Merrill, Wisconsin

Testing Two Interventions to Improve Health Outcomes and Quality of Life Among Rural Older Adults Living With HIV

A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma

This multicenter, randomized, double-blind, placebo-controlled Phase 3 study is designed to compare the efficacy and safety of two dose levels of ficlatuzumab combined with cetuximab (Arm 1 or Arm 2) to a control arm of placebo plus cetuximab (Arm 3) in participants with R/M human papilloma virus (HPV)-negative HNSCC. Eligible participants must have failed prior therapy with an anti-PD-1 [programmed cell death protein 1] or PD-L1 [programmed death ligand 1] immune checkpoint inhibitor (ICI) and with platinum-based chemotherapy, administered in combination or sequentially. Failure of prior treatment may be due to progression of disease or intolerance to treatment. It is anticipated that the study will enroll approximately 410 participants across 3 arms.

Study of Tinengotinib VS. Physician's Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma

Approximately 200 subjects will be enrolled. Eligible subjects will be randomized in a 2:2:1 ratio to receive tinengotinib 8 mg QD, tinengotinib 10 mg QD or Physician's Choice in Part A; and eligible subjects will be randomized in a 2:1 ratio to receive the recommended Part B dose or selected dose or Physician's Choice in Part B.

Assessment of Optune Therapy for Patients with Newly Diagnosed Glioblastoma Using Advanced MRI

Protocol Summary: Optune therapy is a newly approved treatment for patients with glioblastoma. This therapy demonstrated comparable outcomes for patients with recurrent GBM, in comparison to standard therapies, but better quality of life. More recently, in an interim analysis of 315 patients with GBM, adding Tumor Treating Fields (TTFields) to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival. It also has demonstrated promise in other cancers such as pancreas, mesothelioma, ovarian and lung. However, in order to optimize the treatment regimen, and potentially predict which patients are most likely to respond, reliable ways of evaluation are necessary. Advanced perfusion and diffusion MRI methods have shown utility with other treatments such as bevacizumab. Preliminary data suggests the same might be true for the evaluation of Optune therapy. The team therefore proposes to determine the utility of these methods to predict response to Optune therapy. A successful result will have wide-ranging implications not only for the optimization of Optune treatment of brain cancer but also other cancers shown to benefit from this novel therapy. Objective: To compare standard and advanced MRI for their ability to predict response to Optune therapy. The team's approach will be to obtain both standard and advanced MRI in patients with newly diagnosed glioblastoma undergoing adjuvant chemotherapy plus Optune therapy. The ability of standard and advanced MRI to predict response will be assessed. The hypothesis is that perfusion and/or diffusion imaging metrics can be used to predict response to and elucidate mechanisms of action for Optune treatment.

Telehealth as a Modality to Increase the Uptake of PrEP Services in Black and Latino: "e-PrEP"

The goal of this study is to determine whether incorporating a telehealth model that allows for same-day appointments for PrEP delivery with the support of navigation leads to increased uptake and persistence of PrEP in young MSM/transgender of color and individuals in rural communities that have disproportionately not used PrEP. The investigators will accomplish this by using an effectiveness-hybrid design that will allow us to both evaluate the interventions impact on relevant clinical outcomes as well as the effectiveness of the implementation strategy. Our hypothesis is that by removing some of the barriers to care such as transportation, childcare, work schedule and potentially stigma with repeated clinic visits, the investigators will increase the uptake and persistence of PrEP amongst communities who historically have had many barriers to care and have not started PrEP.

Safety and Effectiveness of the PXL Platinum 330 System With Riboflavin Solution for Refractory Corneal Ulcers

