Cervical Cancers

This is a prospective non-randomized clinical trial to evaluate the feasibility of 3 fraction versus a standard 4 fraction high dose rate brachytherapy regimen in patients with locally advanced cervical cancer.

The purpose of the Unidos Contra el VPH study is to help find options to screen, or check, for cervical cancer that individuals can do at home to help prevent and detect cervical cancer early. Usually, people get screened for cervical cancer with a Pap smear and human papillomavirus (HPV) test by a health care provider. This is not always easy for individuals who are not able to get to a clinic or feel uncomfortable having the procedure done. That is why we want to find other ways that may be easier and more comfortable for people to be screened for cervical cancer. The two main questions the study aims to answer are: 1. How do the following three cervical cancer screening methods compare for improving screening completion rates? o In-home HPV self-sampling with a vaginal swab * In-home HPV self-sampling with urine testing * In-clinic traditional Pap smear with HPV test 2. What are participant beliefs and preferences regarding these three screening methods? Participants in the study will be randomly assigned to one of three groups. This means each person has an equal chance of being placed in any group. They will also complete two surveys as part of the study. The three screening method groups are described below: Group 1: Urine Self-Sampling * Participants in this group will receive a kit with a urine sample cup to use at home, instructions explaining how to take the sample and a pre-paid mailing box to mail the urine sample to the lab. Group 2: Vaginal Swab Self-Sampling o Participants in this group will receive a kit with a vaginal swab and collection tube to use at home, instructions explaining how to take the sample and a pre-paid mailing box to mail the sample to the lab. Group 3: In-Clinic Screening * An in-clinic co-testing appointment is scheduled for a Pap smear and HPV test done together at Project Vida Health Center. By comparing these approaches, this study aims to improve access to cervical cancer screening and provide better options for those who face barriers to clinic-based screening.

This is an open-label, dose escalation, multicenter, phase 1, first-in-human study of XNW28012 in subjects with advanced solid tumors who have failed current standard anti-tumor therapies or are intolerant to such therapies. The study consists of two parts: a dose escalation part and a dose expansion part.

This is a Phase I clinical trial evaluating an investigational treatment called IDOV-Immune, a type of oncolytic virus therapy, for adults with advanced solid tumors that have not responded to standard treatments. Oncolytic viruses are designed to infect and destroy cancer cells and have the potential to stimulate the immune system to fight the tumor. The purpose of this study is to determine the safety of IDOV-Immune, how well it is tolerated, and to identify the highest dose that can be safely given. Researchers will also study how the drug behaves in the body, how the immune system responds to it, and whether it shows any signs of shrinking tumors. Participants will receive a single intravenous (IV) infusion of IDOV-Immune and will be closely monitored for side effects and any changes in their cancer. This study is being conducted at multiple sites in the United States and Australia.

The purpose of this study is to validate Automated Visual Evaluation (AVE), specifically the CINFinder version developed by DL Analytics, a point-of-care screening and triage diagnostic tool for cervical cancer based on the assessment of digital images through artificial intelligence. Several teams around the world have developed versions of AVE as a triage technology but none as a screening tool.

A Phase II Study of Serplulimab Plus Chemoradiotherapy as Adjuvant Treatment for Postoperative Cervical Cancer with Multiple Risk Factors

The goal of this open-label randomized control trial is to study the effect of immunonutrition in locally advanced cervical cancer (LACC) with standard concurrent chemoradiotherapy. LACC patients undergoing radical synchronous chemoradiotherapy will be randomized into the experimental group receiving enteral immunonutrition therapy and the control group receiving standard enteral nutrition support.The main purpose it aims to answer are:1）Can immunonutrition therapy improve patients' dose-limiting toxicity(DLT) and DLT-free survival? 2）Can immunonutrition therapy improve patients' nutritional status and quality of life?

This is a double-blind randomized controlled trial of 420 non-pregnant women undergoing cancer screening by visual inspection with acetic acid (VIA) who have Type 3 transformation zone (TZ) and randomized to receive either Misoprostol or placebo.

