive endometrioid endometrial cancers by estimating the objective response rate (ORR). Treatment will continue until either unacceptable toxicity, progression of disease, or investigator/patient request for withdrawal.
Janelle Sobecki, MD
Female
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05154487
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Inclusion Criteria:
1. Patient must have advanced (FIGO 2014 Stage III or IV), persistent, or recurrent endometrial carcinoma, which is not likely to be curable by surgery or radiotherapy. Histologic confirmation of recurrent disease is required. For cases of persistent disease, histologic confirmation of the primary disease with radiologic evidence of progression is required. 2. Patients must have endometrioid histology (all grades allowed) based on hysterectomy or biopsy specimen and have positive expression of ER and oncogenic PIK3CA mutation per criteria below. a. PIK3CA mutations considered oncogenic include R88Q, N345K, C420R, E542K, E545X, Q546X, M1043I, H1047X, or G1049R. The list of oncogenic mutations acceptable for enrollment may be expanded as further information becomes available. i. Oncogenic PIK3CA mutations identified on tests performed by the labs listed on https://ecog-acrin.org/nci-match-eay131-designated-labs will be considered confirmed for the purposes of this study ii. Oncogenic PIK3CA mutations identified by other tests will need to be confirmed by the study prior to enrollment b. Estrogen receptor (ER) status will be considered positive if ≥1% of tumor cells demonstrate positive nuclear staining by immunohistochemistry. Pathology report documenting ER status must be provided at enrollment. Sites are required to report results of previous MMR and/or MSI status testing in Medidata Rave if available. 3. All patients must have measurable disease. Measurable disease is defined by RECIST version 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be greater than or equal to 10mm when measured by CT, MRI or caliper measurement by clinical exam; or greater than or equal to 20mm when measured by chest x-ray. Lymph nodes must be greater than or equal to 15mm in short axis when measured by CT or MRI. Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy. 4. Prior chemotherapy in the adjuvant setting for Stage I, II, or III is permitted. Prior chemoradiotherapy for a pelvic recurrence is permitted. Note: No prior chemotherapy in the setting of Stage IV disease is permitted unless the patient was without evidence of disease at the completion of chemotherapy and had a least six months of progression-free survival since the completion of chemotherapy. Regardless of circumstances, no more than one prior chemotherapy regimen (including chemo-radiotherapy) is permitted. Patients who received prior chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A washout period of at least 21 days is required between last chemotherapy dose and initiation of therapy. Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and initiation of therapy. 5. Patient must be able to swallow oral medications. 6. Patient must have an ECOG performance status of 0 to 1. 7. Patients must have adequate glucose control as defined by the following (both criteria must be met):
• Fasting blood glucose (FBG) ≤140/dL (7.7mmol/L) AND
• Hemoglobin A1c (HbA1c) ≤6.4% 8. Patients must have adequate organ and marrow function as defined below NOTE: Institutional/laboratory upper limit of normal = ULN Institutional/laboratory lower limit of normal = LLN Bone marrow function:
• Absolute neutrophil count (ANC) greater than or equal to 1500/mcl
• Platelets greater than or equal to 100,000 cells/mcl
• Hemoglobin greater than or equal to 8 g/dL (Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after erythrocyte transfusion). Renal function: • Creatinine Clearance ≥ 35 mL/min using Cockcroft-Gault formula Pancreatic function:
• Fasting Serum amylase ≤ 2 × ULN
• Fasting Serum lipase ≤ ULN Hepatic function:
• Bilirubin less than or equal to 1.5 x ULN (Patients with Gilbert's syndrome with a total bilirubin ≤2 times ULN and direct bilirubin within normal limits are permitted).
• ALT (alanine aminotransferase) and AST (aspartate aminotransferase) less than or equal to 3 x ULN
• Alkaline phosphatase less than or equal to 2.5 x ULN
• Albumin greater than or equal to 2.8 g/dL 9. Patients must have signed an approved informed consent and authorization permitting release of personal health information. 10. Patients must be at least 18 years of age. 11. Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing a highly effective form of contraception during the study treatment and for 8 weeks after stopping the treatment. Highly effective contraception methods include combination of any of the following (oral, injected, or implanted hormonal contraceptives are prohibited:
