Clinical Research Directory

A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers

Background: Often, metastatic human papillomavirus (HPV) associated cancers cannot be cured. They also do not respond well to treatment. Some forms of colon cancer also have poor responses to treatment. Researchers want to see if a new drug treatment can help people with these types of cancers. Objective: To find a safe dose of entinostat in combination with PDS01ADC and bintrafusp alfa and to see if this treatment will cause tumors to shrink. Eligibility: Adults ages 18 and older who have cervical, oropharyngeal, anal, vulvar, vaginal, penile, squamous cell rectal, or another cancer that may be associated with HPV infection or microsatellite stable small bowel or colorectal cancer. Design: Participants will be screened with a medical history and physical exam. Their ability to do daily activities will be assessed. They may have imaging scans of the brain and/or chest, abdomen, and pelvis. They may have nuclear bone scans. They will have an electrocardiogram to test heart function. They will have blood and urine tests. They may have a tumor biopsy. Participants with skin lesions may have them photographed. Some screening tests will be repeated during the study. Treatment will be done in 28-day cycles. Participants will get bintrafusp alfa through an intravenous catheter every 2 weeks. They will get PDS01ADC as an injection under the skin every 4 weeks. They will take entinostat by mouth once a week. They will complete a medicine diary. Participants will get treatment for 2 years. They will have 1-2 follow-up visits in the 30 days after treatment ends. Then they will be contacted every 6 months to check on their health.

E7 T-cell Receptor (TCR) -T Cell Induction Therapy for Locoregionally Advanced HPV-associated Cancers

The goal of this study is to determine the feasibility of administration of a single dose of E7 TCR-T cells as induction therapy prior to definitive treatment (chemoradiation or surgery) of locoregionally advanced HPV-associated cancers. The intent of E7 TCR-T cell treatment is to shrink or eliminate tumors and thereby facilitate definitive therapy and increase overall survival. This study seeks to determine 1) if E7 TCR-T cells can be administered without undue delay in definitive treatment, 2) the tumor response rate to E7 TCR-T cell treatment, and 3) the disease-free survival rate at 2 and 5 years. Participants will undergo an apheresis procedure to obtain T cells that will be genetically engineered to generate E7 TCR-T cells. They will receive a conditioning regimen, a single infusion of their own E7 TCR-T cells, and adjuvant aldesleukin. Participants will follow up to assess safety and determine tumor response and will return to their primary oncology team for definitive therapy.

KK-LC-1 TCR-T Cell Therapy for Gastric, Breast, Cervical, and Lung Cancer

This is a phase I clinical trial to determine the maximum tolerated dose (MTD) of KK-LC-1 TCR-T cells for the treatment of metastatic cancers that express KK-LC-1. Participants will receive a conditioning regimen, KK-LC-1 TCR-T cells, and aldesleukin. The safety profile and clinical response to treatment will be determined.

Triage of Advanced Cervical Cancer Through Immunotherapy Induction (TRACTION)

To learn if MGD019 can help to control cervical cancer in patients who have yet to receive treatment.

E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers

This is a phase II clinical trial to assess the clinical activity of immunotherapy with E7 TCR-T cells for metastatic HPV-associated cancers. HPV-associated cancers in include cervical, throat, penile, vulvar, vaginal, anal, and other cancers. Participants will receive a conditioning regimen, E7 TCR-T cells, and aldesleukin. Clinical response to treatment will be determined.

A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) as First-line Maintenance Treatment of Cervical Cancer (MK-2870-036/TroFuse-036/GOG-3123/ENGOT-cx22)

Researchers are looking for new ways to treat metastatic cervical cancer. Cervical cancer is cancer in the cervix, the lower part of the uterus (womb). Metastatic means the cancer has spread to other parts of the body. Researchers want to learn about giving the study medicine sacituzumab tirumotecan (also called sac-TMT or MK-2870) along with pembrolizumab and bevacizumab treatments. Sac-TMT is an antibody drug conjugate, which is a type of medicine that attaches to specific targets on cancer cells and delivers treatment to destroy those cells. The goals of this study are to learn: * About the safety of sac-TMT with pembrolizumab and bevacizumab, and if people tolerate them when given together, and * If people who receive sac-TMT and pembrolizumab, with or without bevacizumab, live longer overall or without their cancer getting worse as compared to those who receive standard treatment

A Phase 1/1b of RNDO-564 Single Agent or in Combination With Pembrolizumab in Bladder Cancer and Other Solid Tumors Associated With Nectin-4

