Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Uterine Cervical Neoplasms

Carcinoma

Carcinoma in Situ

Uterine Cervical Dysplasia

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Precancerous Conditions

Cervical Intraepithelial Neoplasia

Lipid Regulating Agents

All Drugs and Chemicals

Fenofibrate

Hypolipidemic Agents

Antimetabolites

Participants with high-grade dysplasia will receive 200mg of Fenofibrate starting on the day of enrollment and will continue the drug administration daily for 2-4 weeks +/- 7 days until their excisional procedure

Participants with invasive cervical cancer will receive 200mg of Fenofibrate starting on the day of enrollment and will continue the drug administration daily for 2-4 weeks +/- 7 days until their definitive hysterectomy or chemoradiation

Fenofibrate is an FDA approved drug for cardiovascular indications and have decades of data supporting a favorable safety profile event with chronic use.

Cold knife conization or loop electrosurgical excision to remove cells and tissue in the cervix

Cervical Conization

In a hysterectomy, the uterus, cervix, both ovaries, both fallopian tubes, and nearby tissue are removed.

Hysterectomy

Chemotherapy uses anti cancer (cytotoxic) drugs to destroy cancer cells. The drugs circulate throughout the body in the bloodstream. Radiotherapy uses high energy waves similar to x-rays to kill cancer cells.

Chemoradiation

Lindsay A Ferguson, MD

Lindsay Ferguson, MD

Normally, p53 helps prevent tumors from forming in the body. Early studies have shown that Fenofibrate, a cholesterol-lowering drug, can restore normal function to p53 and can change the metabolism of HPV-positive tumors in a way that stops the growth of tumors. The purpose of this study is to understand how Fenofibrate can be used to treat HPV-positive cervical cancers and cervical dysplasia. Researchers will examine collected tissue samples and investigate various genes and proteins to see whether Fenofibrate has an effect on HPV-positive cervical cancers and cervical dysplasia.

Fenofibrate in Patients With Cervical Intraepithelial Neoplasia and Invasive Cervical Carcinoma

Window of Opportunity Trial of Fenofibrate in Patients With High-grade Cervical Intraepithelial Neoplasia and Invasive Cervical Carcinoma

Changes in p53 levels from initial biopsy to repeat sampling at the time of surgery

Changes in tumor metabolic status from initial biopsy to repeat sampling at the time of surgery evaluated via immunohistochemical testing

Assess tolerability of fenofibrate by comparing lab values at baseline to values at conclusion of treatment

Principal Investigator

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Subjects diagnosed with invasive cervical cancer

Cervical samples will be tested for histopathology diagnosis and human papillomavirus deoxyribonucleic acid testing.

Testing of archived cervical cancer tissue samples

Data collection

GSK Clinical Trials

The aim of this study is to assess the distribution of the most frequent types of human papillomavirus in women diagnosed with invasive cervical cancer in New Zealand.

Human Papillomavirus (HPV) Type Distribution in Adult Women Diagnosed With Invasive Cervical Cancer in New Zealand

Hospital-based Epidemiological Study on the Distribution of Human Papillomavirus (HPV) Types in Adult Women Diagnosed With Invasive Cervical Cancer (ICC) in New Zealand

GlaxoSmithKline

Women who screen positive for pre-cancer lesions of the cervix will be offered treatment with thermal ablation and the process of implementation evaluated using implementation science RE-AIM framework

Thermal ablation is based on local heating (around 100 degrees centigrade), applied for 20 to 60 seconds to destroy abnormal tissue by burning and inducing necrosis of pre-cancer and surrounding tissue. It has been used in by gynecological surgery for over 50 years, proven safe and easy to use by middle level health care providers in primary care settings.

Thermal Ablation

Lynda Oluoch, MBChB, MPH

Jason Caucutt

Lynda Oluoch, MD

Catherine Kiptiness

Nelly Mugo, MPH, MMed

Global elimination of cervical cancer is a feasible goal; however, the countries with the greatest disease burden also have the greatest healthcare system challenges. Cervical cancer (CC) is almost entirely preventable, yet, it remains the 2nd most common cause of cancer and is the most common cause of cancer deaths among women in the majority of Low-Middle-Income-Countries (LMIC) including Kenya. Effective low-cost interventions for early detection of pre-cancer lesions have been available but there remains very low coverage with about 16% eligible women screened in Kenya. Cryotherapy has been introduced as a low-cost intervention for treatment of pre-cancer lesions, however, challenges with equipment shortage, costs, supply chain difficulties of refrigerant gas and equipment failure health facilities has been cited as a reason for the low treatment rates of screen positive women. In Kenya only about 30% of women screening positive access treatment for the pre-cancer lesions. This project will introduce thermal ablation (TA), which is proven to be safe and as effective as cryotherapy for treatment of pre-cancer lesions of the cervix. TA uses electricity, batteries or solar to charge, takes a shorter time to use, is a small easily portable equipment.

