Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
437 Study Matches
A Study to Learn More About How Risankizumab Works in Young Participants With Ulcerative Colitis (MIGHTY)
Ulcerative colitis (UC) is a type of inflammatory bowel disease that causes inflammation and bleeding from the lining of the rectum and colon (large intestine). This study will assess how Risankizumab moves through the body as well as how safe and effective it is in treating pediatric participants with moderate to severely active UC. Adverse events and change in disease activity will be assessed.
Risankizumab is an approved medication for moderate to severe UC in multiple countries and is being developed for the treatment of UC in pediatrics. This study is comprised of 3 cohorts that may participate in 3 substudies (SS). Cohort 1 will enroll participants with ages from 6 to less than 18 years. Cohort 2 will enroll participants with ages from 2 to less than 6 years. Cohort 3 will enroll participants with ages from 2 to less than 18 years. SS1 is an open-label induction period where participants will receive a weight-based induction regimen of risankizumab. SS2 is a double-blind maintenance period where participants will be randomized to receive 1 of 2 doses of weight-based maintenance regimen of risankizumab. SS3 is an open-label extension period where participants will receive risankizumab based off of their response in SS2. Around 120 pediatric participants with UC will be enrolled at around 80 sites worldwide.
Participants in SS1 will receive risankizumab intravenously during the 12-week induction period. Participants in SS2 will receive risankizumab subcutaneously during the 52-week randomized maintenance period. Participants in SS3 will receive risankizumab subcutaneously during the 208-week open label period. Participants will be followed-up for approximately 140 days.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
studyfinder@utsouthwestern.edu
ALL
2 Years to 17 Years old
PHASE3
This study is NOT accepting healthy volunteers
NCT07071519
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Inclusion Criteria:
* Active ulcerative colitis (UC) with an modified Mayo Score (mMS) of 5 to 9 points and endoscopic subscore of 2 to 3 (confirmed by central reader).
* Demonstrated intolerance or inadequate response (IR) to one or more of the following categories of drugs:
aminosalicylates (except in countries where failure of this drug class is not sufficient for eligibility), oral locally acting corticosteroids, systemic steroids (prednisone or equivalent), immunomodulators (IMMs), and/or biologic therapies, as outlined in the protocol.
\- Subjects must have a documented history of UC for at least 3 months prior to Baseline, confirmed by colonoscopy during the screening period, with exclusion of current infection, colonic dysplasia and/or malignancy. Documentation of pathology results consistent with the diagnosis of UC must be available.
Exclusion Criteria:
* Participants who have had a major surgery performed within 12 weeks prior to Baseline or planned during the conduct of the study (e.g., inguinal hernia repair, cholecystectomy, intestinal resection).
* Participants who have concurrent clinically significant medical conditions other than the indication being studied or any other reason that the investigator determines would interfere with the subject's participation in this study, would make the subject an unsuitable candidate to receive study treatment, or would put the subject at risk by participating in the study.
A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of Niemann-Pick Type C Disease, GM1 Gangliosidosis or GM2 Gangliosidosis
An 18-month double-blind, randomized, placebo-controlled, multicenter, Phase 3 study to evaluate the safety and efficacy of oral nizubaglustat (AZ-3102) in late-infantile and juvenile forms of Niemann-Pick type C disease and in late-infantile and juvenile-onset forms of GM1 gangliosidosis or GM2 gangliosidosis
* Male and female participants, aged 4 years and older with a diagnosis of the late-infantile or juvenile form of NPC disease. Detailed inclusion criteria are presented in the NPC disease-specific subprotocol AZA-001-301-NPC (NCT07082725).
* Male and female participants, aged 4 years and older with a diagnosis of GM1 or GM2 (Tay-Sachs, Sandhoff, or GM2AB variant disease) gangliosidosis of late-infantile/ juvenile onset. Detailed inclusion criteria are presented in the GM1/GM2 gangliosidosis-specific subprotocol AZA-001-301-GMx (NCT07082543).
Exclusion Criteria:
* Detailed exclusion criteria are presented in the NPC disease-specific subprotocol AZA-001-301-NPC
* Detailed exclusion criteria are presented in the GM1/GM2 gangliosidosis-specific subprotocol AZA-001-301-GMx
DRUG: AZ-3102, DRUG: Placebo
Niemann-Pick Type C Disease, GM1 Gangliosidosis, GM2 Gangliosidosis
A Study to Evaluate the Safety and Efficacy of Oral Nizubaglustat (AZ-3102) in Late-infantile and Juvenile Forms of Niemann-Pick Type C Disease (NPC)
An 18-month double-blind, randomized, placebo-controlled, multicenter, Phase 3 study to evaluate the safety and efficacy of oral nizubaglustat (AZ-3102) in late-infantile and juvenile forms of Niemann-Pick type C disease
* Signed informed consent
* Confirmed diagnosis of NPC disease
* Patient is unable or unwilling to take miglustat, or is, in the opinion of the investigator, unsatisfactorily treated with miglustat
* Male and female participants aged 4 years and older at the time of informed consent
* Onset of neurological symptoms from 2 to 15 years
* Disability level at Baseline: Ataxic disturbances with a total SARA score of ≥3 and ≤30 at Baseline
* Female of childbearing potential who are sexually active willing to follow the contraceptive guidance
* Male participants with a female partner of childbearing potential willing to follow the contraceptive guidance
Exclusion Criteria:
* A history of medical conditions other than NPC disease that, in the opinion of the Principal Investigator, would confound scientific rigor or the interpretation of results
* Body weight of \<10 kg
* The presence of another neurologic disease
* The presence of moderate or severe hepatic impairment
* The presence of moderate or severe renal impairment
* Platelet count of \<100x10\^9/L
* The dose of any anti-epileptic treatment(s) was not stable (required a change in dose within the previous 3 months) and/or a new anti-epileptic treatment (drug or procedure) was prescribed in the month before Baseline
* Prior use of an investigational drug within the 3 months before Screening; or prior participation in a clinical study involving gene therapy or stem cell transplantation within 2 years prior to Screening
* A positive serum pregnancy test (for women of childbearing potential)
* Current treatment with miglustat, provided the patient has been using the recommended dose for most of the past 12 months AND is, in the opinion of the investigator, satisfactorily treated with miglustat. Any participants receiving miglustat are required to undergo a 1-month washout period before starting study medication
The current study aims to investigate whether combining the standard medications prescribed after acute coronary syndrome (ACS)-aspirin, P2Y12 inhibitors, and statins-into a single polypill can improve outcomes following an ACS event. Although these therapies are effective, gaps in adherence and uptake significantly contribute to risk or adverse events in the post-ACS period. This study is designed as a pragmatic, multi-center, randomized trial to assess the feasibility and effectiveness of a polypill-based strategy for treatment of ACS.
* Age ≥ 18
* Hospitalization for acute coronary syndrome with percutaneous coronary intervention
* Discharged on aspirin, prasugrel or clopidogrel, and a high-intensity statin
Exclusion Criteria:
* Current need for systemic anticoagulation
* Contraindication to receive any components of the polypill
* History of allergic reaction or intolerance to aspirin, prasugrel or clopidogrel, or rosuvastatin
* Comorbidities that might be expected to limit lifespan within the 12-month study period
* Increased risk of bleeding or planned urgent surgery that would necessitate use of DAPT for \< 12 months
* Inability to provide written informed consent
* Pregnancy
COMBINATION_PRODUCT: Polypill
Acute Coronary Syndrome, Cardiovascular
Acute Coronary Syndrome, Polypill, Adherence
UT Southwestern; Parkland Health & Hospital System
Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity (MARITIME-CV)
The primary objective of this trial is to demonstrate that maridebart cafraglutide is superior to placebo when given as an adjunct to standard of care with respect to reducing cardiovascular (CV) morbidity and mortality.
Inclusion Criteria
* Age ≥ 45 years at screening.
* BMI of ≥ 27.0 kg/m\^2 at screening.
* History of Atherosclerotic Cardiovascular Disease (ASCVD) with a documented history of at least one of the following:
* Prior MI (presumed atherothrombotic event due to plaque rupture/erosion).
* Prior ischemic stroke (presumed due to atherosclerosis; may include ischemic stroke with hemorrhagic transformation).
* Symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) \< 0.9 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease.
Exclusion Criteria
* History of any of the following within 60 days before screening or between screening and randomization: MI, hospitalization for unstable angina, arterial revascularization (eg, coronary, cerebrovascular or peripheral) major cardiovascular surgery, stroke, or transient ischemic attack (TIA).
* New York Heart Association (NYHA) class IV HF during screening or hospitalization for HF within 60 days before screening or between screening and randomization.
* Type 1 DM, or any other type of diabetes with the exception of T2DM or prior gestational diabetes. Participants with a history of gestational diabetes should be stratified according to their current diabetes classification.
* For participants with T2DM (including those without a prior history of T2DM but with a HbA1c ≥ 6.5% during screening):
* HbA1c \> 10.0% (86 mmol/mol) at screening.
* History of diabetic ketoacidosis or hyperosmolar state/coma within 12 months before randomization.
* One or more episodes of severe hypoglycemia within 6 months before randomization and/or history of hypoglycemia unawareness.
* History of proliferative diabetic retinopathy, diabetic maculopathy, severe non-proliferative diabetic retinopathy, or currently receiving or planning to receive treatment for diabetic retinopathy and/or diabetic macular edema.
* Use of any glucagon-like peptide-1 receptor agonist (GLP-1 RA), glucose-dependent insulinotropic polypeptide (GIP) agonists or antagonists, or amylin analogs within 90 days before randomization or planned use during the conduct of the trial.
* History of chronic pancreatitis or history of acute pancreatitis in the 180 days before screening or between screening and randomization.
* Family (first-degree relative\[s\]), or personal history of medullary thyroid carcinoma (MTC), or multiple endocrine neoplasia syndrome type 2 (MEN-2).
* Calcitonin ≥ 50 ng/L (pg/mL) at screening.
* Acute or chronic hepatitis; signs and symptoms of any liver disease other than metabolic dysfunction-associated steatotic liver disease, or alanine aminotransferase (ALT) \> 3.0 x the upper limit of normal (ULN) during screening, or total bilirubin (TBL) \> 1.8 x ULN during screening (for participants with a known diagnosis of Gilbert syndrome, direct bilirubin should be used instead of TBL).