The main goal of this study is to evaluate how safe and tolerable RNDO-564 is and to identify the best dose of RNDO-564 as a single agent and in combination with pembrolizumab. The study is focused on participants with certain solid tumors that are in an advanced stage and have certain tumor makers. This will be done by measuring the side effects that participants experience and how severe they are. Additionally, the study will evaluate how RNDO-564 moves into, through, and out of the body and how the treatment affects the body. The second goal of this study is to evaluate how well RNDO-564 works by itself or in combination with pembrolizumab at treating participants' cancer. This will be done by measuring the number of participants who respond to the treatment. The length of time where the tumor does not grow or spread will also be measured. Participants will take RNDO-564 weekly on Days 1, 8 and 15 of a 21 day cycle. Participants in the combination arms will take RNDO-564 as described with pembrolizumab every 3 weeks.

Safety and Tolerability of ²¹²Pb-DOTAM-GRPR1 in Adult Subjects With Recurrent or Metastatic GRPR-expressing Tumors

A Phase 1 Open-Label, First-in-human, Dose Escalation and Expansion Study to Determine the Safety, Tolerability, Dosimetry, Pharmacokinetics, and Preliminary Efficacy of 212Pb-DOTAM-GRPR1 in Adult Participants with Recurrent or Metastatic GRPR-expressing Tumors

PROton Therapy for Post Surgical Treatment of GYNecologic Cancer

This is a single institution, multi-center, Phase II, single-arm study, using Whole Pelvis (WP) Pencil Beam Scanning Proton Radiation (PBS PRT) in the post-surgical, adjuvant setting for definitive treatment of gynecologic cancers. The purpose of this study is to estimate rate of acute clinician-reported gastrointestinal (GI) toxicity using WP PBS PRT in the definitive treatment of gynecologic cancers in the post-surgical, adjuvant setting.

A Study to Evaluate the Safety, Pharmacokinetics, and Activity of Enzelkitug as a Single Agent and in Combination With Checkpoint Inhibitor in Participants With Locally Advanced or Metastatic Solid Tumors

This is a first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of enzelkitug when administered as a single agent and in combination with atezolizumab or pembrolizumab in adult participants with locally advanced or metastatic solid tumors, including non small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), melanoma, triple-negative breast cancer (TNBC), esophageal cancer, gastric cancer, cervical cancer, colorectal cancer (CRC), urothelial carcinoma (UC), clear cell renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Participants will be enrolled in 2 stages: dose escalation and dose expansion.

C-3002: Enhancing Cervical Cancer Screening Access and Follow-up Care at 'CASCADE' Clinical Sites in the United States

The purpose of the CASCADE-3002 project is to improve access to cervical cancer screening among women with Human Immunodeficiency Virus (HIV) receiving care at U.S.-based CASCADE clinical sites. This study will assess the cervical cancer screening cascade and identify multilevel factors that impede access to screening among women with HIV attending Infectious Disease clinics in Georgia and Maryland. In parallel, the study will explore and develop implementation strategies for human papillomavirus (HPV) self-collection to increase screening uptake, adherence, and appropriate clinical follow-up in this population at elevated risk for cervical cancer. Cervical cancer remains a preventable malignancy; however, women with HIV are at substantially increased risk and experience higher rates of cervical cancer compared with women without HIV. The World Health Organization has called for the global elimination of cervical cancer as a public health problem, defined as fewer than 4 incident cases per 100,000 women annually, with targets for vaccination, screening, and treatment coverage. Although the United States has the tools to approach near-elimination, disparities in healthcare access and screening persist, particularly among women with HIV.

Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers

The primary purpose of this study is to assess the safety and tolerability of AB598 in participants with advanced malignancies.

Induction Chemotherapy Plus Cadonilimab for Locally Advanced Cervical Cancer

This is an investigator-initiated, single-arm, phase II clinical study evaluating the efficacy and safety of cadonilimab combined with induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in patients with locally advanced cervical cancer (LACC). Despite standard concurrent chemoradiotherapy, patients with LACC remain at high risk of recurrence and distant metastasis. Cadonilimab, a PD-1/CTLA-4 bispecific antibody, has demonstrated promising antitumor activity in cervical cancer. This study aims to investigate whether induction immunochemotherapy with cadonilimab combined with cisplatin and albumin-bound paclitaxel can improve tumor response before definitive radiotherapy. In addition, the study will explore the association between treatment efficacy and dynamic changes in PD-L1 expression, peripheral blood immune-related biomarkers, and tumor microenvironment immune cell populations during treatment. The primary endpoint is objective response rate (ORR) assessed according to RECIST version 1.1, while secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