The primary aim of the study is to deliver, evaluate and cost implementation of the 'Single Visit Screen and Treat with Thermal Ablation' (SVA-SAT+TA) intervention for treatment of women who screen positive for pre-cancer lesions of the cervix in reproductive health clinics in Kenya, using implementation science framework to inform National scale-up.

To achieve national and global goals to eliminate cervical cancer, there is an urgent need to adapt, implement, and scale-up effective technologies in Kenya. The proposed research project will develop a contextually appropriate implementation and dissemination model to guide effective scale-up of the single visit screen and treat approach with use of thermal ablation to health facilities to bridge access to cervical cancer prevention services for women in Kenya and similar low resource settings.

The mainstay of cervical cancer (CC) prevention in low- and middle-income counties (LMIC) has been the single-visit approach with screen-and-treat (SVA-SAT) method, using visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy to manage precancerous lesions. It is a low-cost screening approach and minimizes loss to follow-up compared to traditional cytology. In Kenya, there is extremely low fidelity of SVA-SAT. Thermal ablation (TA) is an effective alternative to cryotherapy for ablation of precancerous lesions, and has been recommended by the World Health Organization (WHO) since 2019. Preliminary data from an investigative team member demonstrated safety, effectiveness, and acceptability to women when delivered by nurses in Zambia and Kenya. The portable device can be charged with electricity, batteries or solar panels, which is ideal for low-resource settings. Successful implementation and scale-up of TA within the SVA-SAT approach could optimize CC prevention.

This is a five-year prospective, stepped-wedge, cluster randomized trial to implement SVA-SAT+TA in 10 reproductive health (RH) clinics in central Kenya. The study uses mixed-methods evaluation based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework to assess the intervention's impact.

In collaboration with multi-level (clinic, county, national) stakeholders this project will develop a sustainable D\&I strategy and leverage trial implementation to include costing and budget impact analysis. The objective is to develop and evaluate a locally contextualized dissemination and implementation (D\&I) strategy for SVA-SAT with TA (SVA-SAT+TA) to inform national scale-up. The hypothesis is that TA will enhance the feasibility, adoption, and sustainability of CC prevention services via SVA-SAT, compared to the standard of care with cryotherapy.

Design:

Prospective, stepped-wedge, cluster randomized trial to implement SVA-SAT+TA in ten reproductive health (RH) clinics in central Kenya.

Population: Mixed population: Reproductive health care workers, health manager's, women seeking services for cervical cancer screening and women who screen positive for pre-cancerous lesions of the cervix.

Objective 1:

Develop a dissemination and implementation strategy to introduce SVA-SAT+TA that effectively accounts for the heterogeneity of the client, provider, and system inputs.

Approach: The project will use qualitative interviews with women seeking CC prevention services, reproductive health (RH) providers, RH managers, and key program stakeholders to identify actionable barriers and facilitators to SVA-SAT+TA uptake. These data will be presented at a stakeholder workshop to synthesize and contextualize strategies to effectively introduce the intervention and provide guidance for scale up.

Objective 2:

Deliver the SVA-SAT+TA intervention at scale in RH clinics and evaluate implementation using the RE-AIM framework.

Approach: The SVA-SAT+TA will be introduced into RH clinics using a stepped-wedge study design and using RE-AIM framework the process will be rigorously evaluated on how effective it is disseminated and implemented. Key endpoints will include:

1. (REACH) Proportion of the clinics reached, providers trained;
2. (EFFECTIVENESS) Intervention effect on SVA-SAT process measures: number of screen positive women identified per month, treatment completion rate compared to pre-intervention, and the patient-level TA fidelity of implementation assessed by testing Human Papillomavirus (HPV) clearance
3. (ADOPTION) Proportion of the clinics incorporating TA into routine care
4. (IMPLEMENTATION) Describe drivers of success/failure using the Consolidated Framework for Implementation Research (CFIR)
5. (MAINTENANCE) Proportion of clinics that continue to provide and sustain SVA-SAT+TA services post intervention implementation.

Objective 3:

Compare the cost and budget impact of SVA-SAT+TA to SVA-SAT using cryotherapy. Approach: Using micro-costing techniques to quantify the programmatic costs of SVA-SAT with cryotherapy and with TA.

Using implementation science methods to evaluate the implementation of thermal ablation for treatment of pre-cancer lesions of the cervix in reproductive health clinics

Cervical Cancer Elimination -Using Implementation Science to Evaluate Deliver and Cost Introduction of Thermal Ablation

Implementation and Scale Up of a Single-visit, Screen-and-treat Approach With Thermal Ablation for Sustainable Cervical Cancer Prevention Services in Kenya

De-identified provider interviews will be shared with other Implementation Science researchers to improve healh care outcomes.