* History of malignancy within the last 5 years before screening or between screening and randomization (except for the following treated with curative intent: non-melanoma skin cancer, breast ductal carcinoma in situ, cervical carcinoma in situ, or prostate cancer in situ).
* Participants of childbearing potential planning to become pregnant while on study or unwilling to use protocol-specified methods of contraception during treatment.
REGN7508 Versus Apixaban and Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty in Adults (ROXI-APEX)
This study is researching an experimental drug called REGN7508 (called "study drug"). The study is focused on adults undergoing elective, unilateral (one side) total knee replacement surgery.
The aim of the study is to see how effective the study drug is at preventing Venous Thromboembolism (VTE) and other related diseases after total knee replacement surgery.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drug
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects)
• Is undergoing a primary elective unilateral TKA
• Is in good health based on laboratory safety testing as described in the protocol
• Body weight ≤130 kg at screening visit as described in the protocol
Key
Exclusion Criteria:
• Any condition that, as assessed by the investigator, may confound the results of the study or pose an additional risk to the participant by study participation
• History of bleeding in the 6 months prior to randomization requiring hospitalization or transfusion as described in the protocol
• History of thromboembolic disease or thrombophilia
• History of major surgery, including brain, spinal, or ocular, or major trauma within approximately the past 6 months prior to randomization
• Has an estimated Glomerular Filtration Rate (GFR) of \<30 mL/min/1.73 m2 at the screening visit as described in the protocol
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Efficacy of Tezepelumab in Peanut Oral Immunotherapy (ZENITH)
The proposed study is a proof-of-concept Phase 2, double-blind, randomized placebo-controlled clinical trial evaluating the safety and efficacy of tezepelumab and peanut Oral Immunotherapy (OIT) for the treatment of peanut allergy. Study participation is divided into 3 periods: (i) a monotherapy period comprised of injections of either Tezepelumab or placebo from week 0 to week 8, (ii) followed by a combination therapy period comprised of 56 weeks during which peanut OIT is built up and maintained, and (iii) a treatment withdrawal period comprised of 12 weeks. This study will enroll 62 peanut-allergic individuals from 12 to 55 years of age who experience dose-limiting symptoms to \<=100 mg of peanut protein in a single dose (\<= 144 mg cumulative dose) as assessed by DBPCFC.
The primary objective is to determine whether 56 weeks of tezepelumab plus peanut OIT as compared to 56 weeks of placebo plus peanut OIT induces sustained unresponsiveness to peanut 12 weeks after stopping combination therapy.
studyfinder@utsouthwestern.edu
ALL
12 Years to 55 Years old
PHASE2
This study is NOT accepting healthy volunteers
NCT07015996
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Inclusion Criteria:
• Participant and/or parent/legal guardian must be able to understand and provide informed consent (parental permission and informed assent of minor, if applicable).
• Age 12 to 55 years inclusive with a personal history of an allergic reaction to peanut ingestion
• A positive reaction at or below ingestion of 100 mg of peanut protein in a single dose (≤ 144 mg cumulative dose) during the Screening DBPCFC
• A negative challenge to the placebo (oat) during the Screening DBPCFC
• Sensitization to peanut as evidenced by either one of the following:
• positive sIgE to Ara h2 ≥ 0.35 kU/L by ImmunoCAPTM testing, or
• wheal ≥ 3 mm on skin prick test to peanut extract compared to a negative control
• Female participants of childbearing potential must have a negative pregnancy test upon study entry
• Female participants with reproductive potential must agree to use an FDA approved method of contraception for the duration of the study
• Willing and able to comply with the study protocol requirements
• Participants with other food allergies must agree to continue avoidance of these food items from their diet to avoid confounding the safety and efficacy data of the study
Exclusion Criteria:
• Currently in build-up phase of aeroallergen immunotherapy
• Current food allergen immunotherapy or use of any food allergen immunotherapy within the past 12 months
• Pregnant, planning a pregnancy during the study, or breast-feeding
• History of intolerance, hypersensitivity, or allergic reactions to tezepelumab, or the inactive ingredients (excipients) of tezepelumab, other IgG biologics, or rescue medications and their excipients
• Allergy to oat (participant reported)
• History of severe systemic allergic reaction to peanut with symptoms including the need for mechanical ventilation and/or severe hypotension requiring intensive care unit admission
• Asthma requiring high dose inhaled corticosteroid therapy for control (2007 NHLBI Criteria Steps 5 or 6 in adults and adolescents)
• History of a life-threatening asthma attack within 12 months prior to screening (e.g., requiring an ICU admission or intubation with mechanical ventilation), need for oral corticosteroids for asthma management within the last 6 months, or current Asthma Control Test score less than 19 at screening
• History of ischemic cardiovascular disease or other cardiac disease, which, in the opinion of the site investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study
• History of eosinophilic gastrointestinal disease at screening
• History of disease affecting the immune system such as autoimmune disease (e.g., systemic lupus erythematosus), immune complex disease (e.g., serum sickness), or immunodeficiency, which, in the opinion of the site investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study
• History of malignancy of any type, excluding basal cell and squamous cell cancers of the skin that only required surgical excision or in situ carcinoma of the cervix study provided that curative therapy was completed at least 12 months prior to screening
• Current known helminth infection
• Positive QuantiFERON - TB Gold test or TB Gold Plus, or T-SPOT® TB test unless the potential participant has been treated with appropriate chemoprophylaxis. In the case of an indeterminate or borderline Interferon Gamma Release Assay (IGRA), an IGRA may be repeated.
• Any of the following:
• HIV
• Current or prior infection with hepatitis B virus (HBV)
• Current or prior infection with hepatitis C virus (HCV), except adequately treated HCV with sustained virologic response ≥ 12 weeks.
• Active liver disease, defined as either:
• AST, ALT, and/or Alk phos \>2x ULN, or
• other active liver disease which, in the opinion of the site investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study
• Any of the following:
• Current use of beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers
• Received any investigational product within the past 4 months or 5 half-lives (whichever is longer) prior to screening
• Received systemic corticosteroids within 14 days prior to screening
• Receipt of immunoglobulin or other blood product within 30 days prior to screening
• Receipt of live attenuated vaccine within 30 days prior to screening
• Use of an immunosuppressant or immunomodulating drug within 30 days prior to screening
• Use of biologics targeting the human immune system within the past 12 months prior to screening
• Use of any herbal medications, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the site investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study
* Age 18 years or older at the time of signing the ICF
* ECOG performance status of 0 to 1 for the dose escalation (Part 1a) and 0 to 2 for the dose expansion (Part 1b)
* Documented CALR exon-9 mutation
* Confirmed diagnosis of MPN according to the 2022 ICC criteria:
* DIPSS+ intermediate-2/high-risk MF with prior JAKi, \<20% blasts, and measurable spleen
* High-risk ET with platelets \>450×10⁹/L
* Resistant, refractory, intolerant, or has lost response to ≥1 prior line of therapy for MF and ≥2 prior lines for ET (unless only a single standard-of-care option is approved in the participating country)
* No prior stem cell transplant and none planned within 6 months
* Minimum Laboratory Requirements:
* Platelet count ≥50 × 10⁹/L
* Absolute neutrophil count ≥1 × 10⁹/L
* International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN), unless receiving vitamin K antagonists
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5 × ULN
* Total bilirubin \<2 × ULN
* Estimated creatinine clearance \>45 or \>30 mL/min (depending on study part)
Exclusion Criteria:
* Major bleeding or thrombosis (e.g., stroke, DVT, PE) within the past 3 months
* Active or high-risk HBV, HCV, or HIV infection, or other chronic active infections requiring systemic treatment
* Active invasive cancer within the past 2 years, except certain early-stage or low-risk cancers (e.g., resected skin, cervical, thyroid, or prostate cancer)
* Pregnant or unwilling to avoid pregnancy or fathering a child during the study and for a defined period after the last dose.
Other protocol-defined Inclusion/Exclusion Criteria may apply.
A Study With NKT5097 for Adults With Advanced/Metastatic Solid Tumors
The goal of this open-label dose escalation and expansion study is to evaluate the safety and tolerability of NKT5097 in adults with advanced/metastatic tumors (emphasis on breast cancer and solid tumors with CCNE1 amplification). Main questions to answer include:
* What is the recommended dose for expansion and/or Phase 2, for both monotherapy and in combination with ET
* What medical issues/symptoms do participants experience when taking NKT5097 as monotherapy as well as in combination with ET
* Able to provide written informed consent
* Advanced unresectable or metastatic solid tumor (Part 1, 2 \& 3 only)
* Advanced unresectable or metastatic HR+/HER2- breast cancer (Part 4 \& 5 only)
* Refractory to or unable to tolerate existing therapies (Part 1, 2 \& 4 only)
* Measurable or evaluable disease (Part 1, 2, \& 4 only).