Secondary Cervical Cancer Prevention of Vulnerable Women With HPV and HIV Co-infection in India

Cervical cancer (CC) remains one of the most common malignancies among women in India, with nearly 100,000 women diagnosed annually and over 60,000 preventable deaths annually. With high-risk human papillomavirus (HR-HPV) as the causative agent for CC, one risk factor that places women at high risk for CC is human immunodeficiency virus (HIV), as impaired immune response against Human papillomavirus (HPV) may result in persistent HR-HPV infection, a critical risk factor for progression of HPV-related cervical oncogenesis. Progression of precancerous lesions among women living with HIV (WLH) is also associated with: 1) lack of HPV screening; 2) high levels of depressive symptoms and stigma; and 3) malnutrition, which negatively impacts the activation and proliferation of immune cells. Yet programs that offer WLH with comprehensive services focused on HPV screening and psychological and nutritional support are almost non-existent, and the gap is critical. Nutrition plays an integral role in relationship to HPV/HIV co-infection, as demonstrated by an increased risk of HR-HPV associated with poor nutrition; nutritional deficiencies are likewise linked to cervical intra-epithelial neoplasia. The immunological effect of malnutrition may also be exacerbated among WLH due to elevated energy demands of chronic immune activation; worsened with HPV/HIV co-infection. Further, depressive symptoms (aka depression for brevity) partially mediate the effect of food insecurity on HIV viral suppression. In our completed ASHA-Nutrition R01 study of antiretroviral (ART) adherence, the investigators trained lay community health workers, named Accredited Social Health Activist (ASHA), to improve the health of 600 rural WLH by providing emotional support, skill-building, nutrition education, and/or protein-enriched food supplements. In that study, our intervention, co-delivered by our trained ASHA, and guided by nurses, led to increased CD4+ T cell recovery and improved anthropometric and psychosocial outcomes. The investigators found that ASHA support plus protein supplements and nutritional education were significantly associated with improved CD4 counts and increased lean mass at 18 months (P \< 0.001), as well as significant improvements in depression, ART adherence, social support and internalized stigma. In our sub study, CC screening of 598 of these WLH revealed that 13% were found to have abnormal cervical lesions and 4 (1%) had squamous CC. Preliminary evidence also revealed that nutritional supplements may be associated with a 40% reduction in the risk of abnormal cervical lesions (adjusted odds ratio \[aOR\] = 0.60), with an association between serum albumin and reduced risk of abnormal lesions (aOR= 0.39). With a focus on secondary prevention of CC, the investigators hope to mitigate the link between HR-HPV persistence and risk of CC as well as improve the health of women co-infected with HPV/HIV (W-Co-V). Our stellar team plans to build upon our prior ASHA-Nutrition intervention, using formative research to refine a nurse-led, ASHA co-delivered, nutrition-enhanced SAKHI HPV intervention, adapted for W-Co-V. This will be followed by a randomized controlled trial (RCT), assessing the efficacy of our refined comprehensive, multifaceted SAKHI HPV intervention, as compared with an enhanced Standard of Care (SOC+) (usual care + 3 sessions \[wellness, basic nutrition and HPV/HIV health promotion\]) among 348 high-risk co-infected women to prevent CC while remaining engaged in the HIV treatment cascade, and managing nutritional health. Recruited participants will be individually randomized in a 1:1 ratio into the two study arms. Our Primary outcome is HR-HPV persistence (2 positive tests for the same HR-HPV type, separated by 12-18 months). The two aims incorporating RCT interventions are as follows: Aim 2. To evaluate the efficacy of SAKHI HPV intervention among 348 W-Co-V on the primary outcome (HR-HPV persistence) as compared to the Enhanced Standard of Care (SOC+) program. H2: Compared to the SOC+ participants, SAKHI participants will have lower rates of HR-HPV persistence. Aim 3. Assess the impact of the SAKHI program secondarily on: 1) HIV indices (HIV viral load; CD4 count); 2) Nutritional index (serum albumin) at 6-, 12-, and 18-months.

A Study of BMS-986340 as Monotherapy and as Combination Therapy in Participants With Advanced Solid Tumors

The purpose of this study is to assess the safety, tolerability, and recommended dose(s) of BMS-986340 as monotherapy and in combination with nivolumab, docetaxel, or Pumitamig in participants with advanced solid tumors. This study is a first-in-human (FIH) study of BMS-986340 in participants with advanced solid tumors.