Cervical cancer ranks fourth globally in both incidence and mortality rates, making early diagnosis and treatment of great significance. For early-stage cervical cancer, surgery remains the primary treatment approach. According to the latest NCCN guidelines, patients with Stage IA2 or IB1 cervical cancer confirmed by cone biopsy who meet Concerv or SHAPE criteria no longer require type C/B hysterectomy. Instead, they may undergo type A hysterectomy with reduced surgical margins. However, patients with Stage IB2 or IIA1 tumors measuring 2-4 cm still require radical hysterectomy (type C). Radical hysterectomy carries high risks of postoperative complications and significantly impairs quality of life, including major vascular injury, urinary tract damage and dysfunction, lymphatic complications, and sexual dysfunction. Therefore, there is an imperative need to explore alternative or refined treatment approaches for Stage IB2/IIA1 cervical cancer that ensure survival outcomes while reducing surgical morbidity and improving quality of life. Neoadjuvant therapy followed by scale-reduced surgery may represent a feasible strategy. Both immune escape and angiogenesis are core drivers of tumorigenesis and progression. Combined immunotherapy and anti-angiogenic therapy have demonstrated favorable antitumor efficacy and manageable safety profiles across multiple tumor types. Ivonescimab is a novel humanized tetrameric IgG-scFv bispecific antibody targeting PD-1 and VEGF. Mechanistically, PD-1 blockade reverses T-cell suppression while VEGF inhibition curbs neovascularization, yielding synergistic therapeutic enhancement. This agent has shown promising efficacy and safety in advanced non-small cell lung cancer, hepatocellular carcinoma, and recurrent glioblastoma, though clinical data in cervical cancer remain absent. Therefore, this prospective exploratory study aims to evaluate the efficacy and safety of neoadjuvant Ivonescimab combined with paclitaxel and cisplatin followed by type A hysterectomy for stage IB2/IIA1 cervical cancer. The findings may provide novel insights for optimizing treatment paradigms-ensuring survival outcomes while preserving quality of life.

Solid cancers are frequently treated with chemotherapies that target the DNA of cancer cells. It has recently come to light that bacteria are also the target of chemotherapies used in oncology. The results of current studies demonstrate the close link between the composition of the microbiota, the immune system, toxicity and the efficacy or otherwise of anti-cancer treatments. In this context, the study will measure the influence of treatment with anticancer molecules known to activate the bacterial SOS response on the emergence of antibiotic-resistant commensal bacteria in the gut microbiota of cancer patients. Furthermore, this study will investigate the existence of a close link between changes in the intestinal microbiota determined by the induction or non-induction of the SOS response, bacterial translocation, the integrity of the intestinal barrier and the antitumor immune response. The RAMA trial plans to collect stool and blood samples from two different cohorts of patients: * Unexposed cohort: patients receiving anti-cancer treatment that does not induce bacterial SOS response. * Exposed cohort: patients receiving anti-cancer treatment inducing the bacterial SOS response. Patients' stools will be collected within 7 days of their first chemotherapy treatment and within 7 days of the 3rd chemotherapy cycle. Two blood samples will be taken at the same time as the stool samples. The results obtained from this prospective clinical research will then be investigated in two experimental laboratory models. The aim is to demonstrate that cytotoxic anticancer drugs promote the emergence of antibiotic-resistant commensal bacteria, by means of this large-scale study comprising a clinical component, which is the subject of the research presented in this protocol, combined with laboratory research components.

The aim of this clinical trial is to assess the oncologic safety of minimally invasive pelvic exenteration in patients with recurrence or persistence of cervical or vaginal cancer with pelvic location, suitable for pelvic exenteration according to the ESGO guidelines (European Society of Gynecological Oncology). The primary aim is to assess the 3-year disease-free survival (DFS). The secondary aim is to assess the 3-year overall survival (OS), the intraoperative and post-operative complication rate, and the patient's quality of life.

This is a Phase 1/2, multi-center, open-label, dose-escalation and expansion study to evaluate safety and tolerability, PK, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors.