* Measurable disease (Part 3 \& 5 only)
* Eighteen years of age or older
* ECOG status of 0 or 1
* Adequate organ function
* Patients with female reproductive organs must be surgically sterile, post- menopausal or willing to use effective contraception per protocol
* Patients who are capable of insemination must be willing to use highly effective contraception and to refrain from sperm donation during treatment and for 28 days after the last dose
* Able to swallow oral meds
* Willing to provide tumor tissue
Exclusion Criteria:
* Advanced solid tumor that is a candidate for curative treatment
* History of another malignancy except for the following: adequately treated local basal cell or squamous carcinoma of the skin, in situ cervical cancer, adequately treated papillary noninvasive bladder cancer, other adequately treated Stage I or Stage II cancers currently in complete remission
* Not recovered from the effects of prior anticancer therapy
* Clinically significant cardiovascular event, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 6 months
* Known active CNS metastases and/or carcinomatous meningitis
* Active interstitial lung disease requiring treatment
* History of uveitis, retinopathy, or other clinically significant retinal disease
* Major surgery within 30 days of administration of first dose
* Active uncontrolled infectious disease
* Significant liver disease (Child Pugh class B or C)
* Should not have received any prior selective investigational inhibitors or degraders (Part 5 only)
HR+ Breast Cancer, Triple Negative Breast Cancer (TNBC), CCNE1 Amplified Advanced Solid Tumors, HR+ HER2- Breast Cancer, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Liver, Lung/Thoracic, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Urinary, Ovary, Pancreas, Prostate, Small Intestine, Stomach, Urinary Bladder, Uterine (Endometrial)
CCNE1, cyclin E1, triple negative breast cancer, TNBC, estrogen receptor positive, HER2-, breast cancer, post CDK4/6i, HER2 expression, Fulvestrant, Letrozole, endocrine therapy, refractory, endocrine resistant, endocrine sensitivity, metastatic
Testing the Addition of Paclitaxel Administered Into the Abdominal Cavity Combined With Chemotherapy for Patients With Gastric Cancer Spread to the Abdominal Cavity (STOPGAP II)
This study is being done to answer the following questions:
Can we lower the chance of your gastric cancer from growing or spreading by administering paclitaxel chemotherapy directly into your abdominal cavity in addition to chemotherapy given through a vein in your arm? Will administering paclitaxel chemotherapy directly into your abdominal cavity, in addition to chemotherapy given through a vein in your arm help you live longer? We are doing this study because we want to find out if this approach is better or worse than the usual approach for your gastric cancer. The usual approach is defined as care most people get for gastric cancer.
If you decide to take part in this study, you will first receive a surgical procedure called a diagnostic laparoscopy. This will help the study doctors learn more about your gastric cancer. Laparoscopy is a minimally invasive surgery for which you will be placed under general anesthesia. Then the surgeon will make small incisions (5mm) on your belly through which a camera and thin instruments are introduced to evaluate the abdomen. This procedure takes about 1 hour to complete. Your study group will be assigned during the surgery. The study groups are described further in the 'What are the study groups?' section below.
If you are placed into the study group 1, you will not have an intraperitoneal port (a small device which is placed under the skin and fat of your upper abdomen and a tube that is placed into the abdomen).
If you are placed into the study group 2, you will have an intraperitoneal port placed. The reason is that in addition to standard chemotherapy, which is given through a vein in your arm, this port will be used to deliver the medication paclitaxel directly inside your abdomen when you are ready to start study treatment.
It is important to know that you will not know your study group until after the surgery is over. This is because information that is learned during the surgery will help determine which study group you are put in.
Once you have fully healed from this surgery, you will start study treatment. Depending on which study group you are assigned, you will either receive a standard chemotherapy regimen (the regimen will be chosen by you and your doctor) if you are in study group 1, or paclitaxel through a tube in your belly plus chemotherapy given through a vein in your arm if you are in study group 2. All participants will get treatment for three (3) months after which you will undergo reevaluation. If the disease is under control or responding to treatment, you may continue the assigned treatment until your disease gets worse, the side effects become too severe, or you may be offered a surgical procedure to remove the cancer if the amount of disease is low and can be completely removed as determined by a surgeon.
There is a very small chance that during the laparoscopy surgical procedure, the doctor might find something called "intra-abdominal adhesions". These are areas where the stomach has healed previously and created scar tissue. If this scar tissue prevents the surgeon from being able to place a port in the correct area, you would be ineligible to receive the study treatment. If this happens, you may still receive standard of care therapy after your surgery, but you will not be able to continue on the study. If you have more questions about this, you can ask your surgeon or the study team to help.
After you finish your study treatment, your doctor or study team will watch you for side effects. They will continue to follow your condition every three (3) months during the first two (2) years, then every six (6) months until year 5. You may be reevaluated with Chest/Abdomen/Pelvis scans every three-six (3-6) months for up to five (5) years if decided by your doctor.
STEP 0 REGISTRATION:
* Patient must be at least 18 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Patient must have histologically or cytologically confirmed microsatellite stable (MSS) or mismatch repair (MMR) protein expression proficient primary gastric or gastroesophageal adenocarcinoma (Siewert 3) with synchronous cytology positive disease (cyt+) OR peritoneal carcinomatosis detected by imaging, laparoscopy or laparotomy. Patients with microsatellite instability-high (MSI-H/dMMR) mismatch repair deficient disease are not eligible
* Patient must have received a minimum of 3 months and a maximum of 6 months of first line systemic treatment
* Patient must be registered to Step 0 within 4 weeks of the last dose of first line systemic therapy. Patient must not have any ongoing significant adverse events that would prohibit them from undergoing a diagnostic laparoscopy procedure followed by further systemic and intraperitoneal therapy
* Patient must have no evidence of small or large bowel obstruction other than gastric outlet obstruction due to primary malignancy
* Patient must have no evidence of solid organ metastases except for ovarian metastases. Baseline imaging must be done within 30 days prior to Step 0 registration
* Patient must have no evidence of clinically significant radiologic peritoneal disease progression during first line systemic therapy
* Patient must have no evidence of extensive retroperitoneal lymph node metastases not amenable to resection during gastrectomy
* Patient must have no history of prior surgery that would preclude safe diagnostic laparoscopy and port placement
* Patient must have no evidence of massive ascites on imaging or history of two therapeutic paracentesis with drainage of more than 1.0 liter of ascites each time in 30 days prior to Step 0 registration
* 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 II or better
* Patient must not have any uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous
* Patient must not have any known contraindications or drug allergies to the protocol treatment agents: paclitaxel, 5-fluorouracil, or leucovorin
* Leukocytes ≥ 2,000/uL (≤ 30 days prior to Step 0 registration)
* Absolute neutrophil count (ANC) ≥ 1,500/uL (≤ 30 days prior to Step 0 registration)
* Platelets ≥ 75,000/uL (≤ 30 days prior to Step 0 registration)
* Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). If patient has Gilbert's syndrome, total bilirubin must be \< 2.0 mg/dL (≤ 30 days prior to Step 0 registration)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 x institutional ULN (≤ 30 days prior to Step 0 registration)
* Creatinine clearance ≥ 30 mL/min (estimated using Cockcroft and Gault formula or measured) (≤ 30 days prior to Step 0 registration)
* Hemoglobin ≥ 8 g/dL (≤ 30 days prior to Step 0 registration)
* Serum albumin ≥ 2.5 g/dL (≤ 30 days prior to Step 0 registration)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 0 registration are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* 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
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
* All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 0 registration to rule out pregnancy
* A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception (or by abstaining from sexual intercourse) for the duration of their participation in the study. Arm A patients must adhere to the contraceptive requirements outlined in the product specific package inserts while on protocol treatment. Arm B patients must continue contraceptive measures for at least 3 months after the last dose of protocol treatment. In addition, both Arm A and Arm B patients who continue with targeted agents must adhere to the contraceptive requirements outlined in the product specific package inserts while on protocol treatment
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
STEP 1 RANDOMIZATION:
* Patient must have undergone a diagnostic laparoscopy with peritoneal lavage performed and aspiration for cytology obtained
* The extent of peritoneal disease burden must have been assessed during the diagnostic laparoscopy with the Peritoneal Cancer Index (PCI) available
* Patient must not have extensive intraabdominal adhesions that preclude safe placement of the intraperitoneal port
DRUG: Standard of Care Chemotherapy, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Diagnostic Laparoscopy, PROCEDURE: Intraperitoneal Port Placement, PROCEDURE: Magnetic Resonance Imaging, DRUG: Intraperitoneal Paclitaxel
ASPEN-09-03: A Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Metastatic HER2-Positive Breast Cancer (ASPEN-09-03)
The Substudy Protocol ASPEN-09-03 is a Phase 2, single-arm, multicenter study evaluating the efficacy, safety, and tolerability of evorpacept in combination with trastuzumab and chemotherapy in participants with HER2-positive metastatic breast cancer who have previously received trastuzumab-deruxtecan. This substudy is actively recruiting.
ASPEN-09-03 is a substudy under Master Protocol ASPEN-09, and additional substudies are as follows:
* Metastatic colorectal cancer (CRC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open.
* Recurrent/metastatic head and neck cancer (HNSCC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open.
* Histologically confirmed invasive HER2+ breast cancer based on an evaluable tumor tissue biopsy obtained after cessation of T-DXd (ENHERTU) treatment and no more than 6 months prior to C1D1.
* Received no more than 4 prior lines of HER2-directed therapy including at least one prior line of T-DXd (ENHERTU) for locally advanced/metastatic HER2+ breast cancer. Prior neoadjuvant therapy which resulted in relapse within 6 months of completion of T-DXd will be considered a line of treatment for metastatic disease. Participants who discontinue T-DXd due to intolerance are considered eligible.
* Progressed on or following the most recent line of therapy.
* Eligible to receive one of the following chemotherapy options (capecitabine, eribulin, gemcitabine, paclitaxel or vinorelbine).
* Measurable disease as defined by RECIST v1.1.
* LVEF ≥50%.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 to 1.
* Life expectancy of at least 3 months.
* Adequate renal function (estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
* Adequate liver function:
* Total bilirubin ≤1.5 x upper limit of normal (ULN) (≤3.0 x ULN if the participant has documented Gilbert syndrome);
* Aspartate and alanine transaminase (AST and ALT) ≤3 x ULN (≤5.0 x ULN if liver involved by metastatic disease).
* Participants must have recovered from all AEs due to previous therapies, procedures, and surgeries to baseline severity or ≤Grade 1 per NCI CTCAE v5.0 except for AEs not deemed reversible and which do not constitute a safety risk by Investigator judgment.
Exclusion Criteria:
* Untreated CNS metastases.
* Prior exposure to any anti-CD47 or anti-SIRPα agent.
* Any condition that would be contraindicated to receiving trastuzumab
* Has a diagnosis of complete dihydropyrimidine dehydrogenase (DPD) deficiency or significant toxicity with prior flurouracil (5FU) based regimen
* Following anti-cancer therapy with insufficient washout before start of treatment:
• chemotherapy, hormonal therapy, radiation therapy or small molecule anti-cancer therapy within 14 days or 5 half-lives (whichever is shorter) of start of treatment.
• Immune therapy or other biologic therapy (e.g., monoclonal antibodies, antibody-drug conjugates) for the treatment of cancer for: 28 days or 5 half-lives (whichever is shorter) of start of treatment).