• Placement of an intrauterine device (IUD) or intrauterine system (IUS);
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository;
• Total abstinence or;
• Male/female sterilization. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.
Exclusion Criteria:
1. Patients who have previously received any PIK3CA, PI3K, mTOR, or AKT inhibitor. 2. Patients with clear cell, serous, carcinosarcoma, mixed histology endometrial cancers, or uterine sarcomas. 3. Known intolerance or hypersensitivity to alpelisib or fulvestrant, or any of their excipients. 4. Patients who have previously received hormonal therapy for endometrial cancer. 5. Participant has had major surgery within 14 days prior to study treatment start and/or has not recovered from major side effects. 6. Participant with an established diagnosis of diabetes mellitus type I or uncontrolled type II (based on fasting blood glucose [FBG] and HemoglobinA1c [HbA1c], see INCLUSION CRITERION 7) 7. Patients with concomitant invasive malignancy or a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the past five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol. 8. Patients with active bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment, fungal infection, or detectable viral infection (such as known human immunodeficiency virus (HIV) positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]). Screening is not required for enrollment. 9. Patients with a serious pre-existing medical condition(s) that would preclude participation in this study (for example: interstitial lung disease or pneumonitis, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment (i.e. estimated creatinine clearance <30ml/min), history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or pre-existing chronic condition resulting in baseline grade 2 or higher diarrhea). 10. Patients with a known history of cardiac disease. This includes:
• Uncontrolled hypertension, defined as systolic greater than 150mm Hg or diastolic greater than 90mm Hg despite antihypertensive medications
• Myocardial infarction, unstable angina, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to registration.
• New York Heart Association (NYHA) Class II or greater congestive heart failure.
• History of clinically significant cardiac arrhythmias (i.e. ventricular tachycardia or ventricular fibrillation, complete left bundle branch block, high grade AV block (e.g. bifascicular block, Mobitz type II and third degree AV block without pacemaker in place) or serious cardiac arrhythmia requiring medication. This does not include asymptomatic atrial fibrillation with controlled ventricular rate.
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or Fridericia QT correction formula (QTcF) > 470 msec at screening.
• Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6 months prior to the first date of study therapy.
• Syncope of cardiovascular etiology,
• Sudden cardiac arrest. 11. Participant is currently receiving any of the following medications and cannot be discontinued 7 days prior to the start of the treatment:
• Strong CYP3A4 inducers
• Inhibitors of BCRP. 12. Patients who are pregnant or breast-feeding. 13. Patients with known central nervous system metastases which was not previously treated and not fulfilling the following 3 criteria to be eligible for the study:
• Completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 28 days prior to the start of study entry and
• CNS tumor is clinically stable at the time of screening and
• Participant is not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases. 14. Patients with an impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study drugs (i.e. ulcerative disease; uncontrolled nausea, vomiting and/or diarrhea; malabsorption syndrome; clinical signs and symptoms of gastrointestinal obstruction; and/or patients who require parenteral hydration and/or nutrition). 15. Patients who plan to receive live attenuated vaccines within 1 week of start of alpelisib and during the study. Patients should also avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG< yellow fever, varicella, and TY21a typhoid vaccines. 16. Patients with active bleeding or pathologic conditions that carry high risk of bleeding such as known bleeding disorder or coagulopathy. 17. Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 30 days prior to dosing, or within 5 half-lives of the investigational product, whichever is longer. 18. Patient is not able to understand and to comply with study instructions and requirements, including oral administration of study treatment.
Endometroid Endometrial Cancer, Corpus Uteri, Uterus
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A Study to Characterize the Safety, Tolerability, and Preliminary Efficacy of CFT1946 as Monotherapy and in Combination With Trametinib in Subjects With BRAF V600 Mutant Solid Tumors

