Clinical trial NCT04735445: IMPACt of an Enhanced Screening Program on the Detection of Non-AIDS NEOplasms in HIV Patients
Official title: IMPACt of an Enhanced Screening Program on the Detection of Non-AIDS NEOplasms in Patients With Human Immunodeficiency Virus (HIV) Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: HIV/AIDS
Cancer
Keywords: HIV
Neoplasm
Screening
Early diagnosis
Lead sponsor: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
name: Hospital General Universitario Reina Sofía de Murcia
name: Hospital Universitario Reina Sofia de Cordoba
name: Hospital General Universitario de Alicante
name: Hospital Clinic of Barcelona
name: Hospital Universitario Ramon y Cajal
name: Hospital General Universitario Santa Lucia
name: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
name: Hospital Universitario de Guadalajara
name: Hospital Universitario Virgen de la Arrixaca
name: Parc Taulí Hospital Universitari
name: Hospital Universitario La Fe
name: Germans Trias i Pujol Hospital
name: Complejo Hospitalario Universitario de Albacete
name: Hospital Universitario Fundación Alcorcón
name: Hospital General Universitario Elche
First posted: 2021-02-03
Enrollment: 4638
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: Introduction: The incidence of malignancies is higher in the HIV-infected population than in the general population, and it is already one of the leading causes of death in people living with the virus. It is estimated that the situation will be aggravated by the progressive aging of the HIV-infected population. Early diagnosis through enhanced cancer screening can be critical in reducing mortality, but may increase expenditure and harms associated with adverse events. This strategy should then be considered only when the benefits clearly outweigh the harms. There are currently no studies on expanded cancer screening in patients with HIV, and available information from the point of view of costeffectiveness or cost-utility is scarce.

Hypothesis: An enhanced program for non-aids cancer screening in patients with HIV can lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions and being cost-effective.

Objectives: To evaluate the efficacy, safety and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard practice within the cohort of the National AIDS Research Network (CoRIS).

Specific objectives: 1) To compare the incidence of early diagnosed cancer with enhanced screening versus conventional screening; 2) To assess the incidence of early diagnosed cancer and its overall incidence in the CoRIS cohort; 3) To analyze safety of the program: adverse events and unnecessary interventions; 4) To compare the obtained data stratifying by gender and 5) To analyze the cost-utility of the program.

Expected results: 1) To generate scientific evidence to inform decision makers on the advisability of implementing an enhanced screening program of cancer in HIV-infected patients; 2) To broaden knowledge about the programs of early detection of cancer in vulnerable populations and their economic evaluation from the perspective of the National Health Service.

Detailed description: Non-AIDS-Defining Cancers (NADCs) are an important cause of morbidity and mortality in the population living with the human immunodeficiency virus (PLHIV), being currently one of the most frequent causes of death. Due to several reasons, the incidence of this type of tumors in PLHIV has increased 2-3 times with respect to the general population (GP). In a recent systematic review, with more than 600,000 PLHIV and 10,891 new cases of cancer, it is demonstrated how the incidence of NADCs has progressively increased since the introduction of combined antiretroviral therapy (ART), probably reflecting better viral-immune control and aging associated with the increase in overall survival of patients living with the virus. The most frequent cancers are lung cancer, hepatocellular carcinoma, anal carcinoma and cervical carcinoma, although some studies have suggested that there could also be a higher incidence and / or severity of other malignant tumors, such as breast cancer, prostate, colorectal or skin, including melanomas. In the era of ART, lung cancer has become the most frequent and deadliest cause of non-AIDS-associated cancer in PLHIV, and greater lethality has been documented in PLHIV than in GP.

The causes of this increased incidence of NADCs are not well known and there are several factors that could influence, including the oncogenic effects of the virus, immunosuppression, chronic inflammation and immune activation, ART exposure, higher rates of coinfection with other oncogenic viruses and traditional cancer risk factors such as smoking. It is estimated that at least 1 in 3 PLHIV will die due to malignant neoplasms in the coming years. There is currently no consensus on the best screening strategies in this population, strategies that seem increasingly necessary considering the progressive aging of the infected population and the increase in the incidence of these neoplasms.