* History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction.
* Had an allogeneic tissue/solid organ transplant.
* Any active, unstable cardiovascular disease.
* Intolerance to or who have had a severe allergic or anaphylactic reaction to antibodies or infused therapeutic proteins or participants who have had a severe allergic or anaphylactic reaction to any of the substances included in the study drug (including excipients).
* Has an active autoimmune disease that has required systemic treatment in past 2 years.
* Other primary malignancy within 2 years.
A Clinical Study of Calderasib (MK-1084) With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)
Researchers are looking for other ways to treat locally advanced or metastatic colorectal cancer (mCRC) that is unresectable and has a gene mutation called KRAS G12C.
Standard (or usual) treatments for this type of colorectal cancer may include mFOLFOX6 with or without bevacizumab. Researchers want to learn if adding calderasib (the study medicine) and cetuximab to mFOLFOX6 can treat locally advanced or mCRC with the KRAS G12C mutation. Calderasib and cetuximab are targeted therapies.
The goals of this study are to learn:
* About the safety of calderasib with cetuximab and mFOLFOX6 and if people tolerate the treatments
* If people who receive calderasib with cetuximab and mFOLFOX6 live longer without mCRC growing or spreading compared to people who receive mFOLFOX6 with or without bevacizumab.
The main inclusion criteria include but are not limited to the following:
* Has a histologically confirmed diagnosis of locally advanced unresectable or metastatic (unresectable Stage III or Stage IV as defined by American Joint Committee on Cancer \[AJCC\] eighth edition) colorectal adenocarcinoma
* Part 2 only: Has not received systemic anticancer therapy for locally advanced unresectable or metastatic colorectal cancer; an exception is permitted for 1-2 cycles of FOLFOX or 1 cycle of CAPOX as optional chemotherapy before or during the screening period
* Demonstrates presence of a Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
* Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has known partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization, with the exception of the optional chemotherapy
* Has 1 or more conditions that, in the opinion of the investigator, make the participant ineligible for treatment with bevacizumab
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease
* Has active infection requiring systemic therapy
* Has not adequately recovered from major surgery or have ongoing surgical complications
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer (ReDiscover-2)
This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 (zovegalisib) + fulvestrant to capivasertib + fulvestrant for the treatment of patients with HR+/HER2- ABC with PIK3CA mutation following recurrence or progression on or after treatment with a CDK4/6 inhibitor.
* Patient has ECOG performance status of 0-1
* One or more known primary oncogenic PIK3CA mutation(s)
* Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with a gonadotropin-releasing hormone (GnRH) agonist. Patients are to have commenced treatment with a GnRH agonist at least 2 weeks prior to randomization and must be willing to continue on it for the duration of the study.
* Histologically or cytologically confirmed diagnosis of HR+/HER2- locally advanced or metastatic breast cancer (ABC) with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent
* Measurable disease per RECIST v1.1 or evaluable bone-only disease.
* Must have radiological evidence of progression on or after previous treatment for HR+/HER2- ABC with:
• At least 1 and no more than 2 lines of endocrine therapy (ET) in the (neo)adjuvant setting with recurrence on or within 12 months of completion or in the ABC setting
• Only 1 prior line of CDK4/6 inhibitor therapy in one of the following settings:
• CDK4/6 inhibitor + ET in the ABC setting
• CDK4/6 inhibitor therapy in the adjuvant setting if progression occurred during or within 12 months of completion of adjuvant CDK4/6 inhibitor with ET
• Patients who progressed during or within 12 months of completion of adjuvant CDK4/6 inhibitor and after receiving CDK4/6 inhibitor therapy in the advanced setting are considered to have had \>1 prior line of CDK4/6 inhibitor and are not eligible
Exclusion Criteria:
* Prior treatment with any of the following:
• CDK2 inhibitors. Prior treatment with other investigational CDK inhibitors could be permitted upon discussion and approval from the Sponsor
• PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway
• Immunotherapy
• Antibody drug conjugates
* Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥ 140 mg/dL (7.8 mmol/L), or glycosylated hemoglobin (HbA1c) ≥7.0% (≥ 53 mmol/mol).
* Clinically significant, uncontrolled cardiovascular disease
* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
* Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control
* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
* History of hypersensitivity to fulvestrant or drugs in a similar class as fulvestrant, zovegalisib, or capivasertib, including their excipients
* Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K
PIK3CA Mutation, HER2- Negative Breast Cancer, Hormone Receptor Positive Tumor, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, Breast - Female, Breast - Male
UT Southwestern; Parkland Health & Hospital System
A Study to Learn About the Medicine Ponsegromab in Adults With Cancer of the Pancreas Which Has Spread and Caused Significant Body Weight Loss and Fatigue
Study to investigate the efficacy, safety and tolerability of systemic chemotherapy plus ponsegromab versus systemic chemotherapy plus placebo for the first-line treatment in adult participants with cachexia and metastatic pancreatic ductal adenocardinoma.
Key inclusion Criteria:
* Signed Informed Consent Document
* Documented active diagnosis of metastatic pancreatic ductal adenocarcinoma
* Cachexia defined by Fearon criteria of weight loss
* Completed 1 x 28-day cycle of first-line systemic nab-paclitaxel and gemcitabine chemotherapy or 2 x 14-day cycles of FOLFIRINOX chemotherapy and prior to receiving Cycle 2 chemotherapy
* ECOG PS ≤1 with life expectancy of at least 4 months
Key
Exclusion Criteria:
* Current active reversible causes of decreased food intake
* Cachexia caused by other reasons
* Any prior or current clinical diagnosis of heart failure, irrespective of left ventricular ejection fraction or New York Heart Association classification
* Left ventricular ejection fraction \<50%
* Receiving tube feedings or parenteral nutrition at the time of Screening or Randomization
* History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody
* History of allergy or hypersensitivity to any of the chemotherapeutics or any of their excipients
* Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma, symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases
* Inadequate liver function
* Renal disease requiring dialysis or eGFR \<30 mL/min/1.73m2
A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032)
Researchers are looking for new ways to treat types of breast cancer that are both:
* High-risk, which means the cancer may have a higher chance of getting worse or coming back after treatment
* Early-stage, which means the cancer is in the breast or the lymph nodes around the breast The 2 types of breast cancer in this study are triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer. These cancers have zero or a low amount of a protein called HER2 and other proteins that attach to the hormones estrogen or progesterone.
Sacituzumab tirumotecan (also known as sac-TMT or MK-2870), the study medicine, is a type of targeted therapy. A targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread.
The main goals of this study are to learn if people who receive sac-TMT, pembrolizumab, and chemotherapy:
* Have fewer cancer cells found in the tumors and lymph nodes removed during surgery compared to those who receive only pembrolizumab and chemotherapy
* Live longer without the cancer growing, spreading, or coming back compared to people who receive only pembrolizumab with chemotherapy
The main inclusion criteria include but are not limited to the following:
* Has previously untreated high-risk, early-stage, non-metastatic (M0) breast cancer (BC), defined as any of the following combined primary tumor (T) and regional lymph node (N) staging per AJCC 8th edition criteria as assessed by the physician investigator based on radiological and/or clinical assessment:
* cT1c, N1-N2
* cT2, N0-N2
* cT3, N0-N2
* cT4a-d, N0-N2
* The participant must have a centrally confirmed diagnosis of BC that is triple-negative or HR-low+/HER2- (defined as estrogen receptor (ER)-low+ expression in 1% to 10% cells and HER2- as by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
* Provides a core needle biopsy from the primary breast tumor at screening to the central laboratory.
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 28 days before Cycle1 Day 1 (C1D1).
* Demonstrates adequate organ function.
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Metastatic (Stage IV) breast cancer or clinical node stage 3 (cN3) nodal involvement
* Has received any prior treatment, including radiation, systemic therapy,and/or definitive surgery for currently diagnosed breast cancer
* Has undergone excisional biopsy of the primary tumor, axillary lymph node dissection, and/or axillary sentinel lymph node biopsy prior to study treatment.
* Received prior systemic anticancer therapy including investigational agents within 4 weeks before C1D1.
* Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX- 40, CD137).
* Received prior treatment with a TROP2-targeted antibody-drug conjugate (ADC).
* Received prior treatment with a topoisomerase I inhibitor-containing ADC.
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Known additional malignancy that is progressing or has required active treatment within the past 5 years.
* Uncontrolled systemic disease.
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids, has current pneumonitis/interstitial lung disease or has suspected interstitial lung disease (ILD) or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening..
Recovery Through Inspiration, Support, and Empowerment (RISE)
The goal of this pilot study is to test the effectiveness of a novel intervention for young adults (ages 18-27) with mental health conditions who have been released from an acute care psychiatric facility. The intervention aims to reduce suicidality, depression, anxiety, re-hospitalization, and improve mental health recovery by using outpatient services.
The current standard of care (SOC) for these patients at discharge includes a discharge plan with a list of their medications, anticipated outpatient appointments, and information on when and where to find community resources.
The intervention being tested involves the implementation of a mental health recovery education and support program, involving one-on-one and small group meetings led by Peer Support Specialists (PSS) and Recovery Community Organizations (RCO).
Participants will be assigned to either Cohort A or B for 8 weeks.
Cohort A will be the intervention group with PSS and RCOs.
* Weeks 1-4: One-on-one meetings with PSS for education and support. Assessments will be completed at weeks 2 and 4.
* Weeks 5 and 7: One-on-one meetings with PSS for education and support.
* Week 6 and 8: Group meetings with PSS and other participants from RCOs. Assessments will be completed during these weeks.
Cohort B will be the SOC group with no PSS or RCOs.
* Weeks 1-4: Weekly check in phone calls with a member of the research team. Assessments will be completed at weeks 2 and 4.
* Weeks 5-8: Check in phone calls with a member of the research team every other week. Assessments will be completed at weeks 6 and 8.
Data collected from participant assessments, adherence to medication, and re-admittance to a psychiatric facility will be used to compare the intervention to the SOC.