This is a prospective, single-arm, Phase II clinical trial designed to evaluate the efficacy and safety of paclitaxel and carboplatin combined with PD-1/PD-L1 immune checkpoint inhibitors in the treatment of locally advanced cervical cancer. Using single-cell RNA sequencing (scRNA-seq), the study aims to investigate the molecular mechanisms underlying differential treatment responses and optimize personalized therapeutic strategies. Eligibility Criteria: Patients with locally advanced cervical cancer (FIGO stages IB3 to IIB) and a primary tumor diameter \>4 cm will be enrolled. All patients must have histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or common adenocarcinoma, an ECOG performance status of 0-1, and no prior treatment. Outcome Measures: * Primary endpoint: Objective response rate (ORR), assessing tumor regression. * Secondary endpoints:Overall survival (OS), progression-free survival (PFS), and incidence of treatment-related adverse events (graded by CTCAE criteria). * Exploratory endpoint:\*\* Impact of treatment on the tumor microenvironment and gene expression profiles. Study Intervention: All patients will receive three cycles of paclitaxel and carboplatin chemotherapy combined with PD-1/PD-L1 inhibitor therapy, followed by open radical hysterectomy and pelvic lymphadenectomy. Postoperative adjuvant therapy (chemotherapy, chemoradiation, or maintenance immunotherapy) will be determined based on pathological assessment. Tumor tissue samples will be collected during treatment for single-cell sequencing analysis. Sample Size: The study plans to enroll at least 34 eligible patients. Based on treatment response, patients will be categorized into high-response and low-response groups, with a minimum of 5 cases per group selected for scRNA-seq to ensure robust molecular mechanism analysis. The sample size calculation assumes a historical ORR of 65% and a target ORR of 85%.

Nerve-sparing radical hysterectomy aims to preserve the autonomic innervation of pelvic organs. In most studies, the preservation of the parasympathetic component of pelvic innervation is achieved by sparing the lymphovascular-neural tissue located at the base of the lateral paracervical tissue. This study explores an alternative surgical technique based on a different anatomical pathway of parasympathetic fibers, running more cranially and deeply within the pararectal space.

Women's knowledge, attitudes and behaviors about cancer are very important in the prevention of cervical cancer. In addition to medical interventions, psychosocial support and education programs are of great importance in the fight against cancer. Peer support helps individuals going through the same disease process to exchange information and emotional support by sharing their experiences with each other. In addition, the information obtained through peer support provides more permanent learning in individuals due to the transfer of information based on similar experiences and the creation of more trust and empathy compared to traditional education methods. Peer-supported education programs for women diagnosed with cervical cancer not only provide theoretical knowledge but also support the applicability of this knowledge in daily life. The trainings address topics such as risk factors of cervical cancer, the importance of HPV vaccination, the necessity of regular screening tests and healthy lifestyle behaviors, including attitudes towards cervical cancer prevention and cancer-related information. It is very important that this information is not limited to individual learning and that it is discussed within the group and supported by experiences through peer support, in order to increase the level of knowledge.

The goal of this clinical trial is to test an mHealth intervention for cervical cancer prevention in under-screened women ages 25-64 on the Caribbean Coast of Nicaragua. The mHealth intervention combines a patient-centered mobile app, a provider portal, and connectivity to the National Breast and Cervical Cancer Surveillance System (SIVIPCAN). The mHealth intervention will be combined with HPV primary screening for cervical cancer. The main questions it aims to answer are, when integrated into an HPV-based screening program: Is the mHealth intervention acceptable? Is the mHealth intervention feasible? Researchers will compare the intervention group (mHealth intervention) to the control group (standard care). Participants will: Receive HPV-based cervical screening. Intervention group: Through the patient-centered app, participants will receive "results ready" notification and navigation to the clinic for follow-up. Control group: Participants will receive "results ready" notification and navigation to the clinic for follow-up through existing communication channels.

