Clinical Trials Commons^™

Cabozantinib Plus Atezolizumab In Previously Untreated Advanced Hepatocellular Carcinoma And Previously Treated Gastric Cancer And Gastroesophageal Junction Adenocarcinoma: Results From Two Expansion Cohorts Of A Multicentre, Open-Label, Phase 1b Trial (Cosmic-021)., Daneng Li, Yohann Loriot, Adam Burgoyne, James Cleary, Armando Santoro, Daniel Lin, Santiago Ponce Aix, Ignacio Garrido-Laguna, Ramu Sudhagoni, Xiang Guo, Svetlana Andrianova, Scott Paulson

Kimmel Cancer Center Faculty Papers

BACKGROUND: Cabozantinib is approved for previously treated advanced hepatocellular carcinoma (aHCC) and has been investigated in gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJ). Atezolizumab plus bevacizumab is approved for unresectable or metastatic HCC untreated with prior systemic therapy. We evaluated efficacy and safety of cabozantinib plus atezolizumab in aHCC previously untreated with systemic anticancer therapy or previously treated GC/GEJ.

METHODS: COSMIC-021 (ClinicalTrials.gov, NCT03170960) is an open-label, phase 1b study in solid tumours with a dose-escalation stage followed by tumour-specific expansion cohorts, including aHCC (cohort 14) and GC/GEJ (cohort 15). Eligible patients were aged ≥18 years with measurable locally advanced, …

Prt543, A Protein Arginine Methyltransferase 5 Inhibitor, In Patients With Advanced Adenoid Cystic Carcinoma: An Open-Label, Phase I Dose-Expansion Study, Renata Ferrarotto, Paul Swiecicki, Dan Zandberg, Robert Baiocchi, Robert Wesolowski, Cristina Rodriguez, Meredith Mckean, Hyunseok Kang, Varun Monga, Rajneesh Nath, Neil Palmisiano, Naveen Babbar, William Sun, Glenn Hanna

Department of Medical Oncology Faculty Papers

OBJECTIVES: Currently, no systemic treatments are approved for patients with recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC). PRT543, a protein arginine methyltransferase 5 inhibitor that downregulates NOTCH1 and MYB signalling in tumours, is a potential candidate for R/M ACC treatment. We report the safety, tolerability and preliminary efficacy of PRT543 in a dose-expansion cohort of patients with R/M ACC.

MATERIALS AND METHODS: This phase I multicentre, open-label, sequential-cohort, dose-escalation and dose-expansion study (NCT03886831) enrolled patients with advanced solid tumours and select haematologic malignancies. Dose-escalation study design and results were reported previously. In the dose expansion, patients with R/M ACC …

Stereotactic Mr-Guided On-Table Adaptive Radiation Therapy (Smart) For Borderline Resectable And Locally Advanced Pancreatic Cancer: A Multi-Center, Open-Label Phase 2 Study, Michael Chuong, Percy Lee, Daniel Low, Joshua Kim, Kathryn Mittauer, Michael Bassetti, Carri Glide-Hurst, Ann Raldow, Yingli Yang, Lorraine Portelance, Kyle Padgett, Bassem Zaki, Rongxiao Zhang, Hyun Kim, Lauren Henke, Alex Price, Joseph Mancias, Christopher Williams, John Ng, Ryan Pennell, M Raphael Pfeffer, Daphne Levin, Adam Mueller, Karen Mooney, Patrick Kelly, Amish Shah, Luca Boldrini, Lorenzo Placidi, Martin Fuss, Parag Jitendra Parikh

Department of Radiation Oncology Faculty Papers

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity.

MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 …

Test Event Example 12/14/23, Metzalli Demolastname

Annual Research Symposium

No abstract provided.