* Chief complaint of suicidal ideation, suicide attempt, depression, and/or anxiety
* discharged from inpatient care or from emergency department
* men and women ages 18-27
Exclusion Criteria:
* primary diagnosis of: substance use disorder, schizophrenia spectrum, intellectual development disorder, autism spectrum disorder (level II or III)
Peer Support Specialist (PSS), Recovery Community Organization (RCO), Mental Health Recovery, Transitional Age Youth (TAY), UT Southwestern Medical Center, Young Adult
Testing Higher Dose Radiation Therapy for Locally Advanced Pancreatic Cancer (LAP100)
This phase III trial compares the effect of dose-escalated radiation therapy to usual care in patients with locally advanced unresectable pancreatic ductal adenocarcinoma who have received an initial 4-8 months of chemotherapy. Usual care options include additional chemotherapy, observation, or standard lower-dose radiation therapy. These treatments may delay tumor growth but have not been shown to improve survival. Radiation therapy uses high energy X-rays to kill cancer cells and shrink tumors. Dose-escalated radiation therapy involves the precise delivery of higher doses to the tumor, often over a shorter period of time. This trial assesses whether using dose-escalated radiation therapy can prolong survival.
* At time of enrollment, the patient must have received 4-8 months of active chemotherapy with FOLFIRINOX or NALIRIFOX or gemcitabine/nab-paclitaxel. Patients are permitted to receive more than 1 type of chemotherapy for reasons other than radiographic progression by Response Evaluation Criteria in Solid Tumors (RECIST) (i.e. chemotherapy regimen switch is allowed for toxicity, and/or switch is allowed for toxicity and/or CA19-9 level not declining). Patients are allowed to receive chemotherapy after restaging scans, as long as 1) restaging scans are performed after at least 4 months of chemotherapy and 2) the total chemotherapy duration does not exceed 8 months
* "Active chemotherapy" refers to time on chemotherapy not counting treatment breaks (i.e. if a patient had 1 month of chemotherapy followed by 1 month break, this would count as 1 month chemotherapy). Study registration must occur within 45 days of last day of pre-study entry chemotherapy
* BASELINE PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
* Pathologically (histologically or cytologically) proven diagnosis of pancreatic ductal adenocarcinoma
* Locally advanced unresectable disease (as defined per the National Comprehensive Cancer Network \[NCCN\] guidelines and institutional tumor board review)
* Patients must have baseline pre-chemotherapy scans for staging. Options include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, CT chest/CT pelvis/MRI abdomen, or PET/CT performed prior to enrollment
* Age ≥ 18 years
* Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
* Required initial laboratory values:
All laboratory values must be obtained any time prior to initiation of chemotherapy up to 30 days post initiation of chemotherapy
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN)
* BASELINE CA19-9 AND BILIRUBIN REQUIREMENTS: The purpose is to obtain a baseline CA19-9 in the setting of a normal (or close to normal) bilirubin, since serologic response by serial CA19-9 measurements is part of post-chemotherapy eligibility criteria
* If baseline CA19-9 \> 37 U/mL the concurrent bilirubin must be ≤ 1.5 x ULN. (Note: if the bilirubin is not ≤ 1.5 x ULN both the CA19-9 and concurrent bilirubin can be repeated until bilirubin is ≤ 1.5 x ULN, as long as done within specified timeframe \[up to 30 days post chemotherapy initiation\])
* If baseline CA19-9 U/mL ≤ 37, there are no restrictions on the required concurrent bilirubin level, and this can be the accepted baseline value
* Prior radiation treatment
* Has the patient had prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Prior non-overlapping radiation (e.g., breast, head and neck, extremity) is permitted
* If uncertain about prior overlap, please contact the study principal investigator, Dr. Nina Sanford
* POST PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
* If baseline CA19-9 is elevated (defined as \> 37 u/mL) the post-pre-entry chemotherapy CA19-9 must be less than 200 u/mL OR a 70% decline from pre-chemotherapy level (i.e. a patient with post induction chemotherapy CA199 value ≥ 200 u/mL would qualify, as long as they had at least 70% drop from baseline CA199 value; similarly, a patient with less than a 70% decline would qualify as long as absolute value post induction chemotherapy is under 200 u/mL) (must be completed any time post month 4 of chemotherapy and prior to study entry)
* If baseline CA19-9 is not elevated (defined as ≤ 37 u/mL) the post-pre-entry chemotherapy CA19-9 must remain ≤ 37 u/mL (must be completed any time post month 4 of chemotherapy and prior to study entry)
* No active duodenal or gastric ulcers
* No direct tumor invasion of the bowel or stomach
* Restaging scans showing at least stable disease (no progression). Options for scans include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen, or PET/CT performed prior to enrollment, with restaging CT showing at least stable disease
* Not pregnant and not nursing
* No cardiac condition that was the primary reason for hospitalization in the last 6 months
* New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: 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.)
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Locally Advanced Unresectable Pancreatic Ductal Adenocarcinoma, Stage II Pancreatic Cancer AJCC v8, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, Pancreas
UT Southwestern; Parkland Health & Hospital System
A Study to Assess Adverse Events and Change in Disease Activity of Oral Surzetoclax Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM)
Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the safety and change in disease activity of surzetoclax in adult participants with relapsed/refractory (R/R) MM. Adverse events and change in disease activity will be assessed.
Surzetoclax is an investigational drug being developed for the treatment of R/R MM. In Substudy 1 there will be dose escalation and dose expansion phases where participants will receive various doses (escalation) or 1 of 2 doses (expansion) of surzetoclax in combination with daratumumab + dexamethasone, to determine the best dose of surzetoclax. In Substudy 2, there will be a dose escalation phase where participants will receive various doses of surzetoclax alone. In Substudy 3 there will be dose escalation and optimization phases where participants will receive various doses (escalation) or 1 of 2 doses (optimization) of of surzetoclax and etentamig to determine the best dose of surzetoclax and etentamig. Optimization will also include etentamig received alone. Approximately 325 adult participants with R/R MM will be enrolled in the study in approximately 55 sites worldwide.
In Substudy 1 escalation phase, participants will receive oral surzetoclax tablets in combination with subcutaneous (SC) daratumumab injections + oral dexamethasone tablets and in the expansion phase, will receive 1 of 2 doses oral surzetoclax tablets in combination with SC daratumumab injections + oral dexamethasone tablets or daratumumab injections + oral pomalidomide + oral dexamethasone tablets. In Substudy 2, Japanese participants will receive oral surzetoclax tablets. In Substudy 3 escalation phase, participants will receive oral surzetoclax tablets in combination with IV etentamig and in the expansion phase, will receive 1 of 2 doses of both oral surzetoclax tablets in combination with of IV etentamig, or IV etentamig alone. The total study duration is approximately 4.5 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution. The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.
* Documented diagnosis of multiple myeloma (MM) based on standard international myeloma working group (IMWG) diagnostic criteria.
* All participants must have measurable disease per central laboratory with at least 1 of the following assessed within 28 days prior to enrollment:
* Serum M-protein \>= 0.5 g/dL (\>= 5g/L); OR
* Urine M-protein \>= 200 mg/24 hours; OR
* For participants without measurable serum and urine M-protein: Serum free light chain (sFLC) \>= 10 mg/dL (100 mg/L), provided sFLC ratio is abnormal.
* B-cell lymphoma (BCL)-2 inhibitor treatment naïve.
* t(11;14) positive status and/or BCL2 high status.
* Must have confirmed diagnosis of relapsed or refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen, based on the investigator's determination of the international myeloma working group (IMWG) 2016 criteria.
Exclusion Criteria:
* Major surgery within 4 weeks of study treatment or planned during study participation.
* Recent infection requiring systemic treatment that was completed \<= 14 days before first dose of study treatment and/or uncontrolled active systemic infection.
A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy (OPAL)
This double-blind, Phase 2, multiple-dose study will be conducted to evaluate the PK/PD, efficacy, safety, and tolerability of apitegromab in subjects \<2 years old with 5q autosomal recessive SMA who have delayed motor milestones for their age attributed to SMA at the discretion of the Investigator or a Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score \<55.
• Is \<2 years old at the time of the informed consent
• Had a gestational age of ≥35 weeks and gestational body weight ≥2.0 kg at birth
• Has confirmed diagnosis of 5q autosomal recessive SMA
• Has confirmed presence of SMN2 gene copy(ies)
• Must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam)
• Body weight for age is no less than 1st percentile based on the WHO Child Growth Standards at the Screening Visit
• Has delayed motor milestones for age attributed to SMA at the discretion of the Investigator or a CHOP-INTEND score \<55
Exclusion Criteria:
• Nutritional status that is not anticipated to be stable throughout the study or medical necessity for a gastric feeding tube, where most feeds are administered by this route
• Major orthopedic issues such as severe scoliosis or severe contractures or interventional procedure, including spine or hip surgery, which is considered to have the potential to substantially limit the ability of the subject to be evaluated on any motor function outcome measures, within 6 months before Screening or anticipated during the study
• Any other physical limitations (eg, the subject requires cast for contractures) that would prevent the subject from undergoing motor function outcome measures throughout the study.
This Study Will Explore Whether a Combination of the Investigational Drug Mevrometostat (PF-06821497) and Enzalutamide Will Work Better Than Taking Enzalutamide Alone in Participants With mCSPC Who Are ARPI naïve.
This study will explore whether a combination of the investigational drug mevrometostat (PF-06821497) and enzalutamide will work better than taking enzalutamide alone in participants with mCSPC who are ARPI naïve and have not yet received chemotherapy in the mCSPC setting.
Inclusion Criteria
* Male participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening.
* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
* Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesion(s) on CT or MRI (for soft tissue/visceral disease).
* Resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1 (except for AEs which do not constitute a safety risk in the investigator's judgement).
* Participants must have ECOG PS 0 or 1.
Exclusion Criteria
* Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
* Clinically significant cardiovascular disease.
* Known or suspected brain metastasis or active leptomeningeal disease.
* Participants must be treatment naïve at the mCSPC stage, eg, participants cannot have received any cytotoxic chemotherapy with the following exceptions: Treatment with first-generation antiandrogen (ADT) agents is allowed for mCSPC.
* Previous administration with an investigational product (drug or vaccine) within 30 days.
* Use of 5-alpha reductase inhibitors is prohibited within 28 days of randomization.