This is a prospective, 2-arm parallel-group, single-blind, randomized multicenter study to determine the safety and effectiveness of the PXL Platinum 330 System for performing CXL in eyes with refractory corneal ulcers. Subjects with a history of non-resolving infective corneal ulcers will be evaluated initially for suitability as a candidate for CXL. Subjects who are candidates for CXL will be asked to participate in this study and will undergo the required screening procedures to determine study eligibility. Informed consent will be obtained from each subject before performance of any required study procedures that are not part of the investigator's routine examination. After completing screening procedures, the diagnosis for each eligible eye will be confirmed. Subjects will be randomized to 1 of 2 groups: 1. Group 1: Standard-of-care therapy (anti fungal drops if there is clinical suspicion for fungus, fortified antibiotics if corneal culture is positive for a specific organism sensitive to a fortified antibiotic, and empiric antibiotic drops based on community prevalence if corneal culture is negative and there is no clinical suspicion for fungus) 2. Group 2: Standard-of-care therapy + CXL Eyes undergoing CXL will have topical anesthetic administered and then have topical riboflavin instilled onto the cornea every 2 min (or longer as needed to assure adequate corneal penetration), after which the cornea will be exposed to UV-A pulsed light 18 mW/cm2 for 10 min. Riboflavin instillation will continue every 2 min during CXL. The CXL procedures will be performed on an outpatient basis using the PXL Platinum 330 System (UV-A light source and riboflavin solution). All use of the PXL Platinum 330 System will be in accordance with this protocol and the general instructions provided by the manufacturer (PESCHKE) in the PXL Platinum 330 Illumination System Operator's Manual. All subjects will be evaluated at Screening/Baseline, Day 0 (Randomization/Treatment), Day 1, Day 3 ( +/- 1 day), Week 1 ( +/- 2 days), Week 2 ( +/- 2 days), Week 4 ( +/- 3 days), and Week 6 ( +/- 4 days) after treatment. Efficacy monitoring throughout the study will include observations at appropriate times for re-epithelialization, size of infection, and corneal culture results. Safety monitoring throughout the study will include observations at appropriate times for pain, IOP, BSCVA, corneal scar size, AEs, clinically significant findings on ophthalmic examination, dilated fundus examination, and slit lamp examination. After treatment, subjects will be followed at the treating physician's discretion.

Safety and Effectiveness of the PXL Platinum 330 System With Riboflavin Solution for Previously Untreated Corneal Ulcers

This is a prospective, 2-arm parallel-group, single-masked, randomized multicenter study to determine the safety and effectiveness of the PXL Platinum 330 System for performing CXL in eyes with previously untreated corneal ulcers. Subjects with documented infectious corneal ulcers that have not been treated (treatment na ve) will be evaluated initially for suitability as candidates for CXL. Subjects who are candidates for CXL will be asked to participate in this study and will undergo the required screening procedures to determine study eligibility. Informed consent will be obtained from each subject before performance of any required study procedures that are not part of the investigator's routine examination. After completing screening procedures, the diagnosis for each eligible eye will be confirmed. Subjects will be randomized to 1 of 2 groups, both including standard of care (SOC) treatment: 1. SOC: Moxifloxacin 0.5% eyedrop therapy every 1 hour (q1h) while awake; to be tapered at treating physician's discretion 2. CXL + SOC: Moxifloxacin 0.5% eyedrop therapy + CXL Eyes undergoing CXL will have topical anesthetic administered and then have topical riboflavin instilled onto the cornea every 2 min (or longer as needed to assure adequate corneal penetration), after which the cornea will be exposed to UV-A pulsed light 18 mW/cm2 for 10 min. Riboflavin instillation will continue every 2 min during CXL. The CXL procedures will be performed on an outpatient basis using the PXL Platinum 330 System (UV-A light source and riboflavin solution). All use of the PXL Platinum 330 System will be in accordance with this protocol and the general instructions provided by the manufacturer (PESCHKE) in the PXL Platinum 330 Illumination System Operator's Manual. All subjects will be evaluated at Screening/Baseline, Day 0 (Randomization/Treatment), Day 1, Day 3 ( 1 day), Week 1 ( 2 days), Week 2 ( 2 days), and Week 4 ( 3 days) after treatment. Efficacy monitoring throughout the study will include observations at appropriate times for re-epithelialization, size of infection, and corneal culture results. Safety monitoring throughout the study will include observations at appropriate times for pain, IOP, BSCVA, corneal scar size, AEs, clinically significant findings on ophthalmic examination, dilated fundus examination, and slit lamp examination. After treatment, subjects will be followed at the treating physician's discretion.