The purpose of this study is to evaluate the safety and tolerability of CFT1946 as well as to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of CFT1946 as monotherapy (Arm A) and in combination with trametinib (CFT1946 + trametinib; Arm B).
Vincent Ma, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05668585
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Inclusion Criteria:
1. Subject (or legally authorized representative, where applicable) is willing and able to provide signed informed consent and can follow protocol requirements 2. Subject is ≥18 years of age at time of informed consent 3. Eastern Cooperative Oncology Group performance status of 0 or 1 4. Subject has documented evidence of a BRAF V600 mutation obtained from tumor tissue or liquid biopsy: (other protocol conditions may apply) 5. Subject must have received ≥1 prior line of SoC therapy for their unresectable locally advanced or metastatic disease with disease progression on or after last prior treatment. Prior regimens for these subjects vary by indication and investigational arm, but must have included the following: 1. Melanoma or NSCLC (Phase 1 and Phase 2 Arms A1 and B1): Prior receipt of a BRAF inhibitor and an immune checkpoint inhibitor (any sequence or combination). Prior (neo)adjuvant immunotherapy may be acceptable. 2. CRC: Receipt of a systemic chemotherapy-based regimen per SoC for unresectable locally advanced or metastatic disease, and previous treatment with BRAF inhibitor in combination with an EGFR monoclonal antibody. Subjects with documented MSI-H or dMMR CRC must have received prior immunotherapy. Subjects with MSS disease must have received at least 2 prior treatments. Subjects who received neo(adjuvant) chemotherapy regimens may be eligible. 3. ATC: Subjects must have received SoC therapy options including BRAF inhibitor if available and of benefit to the subject 4. Other BRAF V600 mutant solid tumors (non-CNS): Subjects must have received SoC therapy options per their Investigator's best judgment, including BRAF inhibitor if available and of benefit to the subject 6. Subject has measurable disease per RECIST v1.1 7. Adequate bone marrow, liver, renal, and cardiac function 8. A female subject may be eligible if not pregnant, planning a pregnancy, not breast feeding, a women of non-child bearing potential or a WOCBP willing to comply with protocol conditions relating to the use contraception, ova or blood donation and pregnancy testing prior to the first dose 9. A male subject must agree to comply with protocol conditions relating to the use of contraception, sperm and blood donation 10. Subject can safely swallow a tablet or pill Other protocol defined exclusion criteria may apply
Exclusion Criteria:
1. Subject has had major surgery within 21 days prior to the planned first dose. Minor surgery is permitted within 21 days prior to enrollment 2. Subject with CNS involvement (primary tumor or metastatic disease), except if clinically stable, have no evidence of new or enlarging brain metastases and are on stable or tapering doses of steroids for at least 7 days prior to first dose. Subjects with untreated brain metastases may be eligible to enter without prior radiation therapy. 3. Subject with known malignancy other than trial indication that is progressing or has required treatment within the past 3 years, except for conditions that have undergone potentially curative therapy 4. Subject with history of thromboembolic or cerebrovascular events ≤6 months as defined in the protocol 5. Subject with impaired cardiac function or clinically significant cardiac disease, as defined in the protocol 6. Subject with history of uncontrolled diabetes mellitus (only for subjects who will receive CFT1946 + trametinib) 7. Subject with history or current evidence of retinal vein occlusion (RVO), chorioretinopathy, or current risk factors for RVO (only for subjects who will receive CFT1946 + trametinib) 8. Subject has received live, attenuated vaccine within 28 days prior to first dose administration 9. Subject has history of pneumonitis or interstitial lung disease 10. Subject has history of uveitis 11. Subject has known human immunodeficiency virus (HIV) infection (with exceptions) 12. Subject has history of or known HBV or active HCV infection 13. Subject has concurrent administration of strong CYP3A4/5 inhibitors and inducers, including any herbal medications/supplements 14. Subject has presence of Grade ≥2 toxicity due to prior cancer therapy, excepting alopecia and hypothyroidism requiring thyroid replacement therapy 15. Subject has initiation or receipt of the following ≤7 days prior to first dose administration: Hematopoietic colony-stimulating growth factors, transfusion of packed red blood cells (pRBC), and transfusion of platelets 16. Subject is pregnant, breastfeeding, or expecting to conceive or father children any time during the study Other protocol defined exclusion criteria may apply
Solid Tumors, Melanoma, NSCLC, CRC, ATC, Colon, Rectum, Lung, Melanoma, Skin, Thyroid, Colon and Rectum, Melanoma/Skin cancer
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A Study to Evaluate the Safety and Efficacy of K-321 Eye Drops After Descemetorhexis in Participants With Fuchs Endothelial Corneal Dystrophy (FECD)