The Dose-Response Effect Of Aerobic Exercise On Inflammation In Colon Cancer Survivors, Justin C. Brown, Stephanie L.E. Compton, Jeffrey A. Meyerhardt, Guillaume Spielmann, Shengping Yang

School of Medicine Faculty Publications

Background; Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. Methods; In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1;1;1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor …

Causal Inference For The Effect Of Continuous Treatment On Time-To-Event Outcomes And Mediation Analysis On Health Disparities In Observational Studies., Triparna Poddar

Electronic Theses and Dissertations

The dissertation comprises two projects related to causal inference based on observational data. In healthcare research, where abundant observational data such as claims data and electronic records are available, researchers often aim to study the treatment effect and the pathway of that effect. However, estimating treatment effects in observational data presents challenges due to confounding factors. The first project focuses on estimating continuous treatment effects for survival outcomes, while the second concentrates on mediation analysis, allowing the exploration of the pathway of the causal effect. Both projects involve addressing confounding variables. In the first project, I investigate estimation of the …

Addressing The Analytical And Computational Challenges Using Machine Learning In Biomedical Research, Yizhuo Wang

Dissertations and Theses (Open Access)

In the contemporary healthcare field, professionals are confronted with an ever-growing volume of clinical data stored in electronic health records, alongside the genomic data stemming from laboratory experiments. As a response to this deluge of data, the application of machine learning (ML) techniques is gaining popularity since ML techniques have demonstrated an exceptional proficiency in processing big data and deciphering complex nonlinear patterns that are intrinsic to biomedical research.

My research leverages ML's capabilities to address the computational challenges spanning diverse areas, including adaptive clinical trial designs, survival analysis, and high-dimensional genetic data analysis. Specifically, Chapter 2 focused on the …

Repurposing The Fda-Approved Anthelmintic Pyrvinium Pamoate For Pancreatic Cancer Treatment: Study Protocol For A Phase I Clinical Trial In Early-Stage Pancreatic Ductal Adenocarcinoma, Francesca M. Ponzini, Christopher W. Schultz, Benjamin E. Leiby, Shawnna Cannaday, T. Yeo, James Posey, Wilbur B. Bowne, Charles Yeo, Jonathan R. Brody, Harish Lavu, Avinoam Nevler

Department of Surgery Faculty Papers

BACKGROUND: Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we report about an ongoing phase I open-label, single-arm, dose escalation clinical trial to determine the safety and tolerability of PP in PDAC surgical candidates.

METHODS AND ANALYSIS: In a 3+3 dose design, PP is initiated 3 days prior to surgery. The first three patients will be treated with the initial dose of PP at 5 mg/kg orally for 3 days prior to surgery. Dose doubling will …

Sickle Cell Disease Treatment With Arginine Therapy (Start): Study Protocol For A Phase 3 Randomized Controlled Trial., Chris A Rees, David C. Brousseau, Daniel M Cohen, Anthony Villella, Carlton Dampier, Kathleen Brown, Andrew Campbell, Corrie E Chumpitazi, Gladstone Airewele, Todd Chang, Christopher Denton, Angela Ellison, Alexis Thompson, Fahd Ahmad, Nitya Bakshi, Keli D Coleman, Sara Leibovich, Deborah Leake, Dunia Hatabah, Hagar Wilkinson, Michelle Robinson, T Charles Casper, Elliott Vichinsky, Claudia R Morris

Department of Pediatrics Faculty Papers

BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.

METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 …

The Importance Of Contrast Sensitivity, Color Vision, And Electrophysiological Testing In Clinical And Occupational Settings, Frances Silva

Theses & Dissertations

Visual acuity (VA) is universally accepted as the gold standard metric for ocular vision and function. Contrast sensitivity (CS), color vision, and electrophysiological testing for clinical and occupational settings are warranted despite being deemed ancillary and minimally utilized by clinicians. These assessments provide essential information to subjectively and objectively quantify and obtain optimal functional vision. They are useful for baseline data and monitoring hereditary and progressive ocular conditions and cognitive function. The studies in this dissertation highlight the value of contrast sensitivity, color vision, and cone specific electrophysiological testing, as well as the novel metrics obtained with potential practical clinical …