Currently, the survival rate of locally advanced cervical cancer is low, posing a significant challenge in the treatment of cervical cancer. Radical chemoradiotherapy is considered the standard treatment for patients with locally advanced cervical cancer. However, 23.3% to 34.4% of patients still experience recurrence or subsequent metastasis. Radical surgery following neoadjuvant chemotherapy is an alternative to concurrent chemoradiotherapy, but it also has limitations: for approximately 9.8% to 30.6% of patients who do not respond to neoadjuvant chemotherapy, effective local treatment may be delayed. Additionally, more than 30% of patients still require adjuvant radiotherapy or chemoradiotherapy after surgery, significantly increasing the risk of complications. Therefore, there is an urgent need to explore alternative or improved treatment methods for neoadjuvant chemotherapy in locally advanced cervical cancer. An increasing number of women are being diagnosed with cervical cancer during their childbearing years, many of whom have a desire to preserve their fertility. For selected patients with stage IB2 cervical cancer, options include abdominal radical trachelectomy or radical trachelectomy following neoadjuvant chemotherapy. However, compared to conservative surgeries such as conization or partial cervical resection, radical trachelectomy is associated with less favorable fertility rates and pregnancy outcomes, with significantly higher rates of infertility, miscarriage, and preterm birth. For patients with stage IB3 or IIA1-IIA2 cervical cancer, the current standard surgical approach is radical hysterectomy, which does not preserve fertility. Current research suggests that neoadjuvant chemotherapy can shrink tumor size, decrease lymph node and distant metastases, and reduce the need for postoperative adjuvant radiotherapy. This offers hope for young cervical cancer patients who wish to preserve fertility, as it may reduce tumor size, thereby allowing for less extensive fertility-sparing surgery, improving pregnancy outcomes, or even making fertility-sparing surgery a viable option. In recent years, immunotherapy has gradually become a research hotspot in cancer treatment. Anti-PD-1/PD-L1 monoclonal antibodies, as a type of immunotherapy drug, have demonstrated promising anti-tumor efficacy and low side effects in clinical trials. Iparomlimab and Tuvonralimab is a novel therapeutic biological product targeting both PD-1 and CTLA-4. It is composed of two engineered monoclonal antibodies (anti-PD-1 and anti-CTLA-4) expressed in a fixed ratio and has shown significant efficacy in cervical cancer patients. Therefore, given the urgent need to improve neoadjuvant therapy for locally advanced cervical cancer and fertility-preserving neoadjuvant therapy for early-stage cervical cancer patients, this study is being conducted to explore and evaluate the efficacy and safety of Iparomlimab and Tuvonralimab combined with paclitaxel and cisplatin as neoadjuvant therapy for cervical cancer. Additionally, the study aims to investigate the relationship between tumor-related biomarkers and the risk of recurrence.

The goal of this study is to evaluate if indocyanine green (ICG) fluorescence imaging helps reduce complications in bowel surgery performed during gynecologic cancer operations. The main question it aims to answer is: Does using ICG fluorescence imaging during bowel anastomosis reduce the rate of complications such as leaks, infections, and abscesses within 30 days after surgery? Participants are women aged 18 and older undergoing surgery for gynecologic cancers (such as ovarian, uterine, cervical, or vulvar cancer). During surgery, investigators will inject ICG intravenously, then use a special near-infrared camera to see how well blood flows at the anastomosis site. The investigators will then decide if the reconnection is good enough or needs adjustment. Researchers will record any complications within the first 30 days after surgery to understand if this imaging method helps reduce surgical risks.

This is a multicenter, open-label Phase IIa clinical study to evaluate the efficacy and safety of B1962 in the treatment of ad-vanced solid tumors. The study consists of a Screening Period, a Treatment Period, and a Follow-up Period (EOT Visit, Safety Follow-up, and Survival Follow-up). Subjects who meet the inclusion criteria and do not meet the exclusion criteria at screening will enter the appropriate study co-hort according to tumor type and receive B1962 until unacceptable toxicity, radiographic disease progression, or withdrawal of the sub-ject for other reasons, whichever comes first, for a maximum of 24 months of treatment. Enrollment will be conducted according to three stages: Stage I: It is planned to enroll 5 patients in each of 8 cohorts (tumor type) to observe the safety and efficacy; Stage II: 1 \~ 2 cohorts are preferred to enroll 15 \~ 20 patients to observe the ef-ficacy and safety; Stage III: 1 cohort is finally preferred to continue enrollment until a total of no more than 60 patients are observed in this cohort to observe the efficacy and safety.

The zinc monoterpenoid tetra-ascorbo-camphorate possesses broad-spectrum anti-viral properties in vitro, particularly against HIV, HSV and HPV. Its C14 formulation could be a promising candidate for in vivo clinical evaluation as a potential microbicide or therapeutic drug. The aim of this clinical trial is to determine whether C14 is effective in reducing the genital viral load of HR-HPV and in treating low-grade dysplastic lesions of the cervix. It will also determine the tolerability of C14. The main questions to be answered by the clinical trial are as follows: Does C14 reduce the genital HR-HPV viral load in participants with persistent HR-HPV infections? What medical problems do participants experience when taking C14? Researchers will compare C14 to a placebo (a similar substance that contains no drug) to see if C14 is effective in reducing genital C14 viral load and in treating low-grade dysplastic lesions of the cervix. Participants will receive four monthly treatments (5ml of C14 dissolved in distilled water administered twice daily \[morning and evening\] for seven days via vaginal syringe during the follicular phase) of C14 or placebo for 4 months and visit the clinic once every 2 weeks for examinations and tests. They will keep a diary of their symptoms and the number of times they keep the hospital appointment.