* Prior surgery from which the participant has not fully recovered at least 28 days prior to randomization
* Current use or anticipated need for drugs that are known strong CYP3A4/5 inhibitors and inducers (with exception of enzalutamide as part of this study).
* Inadequate organ function.
* Known allergic or hypersensitivity reactions to mevrometostat or its excipients or to enzalutamide or its excipients.
Ocular Assessments in Patients Treated With Tivdak® in Recurrent or Metastatic Cervical Cancer
TIVDAK is used for the treatment of cervical cancer that has come back after chemotherapy. Chemotherapy is a treatment that uses medicines to stop the growth of cancer cells. This is done either by killing the cells or by stopping them from growing. The purpose of this study is to learn about possible side effects of TIVDAK, specially to any side effect that is related to the eye. A side effect is anything a medicine does to your body that is not part of how the medicine treats disease.
* This study is seeking for participants who: Are willing to take all the required eye tests
* Have not received TIVDAK before
* Do not have any active eye issues.
Participants will receive TIVDAK once every 3 weeks as an infusion that will be injected into the vein. Participants will visit an eye care provider at 3 stages:
* before starting the treatment,
* before each of the first 9 infusions
* then monthly for 3 months after they stop taking TIVDAK. Treatment with TIVDAK will continue until it is not working anymore against the participant's cancer.
Inclusion criteria:
• Must have recurrent or metastatic cervical cancer with disease progression on or after chemotherapy
• Treating physician has determined that treatment with Tivdak is appropriate for the participant according to US Prescribing Information
• Must sign an informed consent form indicating that the participant understands the purpose and procedures required for the study and are willing to participate
• Must be willing to undergo repeated ocular assessments as required by the study and regular clinic visits according to local standard practice of the study site
• Must agree to use effective contraception according to the US Prescribing Information
Exclusion criteria:
• Active ocular disease at baseline per investigator assessment
• Previous treatment with Tivdak
• Previous administration of an investigational drug within 30 days
• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may, in the investigator'
A Trial of D-mannose for the Prophylaxis of Recurrent Urinary Tract Infections (DmannoseRCT)
A randomized, double-blind, placebo-controlled, 12-month study to determine the effectiveness of D-mannose (2g daily) supplementation in rUTI (recurrent urinary tract infection) prevention in post-menopausal women.
* Female, post-menopausal, age ≥ 55 years old
* Diagnosis of recurrent UTI, defined as ≥ 3 symptomatic culture-proven UTI episodes in 12 months or ≥ 2 in 6 months.
* Currently free from a UTI determined based on absence of symptoms as determined by the UTI symptom assessment questionnaire79 and negative urine culture (\<103 colony forming units per ml of urine).
* Able to attend all follow-up appointments for the study.
* A negative upper and lower urinary tract evaluation, including pelvic examination for pelvic organ prolapse (less than stage 2), measurement of post-void residual (less than 50 ml), and imaging (renal ultrasound and standing voiding cystourethrogram) to exclude kidney stone, hydronephrosis, reflux, or urethral diverticulum.
Exclusion Criteria:
* Current use of D-mannose. Patients willing to stop taking D-mannose will be offered to join the trial after a 4-week wash-out period.
* Complicated UTIs, including need for catheter drainage or intermittent catheterization, neurogenic bladder, bladder augmentation, or urinary diversion.
* Ongoing supplement use (Box 1). Patients willing to stop taking the listed supplements will be offered to join the trial after a 4-week wash-out period.
* Evidence of upper tract infection (pyelonephritis), including temperature higher than 38°C, flank/lumbar pain or tenderness
* Diagnosis of interstitial cystitis or overactive bladder syndrome
* Prophylactic antibiotics started in the last 3 months and unwilling to discontinue, or intention to start in the next 12 months
* Use of Uromune or other vaccine approaches to reduce rUTI
* Participation in a research study involving an investigational product in the past 12 weeks
* Receipt of phage treatment
* History of chronic diarrhea requiring regular therapy
* Inability to swallow or known history of gastrointestinal malabsorption
* History of recurrent vaginal yeast infections
* Systemic disease precluding enrollment in this study (uncontrolled diabetes with HgA1C above 7, ongoing chemotherapy or immunotherapy, renal insufficiency \[creatinine \> 1.5 g/dl\]), mental or cognitive impairment, weight loss diet requiring excessively large amounts of fluid intake, or other health-related specific diet).
* Nursing home resident
* BMI \>40
Box 1 Supplements to avoid
* Multi-Vitamins and Multi-Mineral capsules
* Specific Vitamins or Minerals (e.g., Calcium, Citrical, Calcium Gummies, Vitamin A, D, Niacin, Pyridoxine, Selenium, Vitamin E, B6, Iron, Omega 3, D3, Magnesium, B-Complex, Women's Ultra MultiVitamin, GNC B-Complex, B-12, PreserVision Areds2, Vitamins D, B Pollen)
* Probiotics
* Cranberry Mannose or Cranberry Extract Weight loss products to avoid
* Medifast
* Vitafusion
* OptiVin Products
* Appetite Suppressants
* Keto-Fuel
Testing the Addition of Docetaxel (Chemotherapy) to the Usual Treatment (Hormonal Therapy and Apalutamide) for Metastatic Prostate Cancer, ASPIRE Trial
This phase III trial compares the effect of adding docetaxel to hormonal therapy and apalutamide versus hormonal therapy and apalutamide alone in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Hormone therapy for prostate cancer, also called androgen deprivation therapy (ADT), uses surgery or drugs to lower the levels of male sex hormones in a man's body. This helps slow the growth of prostate cancer. Apalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Giving docetaxel in addition to the usual treatment of hormonal therapy and apalutamide may work better in treating patients with metastatic prostate cancer than the usual treatment alone.
* Documentation of disease:
\* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology
* Must have had evidence of metastatic disease (American Joint Committee on Cancer \[AJCC\] metastasis \[M\]1 disease) based on conventional CT/MRI and/or bone scan. This will be defined as:
* Bone metastases detected by CT, radionuclide technetium-99 (99Tc)- methylene bisphosphonate bone scan, or MRI as defined by PCWG3 criteria; OR
* Non-pelvic lymph node metastases (measurable lymph nodes above the aortic bifurcation; lymph nodes are measurable if the short axis diameter is ≥ 15 mm) detected on CT or MRI as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Subjects with regional lymph node metastases only (nodes \[N\]1, below the aortic bifurcation) will not be eligible for the study; OR
* Visceral or soft tissue metastases detected on CT or MRI as defined by RECIST version 1.1. Soft tissue/visceral lesions are measurable if the long axis diameter is ≥ 10 mm
* Evidence of metastatic disease by PSMA-PET only and not visible by CT, radionuclide bone scan, or MRI will not satisfy eligibility criteria
* No metachronous low-volume disease (defined as recurrent metastatic disease after definitive treatment of prostate primary) and with ≤ 4 bone metastasis and no visceral metastasis on conventional imaging by CT, radionuclide 99Tc-biphosphonate bone scan, or MRI)
* Next generation sequencing (NGS) results from any tissue based Clinical Laboratory Improvement Act (CLIA) test must be available at the time of registration. NGS from soft tissue or visceral lesion if available is preferred. NGS from bone or primary prostate will be accepted. Patients with failed NGS testing are not eligible
* Prior treatment
* ADT (luteinizing hormone-releasing hormone \[LHRH\] agonist/antagonist or orchiectomy) with or without first generation anti-androgen, or second-generation androgen receptor signaling inhibitor (ARSI) within 120 days of registration is permitted. No washout period will be needed for the first generation- androgen or ARSI prior to registration. Anti-androgen treatment is only permitted if used within 120 days of registration
* No prior chemotherapy for prostate cancer
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
* Hemoglobin ≥ 9.0 g/dL
* Platelet count ≥ 100,000/mm\^3
* Total bilirubin ≤ 1 x upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1 × ULN, subject may be eligible)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate transaminase \[SGT\]) ≤ 1.5 x upper limit of normal (ULN)
* Calculated (Calc.) creatinine clearance \> 30 mL/min
* Serum potassium ≥ 3.5 mmol/L
* Comorbid conditions
* 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
* Leptomeningeal metastases: Patients with treated leptomeningeal metastases are eligible if follow-up brain imaging 30 days after central nervous system (CNS)-directed therapy shows no evidence of progression
* HIV: Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
* Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* No seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation or condition requiring CNS surgery or radiation therapy)
* 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 II or better. Any condition that in the opinion of the investigator, would preclude participation in this study. Patients with stable asymptomatic deep venous thromboembolism on stable anti-coagulation will be eligible
* Hypertension: Subjects with uncontrolled hypertension as indicated by a resting systolic blood pressure (BP) \>= 160 mmHg or diastolic BP \>= 100 mmHg despite medical management are not permitted to register
* Allergies: Subjects with known hypersensitivity to any of the study drugs, or excipients in the formulation of the study drugs are not permitted to register
* Concomitant medications
* Chronic concomitant treatment with strong inhibitors of cytochrome P450 3A4 (CYP3A4) is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration on the study. See Section 8.1.9 for more information
* Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
* Medications known to lower the seizure threshold must be discontinued or substituted prior to study entry. See Section 8.1.9 for more information
* Patient agrees to use a condom (even men with vasectomies) and another effective method of birth control if having sex with a woman of childbearing potential or agrees to use a condom if having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug
DRUG: Androgen Therapy, DRUG: Apalutamide, DRUG: Docetaxel, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Bone Scan, PROCEDURE: PSMA PET Scan, PROCEDURE: Biospecimen Collection, OTHER: Questionnaire Administration
A Clinical Study of Ifinatamab Deruxtecan (I-DXd) in People With Metastatic Prostate Cancer (MK-2400-001)
Researchers are looking for new ways to treat metastatic castration-resistant prostate cancer (mCRPC). Researchers have designed a study medicine called ifinatamab deruxtecan (also called I-DXd or MK-2400) to treat mCRPC. The goal of this study is to learn if people who receive I-DXd live longer overall and live longer without the cancer growing or spreading than people who receive chemotherapy.