Using a participatory approach through engagement of key stakeholders (women seeking cervical cancer prevention services, frontline health care workers, managers and policy makers) describe factors that deter successful introduction and scalability of SAT-SVA+TA intervention

Using a participatory approach through engagement of key stakeholders (women seeking cervical cancer prevention services, frontline health care workers, managers and policy makers) describe factors that make it suitable for successful introduction and scalability of SAT-SVA+TA intervention

The number of providers trained who continue to provide treatment for pre-cancer lesions of the cervix using thermal ablation with a single visit approach during the periods before, during and after introduction of TA to RH clinics

Measure treatment completion rate compared to pre-intervention for women who screen positive for pre-cancer lesions of the cervix

The treatment completion rates of women with pre-cancer lesions of the cervix after withdrawal of active implementation support by project personnel

The number of screen positive women treated with TA that clear HPV infection post treatment

Quantify the programmatic costs of SVA-SAT for treatment of pre-cancer lesions of the cervix.

National Cancer Institute (NCI)

Kenya Medical Research Institute

University of Washington

Research Associate Professor: Global Health

Women randomised to this arm get primary HPV testing

women included follow the standard procedure with primary cytology

HPV testing

Joakim Dillner, MD, PhD

The purpose is to evaluate whether implementation of primary human papillomavirus (HPV) screening in the screening programme for cervical cancer improves the programme in terms of better cancer protection and better cost efficiency.

Primary HPV screening is a method with higher sensitivity than cytology for detection of high-grade cervical intraepithelial neoplasia, which is the precursor of cervical cancer. In particular, HPV test is a better test for revealing adenocarcinomas, since these cancers often show a normal cytology.

Cytology is less effective in older women, and screening with cytology in women over 60 has no documented effect. Today a large part of cervical cancer develop in women older than 60, to whom no screening is offered. The prevalence of HPV is around 4% in this age group. Since we know that testing negative for HPV gives a better long-term protection against cervical cancer compared to cytology, primary screening for HPV in 60-year old women would give a longer lasting protection in this high-risk group compared with today.

HPV screening is most cost effective above 35 years of age. The reason for this is that HPV is less prevalent at age 35 than in younger women and also because cervical cancer seldom develops before this age. Since the HPV test has a negative predictive value (NPV) of almost 100% this could lead to longer screening intervals, which would be improve cost-effectiveness.

Randomized Implementation of Primary HPV Testing in the Organized Screening for Cervical Cancer in Stockholm

Randomized Implementation of Primary Human Papillomavirus (HPV) Testing in the Organized Screening for Cervical Cancer in Stockholm

The number of women with CIN2+ detected by primary HPV testing will be compared with the number of women with CIN2+ detected by primary cytology

The cost for the new procedure with HPV test in primary screening will be compared to the routine procedure with primary cytology

The number of women with invasive cervical cancer detected in the two arms.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fenofibrate in Patients With Cervical Intraepithelial Neoplasia and Invasive Cervical Carcinoma	NCT06191133	Cervical Intrae... Invasive Cervic...	Fenofibrate Cervical Coniza... Hysterectomy Chemoradiation	18 Years -	Case Comprehensive Cancer Center
Human Papillomavirus (HPV) Type Distribution in Adult Women Diagnosed With Invasive Cervical Cancer in New Zealand	NCT01328028	Cervical Cancer	Testing of arch... Data collection	18 Years -	GlaxoSmithKline
Human Papillomavirus (HPV) Type Distribution in Adult Women Diagnosed With Invasive Cervical Cancer in New Zealand	NCT01328028	Cervical Cancer	Testing of arch... Data collection	18 Years -	GlaxoSmithKline
Fenofibrate in Patients With Cervical Intraepithelial Neoplasia and Invasive Cervical Carcinoma	NCT06191133	Cervical Intrae... Invasive Cervic...	Fenofibrate Cervical Coniza... Hysterectomy Chemoradiation	18 Years -	Case Comprehensive Cancer Center
Cervical Cancer Elimination -Using Implementation Science to Evaluate Deliver and Cost Introduction of Thermal Ablation	NCT05472311	Cervical Cancer	Thermal Ablatio...	21 Years - 60 Years	University of Washington
Randomized Implementation of Primary HPV Testing in the Organized Screening for Cervical Cancer in Stockholm	NCT01511328	High-grade Cerv... Invasive Cervic...	HPV testing	30 Years - 64 Years	Karolinska Institutet

Spots Global Cancer Trial Database for invasive cervical cancer