Predicting Hiv Vaccine-Mediated Protection Level To Identify Immune Correlates Using Positive Unlabeled Learning, Shiwei Xu

Dartmouth College Ph.D Dissertations

The development of a vaccine for Human Immunodeficiency Virus type 1 (HIV-1) is a crucial step in preventing the global spread of AIDS. To ensure the progress and effectiveness of this vaccine, it is essential to establish efficient biotechnology platforms and data mining methods. These methods would help identify immune characteristics that distinguish individuals with varying levels of vaccine-induced protection and determine the underlying factors that contribute to protection against HIV acquisition. While previous studies have focused on identifying immune markers associated with infection outcomes among vaccinated patients, it is important to acknowledge the limitations of traditional case-control analytical protocols …

Do Firms Respond To Peer Disclosures? Evidence From Disclosures Of Clinical Trial Results, Vedran Capkun, Yun Lou, Clemens A. Otto, Yin Wang

Research Collection School Of Accountancy

Using data on the registration of clinical trials and the disclosure of trial results, we examine how firms respond to peer disclosures. We find that firms are less likely to disclose their own trial results if the results of a larger number of closely related trials are disclosed by their peers. This relation is stronger if the firms face higher competition (as measured by the number of competing trials). It is weaker if the firms are further along in their research than the peers (as measured by the trials’ phase) and if the peers’ disclosures convey more negative news (as …

Bayesian Semi-Mechanistic Dose-Finding Designs For Phase I Oncology Trials, Chao Yang

Dissertations and Theses (Open Access)

Bayesian adaptive designs are getting more popular in research and in practice because they are flexible and efficient in evaluating an experimental drug. In oncology, despite the great advances in novel dose-finding designs, the high failure rates of clinical cancer drug development from phase I to III trials call for further improvements on novel designs, in addition to the need to promote and adopt novel designs in practice. Because anticancer agents often have a narrow therapeutic index, an accurate identification of the maximum tolerated dose (MTD) in a phase I trial is crucial for identifying a tolerable and efficacious dose …

Intellectual Disability Related To De Novo Germline Loss Of The Distal End Of The P-Arm Of Chromosome 17: A Case Report, Eden Pope, Matthew Huertas, Amar Paul, Braden Cunningham, Matthew Jennings, Ryan Perry, Stephanie Chavez, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Hypothesis/Purpose: In this report we present a case of a 20-year-old female with congenital intellectual disability, stunted growth, and hypothyroidism. Competitive genetic hybridization (CHG) revealed a loss of 17p13.3, and the deletion was not present in either parent. This deletion has not previously been characterized, but mutations on the p-arm of chromosome 17 are responsible for Miller-Dieker Syndrome and Isolated Lissencephaly Sequence, both of which share symptoms in common with the patient.

Methods: Peripheral mononuclear cells (PBMCs) were used for karyotyping and competitive genetic hybridization (CHG). Bioinformatic analysis was carried out using the Genome Data Viewer (ncbi.nlm.nih.gov/genome/gdv).

Results: Karyotype was …

Investigating Respiratory Simplification Caused By Prenatal Rage Upregulation, Paul Reynolds

Annual Research Symposium

No abstract provided.

Potential Role For Rage In The Development Of Secondhand Smoke-Induced Chronic Sinusitis, Paul Reynolds

Annual Research Symposium

No abstract provided.

Rage Inhibition Reduces Timp And Decreases Cell Invasion In Cigarette Smoke Extract (Cse) Treated Oral Squamous Carcinoma Cells, Paul Reynolds

Annual Research Symposium

No abstract provided.

Inflammatory Cytokine Elaboration Following Secondhand Smoke Exposure Is Mediated In Part By Rage Signaling, Paul Reynolds

Annual Research Symposium

No abstract provided.