The main inclusion criteria include but are not limited to the following:
* Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
* Has prostate cancer progression while on androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months prior to Screening
* Has current evidence of distant metastatic disease (M1 disease) documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography (CT)/magnetic resonance imaging (MRI)
* Has received prior treatment with 1 or 2 androgen receptor pathway inhibitors (ARPIs) and progressed during or after at least 8 weeks of treatment
* Has provided tumor tissue from a core or excisional biopsy from soft tissue not previously irradiated and obtained after disease progression on the most recent prior therapy
* Has recovered from adverse events (AEs) due to previous anticancer therapies
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Is unable to swallow tablets/capsules
* Has any of the following indicators of interstitial lung disease (ILD)/pneumonitis:
• Has any history of ILD/pneumonitis that required steroid use, except for a history of radiation pneumonitis that did not require steroids
• Has current ILD/pneumonitis
• Has a clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
* Has uncontrolled or significant cardiovascular disease
* Has received prior treatment with a taxane-based chemotherapy agent for metastatic castration-resistant prostate cancer (mCRPC)
* Has had prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities
* Has a "superscan" bone scan
UTSW NORC Pilot Spinal Cord Injury Dietary Program
The goal of this observational study is to learn about the effects of a 9-week dietician-guided program modified from the National Diabetic Prevention Program (modified DPP-diet) in people with spinal cord injury on body composition and insulin sensitivity.
The main question it aims to answer is:
Does 9 week modified DPP-diet reduce body fat percentage and insulin resistance?
Participants will:
Have 9 weeks of Telehealth visit with dietician certified in providing DPP. Visit the laboratory before, immediately and 9 weeks after completion of the modified DPP-diet.
Share with the researcher on the perceived benefit and obstacles in implementing the modified DPP-diet as part of their daily activities.
* age 18-65 years old
* have had SCI for more than one year
* not independently ambulatory
* primarily uses a wheelchair for mobility
* community-dwelling
* without comorbidities listed in the exclusion criteria
Exclusion Criteria:
* uncontrolled type 2 diabetes mellitus
* pregnancy
* active systemic disease, e.g., heart disease, real failure/insufficiency, multiple myeloma, lupus with nephropathy, sickle cell disease, symptomatic myasthenia gravis, poorly controlled hypo- or hyperthyroidism.
OTHER: Telehealth with dietician
Obesity and Obesity-related Medical Conditions, Spinal Cord Injury, Chronic
Testing the Addition of an Anti-Cancer Drug, Cabozantinib to the Immunotherapy Drug Cemiplimab (REGN2810), in Adolescents and Adults With Advanced Adrenocortical Cancer
This phase II trial compares the effect of giving cabozantinib with or without cemiplimab in patients with adrenocortical cancer that has spread to nearby tissue or lymph nodes (locally advanced), and that cannot be removed by surgery (unresectable) or that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Cabozantinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib with cemiplimab may kill more tumor cells in patients with locally advanced unresectable or recurrent/metastatic adrenocortical cancer.
* STEP 1: Patients must have documented histologically or cytologically confirmed adrenocortical carcinoma
* STEP 1: Locally advanced unresectable or recurrent/metastatic disease
* STEP 1: Evaluable disease as defined by RECIST v 1.1
* STEP 1: Up to 3 prior lines of systemic therapy will be allowed in the unresectable/recurrent/metastatic setting. Treatment naïve patients will be allowed.
* Note: Combination etoposide, doxorubicin, cisplatin, and mitotane (EDP-M) is considered 1 line of therapy. For patients who received mitotane ≤ 6 months prior to registration, mitotane should be discontinued 28 days prior to study registration AND a mitotane level must be documented to be \< 2 mg/L prior to registration. Patients who have received mitotane within 6 months of enrollment and who have mitotane levels ≥ 2 mg/L will not be eligible to enroll
* STEP 1: No prior treatment with cabozantinib or other cMET inhibitors, or anti-CTLA-4, or anti-PD-1/PD-L1 therapy
* STEP 1: Prior external beam radiation therapy (any area radiated within a month prior to study registration cannot be used as an index lesion and only growth outside of the radiation field can be considered for disease progression), systemic cytotoxic chemotherapy, targeted therapies will be allowed, as long as not administered within 14 days before study registration, and provided any acute treatment-related associated toxicities have recovered to ≤ grade 1 except for alopecia, peripheral neuropathy or other residual toxicities that are not deemed clinically significant
* STEP 1: Potential trial participants should have recovered from clinically significant adverse events, and wound healing is clinically adequate of their most recent therapy/intervention prior to enrollment
* STEP 1: Age 12 years and above; and BSA ≥ 1.2m\^2
* STEP 1:
* Eastern Cooperative Oncology Group (ECOG) performance 0 - 2 (age 18 and above); or
* Patients 12 to \<16 years of age will be assessed by the Lansky scale and should have a score ≥ 50; or
* Patients ≥ 16 to \<18 years of age will be assessed by the Karnofsky scale, and should have a score ≥ 50
* STEP 1: Absolute neutrophil count (ANC) ≥ 1,000/mcL without colony stimulating factor support within 2 weeks prior
* Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory
* STEP 1: Platelet count ≥ 100,000/mcL
* Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory
* STEP 1: Hemoglobin ≥ 8 g/dL
* Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory
* STEP 1: Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* For patients with known Gilbert's disease, bilirubin ≤ 3 mg/dL
* STEP 1: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x upper limit of normal (ULN)
* STEP 1: Random Urine Creatinine Ratio (UPCR) ≤ 1 mg/mg
* STEP 1: Calculated (Calc.) creatinine clearance ≥ 30 mL/min
* STEP 1: Mitotane level \< 2 mg/L\*
* Only applicable for patients who have received mitotane ≤ 6 months prior to registration
* STEP 1: Must have assessment of adrenal steroid production within 3 months prior to registration as patients will be stratified based on corticosteroid production
* Patients will be classified as corticosteroid producing if random plasma adrenocorticotropic hormone (ACTH) is \< 20 pg/mL plus random serum cortisol is \> 20 mcg/dL in the absence of anti-cortisol therapy. Patients already on anti-cortisol therapy will be classified as having corticosteroid producing tumors regardless of their plasma ACTH and serum cortisol levels, as these levels can be affected by anti-cortisol therapy
* STEP 1: Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects based on animal reproduction studies. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test, per institution standard, done ≤ 14 days prior to registration is required
* STEP 1: 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 within 28 days of registration. To be eligible for this trial, patients should be class II or better
* STEP 1: No known history of congenital long QT syndrome
* STEP 1: No known history of myocarditis
* STEP 1: No myocardial infarction (MI) or unstable angina within 6 months of registration
* STEP 1: No clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding within 6 months of registration including, but not limited to: active peptic ulcer, known endoluminal metastatic lesion(s) with history of bleeding, inflammatory bowel disease, or other gastrointestinal conditions with increased risk of perforation
* STEP 1: No history of gastrointestinal (GI) perforation within 6 months of registration
* STEP 1: No known tumor with invasion into the GI tract from the outside causing increased risk of perforation or bleeding within 28 days of registration
* STEP 1: No current radiologic or clinical evidence of pancreatitis
* STEP 1: No history of clinically significant non-healing wounds or ulcers within 28 days of registration
* STEP 1: No uncontrolled hypertension within 14 days of registration (defined as sustained systolic blood pressure (SBP) ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg despite optimal medical management)
* STEP 1: No known endobronchial lesions involving the main or lobar bronchi and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage. (CT with contrast is recommended to evaluate such lesions.). No hemoptysis greater than ½ teaspoon (2.5 mL) or any other signs of pulmonary hemorrhage within the 3 months prior to registration
* STEP 1: No history of pneumonitis
* STEP 1: No known tumor invading or encasing any major blood vessels
* STEP 1: No history of fracture within 28 days of registration
* STEP 1: No known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks after major surgery (e.g., removal or biopsy of brain metastasis) before registration. Eligible patients must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment
* STEP 1: Major surgery (e.g., laparoscopic nephrectomy, GI surgery, within 2 weeks before registration. Minor surgeries within 10 days before registration. Patients with clinically relevant ongoing complications from prior surgery are not eligible
* STEP 1: Verbalizes the ability to swallow oral tablet formulation
* STEP 1: No history of allergic reaction attributed to compounds of similar chemical or biological composition to cabozantinib
* STEP 1: 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 will be eligible
* STEP 1: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
* STEP 1: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* STEP 1: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* STEP 1: No active autoimmune disease: or history of autoimmune disease that might recur, and which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of:
* immune related neurologic disease,
* multiple sclerosis,
* autoimmune (demyelinating) neuropathy,
* Guillain-Barre syndrome (GBS), myasthenia gravis,
* systemic autoimmune disease such as systemic lupus erythematosus (SLE),
* connective tissue diseases,
* scleroderma, inflammatory bowel disease (IBD),
* Crohn's, ulcerative colitis,
* patients with a history of toxic epidermal necrolysis (TEN),
* Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease,
* Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible,
* Patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome, and psoriasis controlled with topical medication and patients with only positive serology, such as antinuclear antibodies (ANA) or anti-thyroid antibodies, should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* STEP 1: No steroid use \> 10 mg prednisone equivalents daily. A brief course of corticosteroids for prophylaxis or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as is steroid pre-medication for contrast allergy
* STEP 1: Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study
* STEP 1: Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
* STEP 1: Herbal supplements and traditional Chinese medicines are not allowed
* STEP 1: Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g., clopidogrel) within 5 days of registration. Allowed use of anticoagulants include: prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH), therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, apixaban. Also use of anticoagulants is allowed in patients with known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
* STEP 2 (CROSSOVER): Patients must have demonstrated radiographic progression of disease on cabozantinib monotherapy (Arm A) per RECIST version 1.1 criteria
* Patients must cross-over to Arm C within 4 weeks (+/- 1 week) after radiographic documented progression and do not need to have a repeat radiographic assessment prior to starting cabozantinib and cemiplimab (REGN2810). The progression CT may serve as eligibility for crossover and as the baseline tumor measurement
* STEP 2 (CROSSOVER): Patients that were discontinued on cabozantinib, or currently meet criteria for discontinuation of cabozantinib due to toxicity are not eligible to cross-over.