Mental Imagery to Improve Quadriceps Strength Post Anterior Cruciate Ligament Reconstruction: a Feasibility Study

Computer-guided Action Planning to Support Physical Activity (CAPPA) for Employees with Chronic Knee Symptoms

Chronic knee symptoms (CKS) are associated with pain, loss of independence, and increased mortality. Rates of CKS are increasing, fueled by an aging, obese, and sedentary society. Because CKS first presents in working age adults, it is a major cause of work disability and work productivity loss. Being physically active improves the health of adults who have ongoing (chronic) complaints of knee pain, knee stiffness, or challenges with moving around. Physical activity helps decrease pain, improve stiffness, and improve physical function as it relates to the knee. It also helps people improve their general health. Unfortunately, it is hard for many people to become more physically active. Physical activity can be inconvenient and uncomfortable for many people, and people who join physical activity programs often drop out of them after a short time (3-6 months). However, people are more likely to reach their physical activity goals if they work with a health coach who supports the process. Health coaching often includes a combination of self-monitoring such as using smart devices to monitor outcomes plus the support of goal-directed behavior. Previous research has found that Fitbit tracking can improve behavior for some people who have CKS but not for others. Whereas we know people can receive benefit from coaching, the exact amount of coaching needed remains unknown. Discussion with employee stakeholders have informed our intervention desire as they have asked for a low resource form of coaching available through the workplace. The potential exists to support employees with CKS using an acceptable, low-resource coaching strategy. The goal of this program is to test a brief, scalable PA coaching intervention that can assist employees with CKS attain and maintain healthy PA behavior in worksites in the Midwest. CAPPA is a 12-week pilot randomized controlled trial that will 1) use computer-guided action-planning behavioral intervention to support employees in making physical activity action plans for their health, 2) use data transmitted from a personal fitness tracker (Fitbit) to support coach and employee knowledge about PA performance, and 3) Inform on optimal step up times for participants who do not substantially increase PA. The CAPPA system will put PA feedback in a Movement Dashboard to support study participants. The CAPPA intervention will primarily use video chat to attain and sustain healthy PA behavior across worksites at Advocate Aurora Health. Follow-up measures of PA, pain and physical function are planned at treatment completion and three months following study completion. Specific aims are to: 1) Estimate the efficacy of the intervention to increase objectively measured physical activity, 2) Examine the feasibility, acceptability and sustainability of the CAPPA intervention for the respective workplaces, and 3) Inform the initial step up time for future stepped interventions among participants not substantially increasing their physical activity. This study leverages the combined clinical and technologic expertise of the members of the Physical Activity in Rheumatology Research group at Northwestern University, Northwestern's Arthritis Center Accelerometer unit, Marquette University's Behavior, Engagement and Technology Assessment Lab and Ubiquitous Computing Lab, and Advocate Aurora Health. This research could have a tremendous impact on improving symptoms and quality of life for those with CKS and early KOA. If treatments are successful at Advocate Aurora Health they may be employed in the services they provide to other organizations.

An Observational Research Study to Uncover Subtypes of Cancer Cachexia

PRIMARY OBJECTIVE: I. To identify multiple distinct diagnostic subtypes within the syndrome of CC as defined by host characteristics (e.g. cachexia symptoms, physical activity, physical function, blood biomarkers including hemoglobin and albumin, and body composition) at baseline and change in these factors over time in patients with cancer at high risk for CC. SECONDARY OBJECTIVES: I. To determine the association of each CC phenotype with overall survival. II. To validate CC diagnostic phenotypes developed in a separate, independent cachexia observational study performed by our collaborators at Kaiser Permanente. III. To collect human samples of blood, tumor tissue, and medical images and build a large, comprehensive CC database clinically annotated with cancer-related outcomes, cachexia symptoms, and physical function data. EXPLORATORY OBJECTIVE: I. To evaluate for tumor-derived factors contributing to CC by determining the association between interleukin-6 (IL-6) expression in tumor and IL-6 and CC chemokine ligand 2 (CCL2) levels in the blood in patients with CC. OUTLINE: This is an observational study. Patients complete surveys over 30 minutes, undergo physical function tests over 30 minutes, undergo collection of blood and archived tumor samples, and wear actigraph over 24 hours for 7 days to record daily sleep and exercise activity at baseline and 3-month follow-up. Additionally, patients undergo standard of care positron emission tomography (PET)/computed tomography (CT) scans throughout the study and patients' medical records are also reviewed at baseline, 3-month and 1-year follow-up.