Rage Availability Lessens The Degree Of Dysfunctional Mitochondrial Bioenergetics Following Chronic Secondhand Smoke Exposure, Paul Reynolds

Annual Research Symposium

No abstract provided.

Gestational Dependent Responses To Second Hand Smoke (Shs) In Mouse Pregnancies, Paul Reynolds

Annual Research Symposium

No abstract provided.

Reversible Emerging Neuropsychological Pattern In Chronic Intractable Migraine, Tanner Williford, Pooja Chemiti, Mason Allen, Brandon Burrell, Stephanie Chavez, Jude Emego, Bridger Gunter, Matthew Huertas, Matthew Jennings, Roshni Jogin, Paulo Kelly, Laura Minor, Steven Salazar, Jameson Williams, David W. Sant, John A. Kriak, Kyle B. Bills

Annual Research Symposium

No abstract provided.

The Science Of Oral Carbapenems, Landon Olsen, Daniel J. Yang, Aiyi Chen, Thahn-Liem Vu, H. Stephen Lee

Annual Research Symposium

No abstract provided.

The Immunomodulating Effects Of Morphine Dependence And Withdrawal In Rat Lung, Liver, Spleen And Blood, Yensi Munoz

Annual Research Symposium

No abstract provided.

The Current State Of Underrepresented Osteopathic Minorities In Competitive Specialties, Emmanuel Oyalabu, Steve Guzman, Dashon Eure, Ezenna Obilor

Annual Research Symposium

It is well documented that barriers exist for underrepresented minorities to enter the field of medicine and even more competitive residencies. As defined by the NRMP, competitive specialties include but are not limited to Interventional Radiology, Orthopedic Surgery, Plastic Surgery, Radiation Oncology, Vascular Surgery, Neurosurgery, Dermatology, and Otornylogy (NRMP-AMA). A large number of osteopathic medical school graduates have a history of going into primary care specialties because many osteopathic medical schools have a primary care focus (Primary Care- Osteopathic Medicine). The emphasis on primary care, whether intentional or not, can foster a less-than-advantageous environment for underrepresented minority students (URM), pursuing …

Appearance Of Two Distinct Clusters Of Glucose Dysregulation In Chronic Intractable Migraine, Roshni Jogin, Kaitlyn Mcfarland, Aparna Naik, Tanner Williford, Matthew Conway, Amar Paul, John A. Kriak, David W. Sant, Kyle B. Bills

Annual Research Symposium

No abstract provided.

Heterodyned Whole-Body Vibration Ameliorates Anxiety In Opioid-Use Disorder, Kailee Edwards, Braden Cunningham, Alfred Amendolara, Marryam Anwar, Jon Gonzales, Roshni Jogin, Wyatt Magoffin, Amar Paul, Ryan Perry, James Pike, Nathan Swallow, Steven Tung, Mary Seamons, Andrew Payne, John A. Kriak, David W. Sant, David W. Sant

Annual Research Symposium

No abstract provided.

Planning A Review Of The Pathogenesis And Management Of Valley Fever, Seattle Shakur

Annual Research Symposium

No abstract provided.

Clinical Trial Subject Recruitment: Research Immersion Experience, Brooklyn Janes

Annual Research Symposium

No abstract provided.

Serdexmethylphenidate/Dexmethylphenidate – A Promising Treatment Option For Childhood Attention Deficit Hyperactivity Disorder (Adhd), N Troy To, H Stephen Lee

Annual Research Symposium

To review the phase 2 and phase 3 clinical trials of Serdexmethylphenidate and dexmethylphenidate (SDX/d-MPH) in the treatment of Attention Deficit/Hyperactivity disorder (ADHD) in children.

Mclena-1: A Phase Ii Clinical Trial For The Assessment Of Safety, Tolerability, And Efficacy Of Lenalidomide In Patients With Mild Cognitive Impairment Due To Alzheimer's Disease; Trial Design And Rationale, Boris Decourt

Annual Research Symposium

No abstract provided.