* Note: Patients who underwent dose reduction of cabozantinib during treatment on Arm A will not re-escalate dose at or after cross-over to Cabo-Cemiplimab (REGN2810) (Arm B)
* STEP 2 (CROSSOVER): Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done ≤ 14 days prior to re-registration is required
Daily Nitrofurantoin Versus Bladder Fulguration Plus Daily Nitrofurantoin for Women With Recurrent Urinary Tract Infections
The goal of this clinical trial is to learn if the drug Nitrofurantoin (NF) taken as a daily antibiotic, works to treat cystitis compared to electrofulguration (EF) and Nitrofurantoin (NF) daily antibiotic.
* Females 18 to 85 years old with at least a 1-year history of culture documented uncomplicated rUTI.
* Diagnosis of rUTI, defined as ≥ 3 symptomatic UTIs in 12 months or ≥ 2 in 6 months.
* Currently free from a UTI determined based on absence of symptoms as determined by the UTI symptom assessment questionnaire and negative urine culture (\<10\^3 colony forming units per ml of urine).
* A negative upper and lower urinary tract evaluation, including pelvic examination for pelvic organ prolapse (less than or equal to stage 2), measurement of post-void residual (less than 50 ml), and imaging (which may include renal ultrasound and standing voiding cystourethrogram) to exclude kidney stone, hydronephrosis, reflux, or urethral diverticulum.
* Office cystoscopy documenting stages 1 or 2 of chronic cystitis.
* Likely to stay in the geographic region for the duration of the study.
* ASA class II or less.
Exclusion Criteria:
* Patients on antibiotics at baseline (i.e., suppressive therapy or antibiotic therapy for non-urinary infections).
* Patients on self-start therapy (i.e., taking antibiotics upon start of urinary symptoms concerning for UTI).
* Patients on prophylactic antibiotics started in the last 3 months and unwilling to discontinue, or intention to start in the next 12 months.
* Complicated UTIs, including neurogenic bladder condition (i.e., multiple sclerosis, Parkinson's disease, spinal cord injury), bladder augmentation, or urinary diversion.
* Patients with urinary catheters (including indwelling Foley, intermittent catheterization, and suprapubic catheters).
* Uncontrolled diabetes (HbA1c \>9).
* Pregnancy
* Allergy or resistance to Nitrofurantoin.
* Chronic lung or liver condition precluding the use of Nitrofurantoin, including abnormal chest X ray or elevated liver function tests.
* Chronic renal insufficiency (creatinine over 1.5 g/dl or GFR less than 40) precluding the use of Nitrofurantoin.
* History of chronic diarrhea requiring regular therapy.
* Patients with psychosis, dementia, swallowing disorders, or any other ability to take Nitrofurantoin reliably at home.
* BMI over 40.
* Use of Uromune or other vaccine approaches to reduce rUTI episodes
* Participation in a research study involving an investigational product in the past 12 weeks.
* Patients receiving phage therapy.
* Current diagnosis of interstitial cystitis.
* Patients with medical conditions requiring excessively large amounts of fluid intake.
Ketamine add-on Therapy for Established Status Epilepticus Treatment Trial (KESETT) (KESETT)
The goal of this clinical trial is to determine if treatment of patients with two doses of ketamine plus levetiracetam versus levetiracetam alone leads to more effective control of status epilepticus.
Pamela Okada, MD pamela.okada@utsouthwestern.edu
ALL
1 Year to old
PHASE3
This study is NOT accepting healthy volunteers
NCT06907173
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Inclusion Criteria:
* The patient was witnessed to have a convulsive seizure for greater than 5-minute duration
* The patient received an adequate dose of benzodiazepines. The doses may be divided.
* The last dose of a benzodiazepine was administered 5-30 minutes before study drug administration.
* Continued or recurring seizures in the Emergency Department.
* Age 1 years or older
* Known or estimated weight ≥10 Kg
Exclusion Criteria:
* Known pregnancy
* Prisoner
* Opt-out identification or otherwise known to be previously enrolled in KESETT
* Treatment with a second line anticonvulsant (FOS, PHT, VPA, LEV, phenobarbital, or other agents defined in the MoP) for this episode of SE
* Treatment with sedatives with anticonvulsant properties other than benzodiazepines for this episode of SE(propofol, etomidate, ketamine or other agents defined in the MoP)
* Endotracheal intubation prior to enrollment
* Acute traumatic brain injury clearly precedes seizures
* Scalp injury or burn preventing EEG placement
* Known allergy or other known contraindication to KET or LEV
* Hypoglycemia \< 50 mg/dL
* Hyperglycemia \> 400 mg/dL
* Cardiac arrest / post-anoxic seizures
A Clinical Study of Zilovertamab Vedotin (MK-2140) Plus Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Polatuzumab Vedotin Plus R-CHP in People With Diffuse Large B-cell Lymphoma (DLBCL) (MK-2140-011/waveLINE-011)
Researchers are looking for ways to treat germinal center B-cell-like diffuse large B-cell lymphoma (GCB DLBCL). DLBCL is a fast-growing blood cancer that affects B-cells. GCB is a type of DLBCL that affects young B-cells that are still maturing.
The goal of this study is to learn if more people who receive zilovertamab vedotin (MK-2140) and R-CHP have the cancer respond (go away) than those who receive polatuzumab vedotin and R-CHP.
The main inclusion criteria include but are not limited to the following:
* Has histologically confirmed diagnosis of germinal center B-cell (GCB) subtype of diffuse large B-cell lymphoma (DLBCL), by prior biopsy, according to the World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues.
* Has positron emission tomography (PET) positive disease at screening, defined as 4 to 5 on the Lugano 5-point scale.
* Has received no prior treatment for their DLBCL.
* Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART).
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load prior to randomization.
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has a history of transformation of indolent disease to DLBCL.
* Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL) or Grey zone lymphoma.
* Has Ann Arbor Stage I DLBCL.
* Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication.
* Has clinically significant pericardial or pleural effusion.
* Has ongoing Grade \>1 peripheral neuropathy.
* Has a demyelinating form of Charcot-Marie-Tooth disease.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Has ongoing corticosteroid therapy.
* Known additional malignancy that is progressing or has required active treatment within the past 2 years.
* Known active central nervous system (CNS) lymphoma.
* Has active autoimmune disease that has required systemic treatment in the past 2 years.
* Has active infection requiring systemic therapy.
* Has active HBV (defined as HBsAg positive and detectable HBV deoxyribonucleic acid (DNA)) and HCV (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid (RNA)) infection.
* Has history of stem cell/solid organ transplant.
Obesity is a major risk factor for hypertensive disorders of pregnancy (HDP). The underlying mechanisms are largely unclear, but maternal vascular endothelial dysfunction is likely involved. Endothelial dysfunction in HDP could be attributed to 1) alterations in the L-arginine/nitric oxide (NO) pathway, and 2) an increase in endothelin-1 (ET-1). Additionally, augmented sympathetic vasoconstriction may also contribute to HDP. Chronic (repeated) whole-body heat exposure has been shown to increase NO bioavailability, decrease ET-1, and cause functional and structural adaptations in the vasculature. All these can improve vascular function, attenuate sympathetic (re)activity, lower blood pressure (BP), and reduce cardiovascular risk in non-pregnant individuals. Whether this is also true after regional (leg) heating in high-risk pregnant women is unknown. The investigators' central hypothesis is that chronic leg heating will be effective in improving vascular endothelial function and attenuating sympathetic vasoconstriction, leading to a reduction of the risk for HDP in pregnant women with obesity. The overarching goal of this proposal is to determine the vascular and neural effects of chronic leg heating in obese pregnancy. The study team plans to enroll pregnant women with obesity between 12-14 weeks of gestation and randomly assign them to either an intervention group or a control group (1:1 ratio). Participants in the intervention group will perform 16 weeks of home-based leg heating using a portable sauna blanket up to the hip (temperature of the blanket will be set at 65°C, 4 times/week, 45 min/session), whereas women in the control group will set the temperature of the blanket at 35°C at the same frequency and duration. Participants will be evaluated at baseline and then at 28-30 weeks of gestation. Aim 1 will determine the effects of chronic leg heating on maternal vascular function and surrogate markers of HDP. Aim 2 will determine the effects of chronic leg heating on sympathetic vasoconstriction and BP. Findings from this project will provide insight on the extent and potential mechanisms of how chronic leg heating works for improving vascular endothelial function and sympathetic vasoconstriction in pregnant women with obesity. Results obtained will set a foundation for future large multicenter clinical trials to determine the efficacy and generalizability of home-based leg heat therapy as a safe, ease-of-use, cost-effective, and non-drug approach for reducing the risk of HDP.
* Women with overweight or obesity (self-reported pre-pregnancy body mass index ≥25 kg/m2) between 10-14 weeks of gestation and aged 18-45 years old will be enrolled.
* Both normotensive and hypertensive (office sitting systolic BP 140-150 mmHg and/or diastolic BP 90-100 mmHg) pregnant women will be enrolled if they are not on any antihypertensive drug treatment.
* We will enroll both nulliparous and multiparous women.
* There is no restriction regarding race/ethnicity and socioeconomic status.
* Women with a history of HDP will be allowed to participate.
* Women taking low-dose aspirin will be allowed to participate and aspirin use will be documented.
Exclusion Criteria:
* Current multiple pregnancies (e.g., twins, triplets, etc.).
* Known major fetal chromosomal or anatomical abnormalities diagnosed during the study.
* Recurrent miscarriage (three or more, to avoid antiphospholipid antibody syndrome).
* Office sitting BP \<100/55 mmHg or \>150/100 mmHg (for safety reasons).
* Evidence of cardiovascular, pulmonary, or neurological diseases.
* Diabetes mellitus (to avoid its effects on vascular endothelial function and sympathetic vasoconstriction).
* Kidney disease (serum creatinine \>0.9 mg/dL).
* Clinical known deep vein thrombosis, clinical symptoms and history of deep vein thrombosis, or dermatological lesions.
* History of drug or alcohol abuse within the last 2 years.
* Current tobacco use.
* Pregnant women who do not have air conditioning at home during summer (for safety reasons).