Impact of an Educational Physiotherapy-Yoga Intervention on Perceived Stress in Women Treated With Brachytherapy for Cervical Cancer

Every year in France, nearly 3,000 women develop a cervical cancer. The average age of women diagnosed is 51. Uterovaginal brachytherapy is one of the reference treatments. To allow this treatment, an applicator is first placed under general anaesthesia in the vaginal zone. Then, the pulsed Dose Rate (PDR) or high dose rate (HDR) uterovaginal brachytherapy requires 2-5 days hospitalization in an isolated room. Uterovaginal brachytherapy requires strict bed rest without movements allowed for the pelvic area until the applicator is removed. Prolonged immobilization, the context of the illness and the intimacy of the area to be treated are all recognized sources of anxiety. According to a study, 40% of patients have post-traumatic stress at 3 months of treatment. A Danish team highlights the significant decrease in physical capacity during and after treatment. Thus, as a recent literature review concludes, there is a real need to develop Non-Pharmacological-Interventions (NPI) to limit the aftereffects. It also seems important to provide support for self-management of symptoms. Among NPI of interest, Yoga is a mind-body practice that can decrease perceived stress. A systematic review confirms that yoga can reduce stress during cancer treatment. This underlines the importance of proposing this practice for patients treated for all types of cancers and further evaluations on the effects of respiratory and meditation exercises. Another team showed the feasibility of respiratory exercise intervention in patients undergoing chemotherapy while also talking about mental health benefits. Finally, a reduction in perceived stress was achieved in women treated with radiotherapy for breast cancer through yoga intervention. A lot of work has been done with promising results without the result of a consensus applicable to all care situations. Moreover, educational requirements are high in women treated to gynecological cancer. Meeting these needs helps to improve quality of life, pain management and drug use. Integrating Patient Educational Project (PEP) therefore seems relevant as an additional tool in patient empowerment. In addition, the fact that a combined Physiotherapy-Yoga-PEP intervention is feasible in women treated for breast cancer allows us to offer adjusted version in patients with brachytherapy. The literature review thus invites us to propose the educational intervention Kine-Yoga-PEP in the very particular context of brachytherapy.

A First-in-Human Study of HH160 in Patients With Advanced Solid Tumors

This study is evaluating the safety, side effects, how the body processes HH160, and its early anticancer activity when given alone or with other cancer treatments in participants with advanced solid tumors. The study will also identify the recommended dose for future studies. The trial includes two phases and is expected to last about 4 years, with treatment and follow-up lasting approximately 6-12 months each.

Hugo™ Robotic-Assisted Surgery (RAS) System in Gynecological Subjects (Embrace Gynecology)

The purpose of this research is to evaluate the safety and performance of the investigational Medtronic Hugo™ Robotic Assisted Surgery (RAS) system when used during hysterectomy procedures, including patients being treated for cancer.

Effect of Web-Based Education on Attitudes and Beliefs About HPV Testing

Cervical cancer is a highly preventable public health issue that significantly impacts women's quality of life. Although effective screening programs such as Human Papilloma Virus (HPV) testing and Pap-smears are widely available, women's participation in these early detection services often remains limited. The primary barriers to screening attendance include insufficient education, lack of information, negative beliefs, psychosocial or cultural factors, and misconceptions regarding gynecological examinations. To improve screening uptake, health interventions must focus not only on increasing knowledge but also on promoting correct beliefs and positive attitudes toward testing. Web-based health education serves as an effective method to overcome barriers such as cost, transportation difficulties, and geographical limitations, allowing wider access to healthcare guidance. This study aims to evaluate the effects of a specialized web-based educational intervention on women's attitudes and beliefs regarding the HPV test. The research is designed as a randomized controlled trial with a pre-test and post-test design. Participants will be assigned to either an intervention group or a control group. The intervention group will receive structured health education through a dedicated web platform, while the control group will receive routine standard follow-up. Data will be gathered using a specific attitude and belief scale before and after the application to measure the intervention's impact.

Performance of SYMMCORA® vs. V-Loc® Suture Material in Patients Undergoing Laparoscopic Total Hysterectomy

The aim of this study is to show the superiority of the new unidirectional barbed suture (SYMMCORA® mid-term, unidirectional) to conventional suture material in terms of time to perform the vaginal cuff closure during gynecologic surgeries without an increase in the complication rate. Secondly, the superiority of SYMMCORA®, mid-term unidirectional compared to the V-Loc®, unidirectional will be assessed regarding the mean time to close the vaginal cuff. The study will be performed in routine clinical setting, the only difference will be the randomization into two different suture groups. Both suture materials which will be applied to approximate the vaginal cuff are approved and carrying the CE-marks. Additionally, both sutures will be applied in their intended use. Neither additional invasive measures nor additional burden in regard to the patient will be performed.