A study to assess the safety and efficacy of K-321 in participants with FECD after descemetorhexis.
Evan Warner
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05795699
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Inclusion Criteria:

• Is at least 18 years old at the screening visit (Visit 1)
• Has a diagnosis of FECD at Visit 1
• Meets all other inclusion criteria outlined in clinical study protocol
Exclusion Criteria:

• Is a female patient of childbearing potential and any of the following is true: 1. is pregnant or lactating/breastfeeding, or 2. is not surgically sterile, not post-menopausal (no menses for the previous 12 months), or not practicing an effective method of birth control as determined by the Investigator (eg, oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy)
• Has a study eye with a history of cataract surgery within 90 days of Visit 1
• Meet any other exclusion criteria outlined in clinical study protocol
Fuchs Endothelial Corneal Dystrophy, Other, Eye & Vision
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Comparison of Microglial Activation in Severe Asthma and Healthy Controls (MAIA-SC)

The goal of this clinical trial is to learn about how asthma influences brain function. The main questions it aims to answer are: - How airway inflammation in asthma affects the brain; and, - Whether airway inflammation in asthma is related to symptoms of depression and anxiety Over the course of 3 visits, participants will: - Complete questionnaires - Complete computer tasks - Undergo allergy skin test and breathing tests - Give two blood samples - Give a sputum sample - Complete brain imaging scans Researchers will compare results between participants with asthma, and participants who do not have asthma.
Melissa Rosenkranz, PhD
All
18 Years to 75 Years old
N/A
This study is also accepting healthy volunteers
NCT06299592
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Inclusion Criteria:

• Ability to understand and the willingness to sign a written informed consent document
• Individuals with no health concerns that might affect the outcome of the study
• Age 18-75 years of age
• Ability to tolerate a simulated MRI brain scanning session
• In the opinion of the investigator, capable and willing to grant written informed consent and cooperate with study procedures and requirements
• High-affinity TSPO-binding genotype. Mixed (high/low) binding-affinity genotype may be included at PIs discretion
• For participants with severe asthma:
• Physician diagnosis of asthma for at least six months prior to screening (can be determined at the discretion of an asthma/allergy physician member of the study team)
• Severe asthmatics must meet the ATS definition of severe asthma and/or be currently receiving a GINA 5 therapy (or greater), which may include ongoing use of currently approved biologic immunomodulators
Exclusion Criteria:

• Current smoker (defined as more than 0.5 pack per week for the past 6 months and any smoking within two weeks of study procedures) or has a smoking history exceeding 5 pack years within the last 10 years
• Currently receiving immunotherapy
• Use of psychotropic medication that might affect function of neurocircuitry implicated in our hypotheses (at the discretion of the PI/Co-I)
• Inability to hold medications detailed in the medication hold schedule
• Needle phobia or claustrophobia
• Major health problems such as autoimmune disease, history of carotid stenosis, heart disease, uncontrolled hypertension, or lung diseases other than asthma, history of significant arrhythmias, and any of the following in the last 6 months: stroke/TIA, myocardial infarction, stent placement, or acute coronary syndrome. The listed health problems are definitively exclusionary, but decisions regarding major health problems not listed will be based upon the judgment of the investigator
• Use of biologic medication that might affect signaling pathways under investigation (at the discretion of the PI/Co-I)
• Pre-existing chronic infectious disease
• Scheduled use of non-selective beta-blockers prior to each study visit.
• Use of an investigational drug within 30 days of entering the study. This criterion will be reviewed on a case by case basis by the PI/Co-I to determine appropriate washout period. Appropriate wash out period may be greater than 30 days depending on the half-life of the investigational drug. Participants may be eligible for study participation after completing the washout period designated by the PI or Co-I (physician only).
• Any MRI incompatibility as determined by most current MRI screening form
• History of a diagnosed bipolar disorder, schizophrenia, or schizoaffective disorder
• History of serious head trauma or seizure disorder (can be included at the discretion of the PI or Co-I)
• Unable, in the judgement of the investigator, to comply with directions and/or tolerate the procedures required for participation in this study
• Pregnant or breast-feeding or has a planned pregnancy during the course of the study
• Any other medical condition or disease that would impact participant safety or data integrity in the opinion of the PI/CO-I
Asthma, Other, Infections, Immune System & Allergies, Healthy Volunteers
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A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression (RECOVER)

Objectives of this study are to determine whether active VNS Therapy treatment is superior to a no stimulation control in producing a reduction in baseline depressive symptom severity, based on multiple depression scale assessment tools at 12 months from randomization.
Steven Garlow, MD, PhD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03887715
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Inclusion Criteria:
The patient must be in a major depressive disorder (MDD) episode for ≥ two years or have had at least four episodes of MDD, including the current episode. The patient's depressive illness meets a minimum criterion of four prior failed treatments of adequate dose and duration as measured by a tool designed for this purpose. The patient is experiencing a major depressive episode (MDE) as measured by a guideline recommended depression scale assessment tool on two visits, within a 45-day span prior to implantation of the VNS device. Patients must maintain a stable medication regimen for at least four weeks before device implantation.
Exclusion Criteria:
Current or lifetime history of psychotic features in any MDE; Current or lifetime history of schizophrenia or schizoaffective disorder; Current or lifetime history of any other psychotic disorder; Current or lifetime history of rapid cycling bipolar disorder; Current secondary diagnosis of delirium, dementia, amnesia, or other cognitive disorder; Current suicidal intent; or Treatment with another investigational device or investigational drugs.
Treatment Resistant Depression, Bipolar disorder, Major depressive disorder, recurrent, Other
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