In some of the clinical practice guidelines in PLHIV, such as the Spanish Gesida or other European ones, the screening strategies for neoplasms recommended in GP have been incorporated, in which they have shown benefit in terms of mortality or greater probabilities of therapeutic success. However, these benefits have not been confirmed in PLHIV, in which this type of strategy could be insufficient.

Moreover, there are currently no established recommendations for GP screening on two of the main neoplasms of PLHIV, such as lung and anal. For this reason, it is necessary to generate scientific evidence that determines which is the most convenient strategy to reduce the morbidity and mortality associated with NADCs in PLHIV. Then, the evaluation of an enhanced program of screening by conducting a clinical trial, in which patients are randomized to one of the two strategies (enhanced screening versus standard of care practice), is the ideal design to generate scientific evidence. This knowledge could be useful to determine if the benefits of the enhanced screening outweighs the harms and if it is cost-effective for the National Health Service.

Objectives:

General objectives: To evaluate the efficacy, safety and efficiency of an expanded screening program for the early diagnosis of cancer in patients with HIV compared to usual practice, within the framework of the Spanish AIDS Research Network (RIS).

Specific objectives: 1) To compare the incidence of early diagnosed cancer with extended screening versus usual practice; 2) To estimate the incidence of early diagnosed cancer and its overall incidence in the CoRIS cohort; 3) To analyze safety of the program: adverse events and unnecessary interventions; 4) To compare the incidence data described above stratifying by gender and 5) To analyze the cost-utility of the extended screening.

Early detection of cancer would entail clinical benefits, both in terms of survival and quality of life, for the population with HIV. The evaluation of the cost-utility of the program is also a main objective, since the benefits of therapy for cancer in the earliest stages should compensate for the use of the additional resources of the National Health System.

Methodology: Research project that includes randomization by patient, stratified according to sex, to one of the following groups:

1. Enhanced intervention group: expanded screening for early detection of lung, liver, anal, cervical, breast, prostate, colorectal and skin cancer.
2. Conventional intervention group: standard screening in the participating centers, adjusted to the recommendations of the European AIDS Society (EACS).

Work plan and timeline

This project is based on a collaborative methodology in which all groups work in a coordinated manner, under the direction of the Principal Investigator, Dr. Félix Gutiérrez. The tasks that make up this project are broken down below:

1. Recruitment of patients and randomization according to the sex of each patient to a conventional intervention or an extended intervention. This phase is already started in some of the centers that make up the consortium, but it must continue to reach the desired sample size. Depending on whether the patients are assigned to the conventional screening group or the extended screening group, their inclusion in the following tasks will be different.
2. Completion of the questionnaires (annual) on sociodemographic and toxic data in each of the participating centers.
3. Blood samples withdrawal and storage of plasma for ulterior determination of biomarkers annually.
4. The digital examination and anal (semi-annual) cytology, cervical cytology (semi-annual) will be performed in the HIV Units of the participating centers.
5. The General Inspection in search of skin lesions suggestive of malignancy on an annual basis will be carried out in the HIV Units of the participating centers that will be previously trained for it. In case of suspicion, it will be referred to the specialist of each center.
6. The semi-annual monitoring of the clinical trial will be carried out by the CRO contracted for that purpose.
7. At 30 months, the telematic session for closing the trial will be held.
8. Statistical analysis of the data. The analysis of the data will be carried out transversely after the first year, after the second and after the third year, where the final conclusions of the study can be established.
9. Dissemination of the results during the last 3 months: communications to congresses and writing of articles. Proposal for inclusion in Clinical Guidelines.

Eligibility criteria: Inclusion Criteria:

* Male ≥40 years or woman ≥18 years
* Informed Consent signed

Exclusion Criteria:

* Active AIDS defining disease
* Antecedent of cancer
* Terminal disease
* Pregnancy or breastfeeding
* Patient rejection

Primary outcomes:
measure: Non-AIDS defining cancers incidence
timeFrame: through study completion, an average of 1 year
measure: Survival rate
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Safety of the screening: adverse events
timeFrame: through study completion, an average of 1 year
measure: Cost-efectiveness
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
state: Alicante
Study officials:
affiliation: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
name: Félix Gutiérrez-Rodero, PhD
role: PRINCIPAL_INVESTIGATOR
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