DESTINY-PANTUMOUR04

This study will evaluate the effectiveness of T-DXd in patients with HER2-positive (IHC 3+) locally advanced, unresectable, or metastatic solid tumors who have received prior systemic treatment for metastatic or advanced disease and have no satisfactory alternative treatment options in a real-world setting in the US

Novel, One Stop, Affordable, Point of Care and AI Supported System of Screening, Triage and Treatment Selection for Cervical Cancer in LMICs

Artificial intelligence (AI) is fast gaining reputation as a highly promising solution for cervical cancer screening. AI-based detection of cervical neoplasias is named automated visual exam (AVE) by the National Cancer Institute, USA. The investigators propose to develop and evaluate the performance characteristics of a novel AI system to both screen and triage women as well as help in treatment decision making. AI will analyse infrared spectroscopic signals derived from urine samples of unscreened women for the presence of high-risk human papillomavirus (hr-HPV). Our preliminary study has shown that spectroscopy can detect hr-HPV in urine. For screen-positive women the AI will interpret a set of cervical images captured with a high-quality devoted camera to detect high grade cervical precancers and cancers and to determine the type of transformation zone (TZ) (helps in treatment decision). The prototype device for image capture and the AI algorithms are already developed by us. The technologies will be further improved in part 1 (initial 2 years) and validated in part 2 (subsequent 3 years). During Part 1, the investigators will analyse urine samples collected from 1100 women at multiple screening clinics in Zimbabwe for the presence of hr-HPV using spectroscopy and use the signals generated to improve the AI algorithm. In this part the investigators will also assess the concordance between hr-HPV detection in urine samples using spectroscopy and cervical human papillomavirus (HPV) detection using a validated HPV test. The cervical image recognition device and the AI algorithm will be further improved during part 1 by collecting more images from hr-HPV positive and negative women. AI will also be trained to interpret the cervical images to determine the TZ type. In part 2 total 2100 women will be screened in Zimbabwe with AI-supported spectroscopic analysis of urine to detect hr-HPV and a validated HPV test to evaluate and compare their sensitivity and specificity to detect histology-proved high grade cervical precancers and cancers. The sensitivity and specificity of AI-supported detection of cervical neoplasias on cervical images will be evaluated to triage the HPV positive women. The accuracy of AI to determine TZ type will be compared with expert opinion. During the field validation part (part 2), the investigators will also conduct a cost analysis and compare cost of our approach to current standard Zimbabwean practice. The International Agency for Research on Cancer- World Health Organization WHO (IARC-WHO) has partnered with The Neo Sense Vector Company (NSV), Delaware, USA (industry), The Engineering Department, Lancaster University, Lancaster, UK and The University of Zimbabwe, College of Health Sciences, Harare, Zimbabwe to implement this study focusing on innovation that will greatly contribute to the global elimination of cervical cancer, a WHO priority.

People's Hospital of Xinjiang Uygur Autonomous Region

Objective: To evaluate the impact of enhanced recovery after surgery (ERAS)-based nursing intervention on venous thromboembolism (VTE) and lymphedema after radical hysterectomy for cervical cancer. Methods: In this prospective randomized controlled trial, 160 patients scheduled for radical hysterectomy during September 2022-September 2024 were randomized to an ERAS group (n = 80) or a control group (n = 80). The control group received conventional perioperative care, while the ERAS group received a multimodal perioperative care protocol. Primary outcomes were the 6-month incidence of VTE and lower limb lymphedema. Secondary outcomes included recovery indicators, inflammatory and coagulation markers, quality of life \[QoL; assessed by the Quality of Life Questionnaire-Core 30 (QLQ-C30)\], and nursing satisfaction.

Improving Muslim Women's Uptake of Cancer Screening (IMCAN)

The goal of this non-randomised trial is to test how a workshop that includes religiously-tailored messages can help increase the uptake of breast, colorectal and cervical cancer screening among Muslim women in North East England and Scotland. The results of this trial will inform the development of a full-scale randomised-controlled trial. Participants in this study will be asked to take part in a two-hour workshop, deliver either online or in-person.