IMPACt of an Enhanced Screening Program on the Detection of Non-AIDS NEOplasms in HIV Patients

IMPACt of an Enhanced Screening Program on the Detection of Non-AIDS NEOplasms in Patients With Human Immunodeficiency Virus (HIV) Infection

Sponsors

Lead Sponsor: Felix Gutierrez

Collaborator: Instituto de Salud Carlos III (Funding reference PI18/01861)
Hospital General Universitario Reina Sofía de Murcia
Hospital Universitario Reina Sofia de Cordoba
Hospital General Universitario de Alicante
Hospital Clinic of Barcelona
Hospital Universitario Ramon y Cajal
Hospital General Universitario Santa Lucia
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Hospital Universitario de Guadalajara
Hospital Universitario Virgen de la Arrixaca
Hospital Parc Taulí, Sabadell
Hospital Universitario La Fe
Germans Trias i Pujol Hospital
Complejo Hospitalario Universitario de Albacete
Hospital Universitario Fundación Alcorcón
Hospital General Universitario Elche

Source Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
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.

Overall Status Recruiting
Start Date 2019-11-11
Completion Date 2023-06-30
Primary Completion Date 2022-12-31
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Non-AIDS defining cancers incidence through study completion, an average of 1 year
Survival rate through study completion, an average of 1 year
Secondary Outcome
Measure Time Frame
Safety of the screening: adverse events through study completion, an average of 1 year
Cost-efectiveness through study completion, an average of 1 year
Enrollment 4638
Condition
Intervention

Intervention Type: Diagnostic Test

Intervention Name: Digital rectal exam and / or anal cytology (day 1 and after 36 months)

Description: For anal screening in MSM man or woman with abnormal cervical cytology, genital warts or having anal sex (day 1 and after 36 months)

Arm Group Label: Conventional screening

Intervention Type: Diagnostic Test

Intervention Name: Semestral digital rectal exam and / or anal cytology if abnormal → ANOSCOPY with biopsy

Description: For anal screening in MSM man or woman with abnormal cervical cytology, genital warts or having anal sex (semestral)

Arm Group Label: Enhanced screening

Intervention Type: Diagnostic Test

Intervention Name: Cervical cytology and cervical sample for HPV detection (day 1 and after 36 months)

Description: For Cervix Screening in sexually active woman (day 1 and after 36 months)

Arm Group Label: Conventional screening

Intervention Type: Diagnostic Test

Intervention Name: Semestral cervical cytology and cervical sample for HPV detection

Description: For Cervix Screening in sexually active woman (semestral)

Arm Group Label: Enhanced screening

Intervention Type: Diagnostic Test

Intervention Name: Appointment for mammography (day 1 and after 36 months)

Description: For Breast Screening in woman between 50-70 years old (day 1 and after 36 months)

Arm Group Label: Conventional screening

Intervention Type: Diagnostic Test

Intervention Name: Annual appointment for mammography

Description: For Breast Screening in woman between 45-70 years old (annual)

Arm Group Label: Enhanced screening

Intervention Type: Diagnostic Test

Intervention Name: Semestral appointment for liver ultrasound

Description: For Hepatic Screening: Cirrhosis or Chronic HBV, and meet any of the following risk factors: Asian male> 40 years old Asian woman> 50 years old African man or woman HCC family history

Arm Group Label: Conventional screening

Intervention Type: Diagnostic Test

Intervention Name: Semestral appointment for liver ultrasound

Description: Having chronic liver disease with fibrosis ≥ F3 or Presents chronic HBV

Arm Group Label: Enhanced screening

Intervention Type: Diagnostic Test

Intervention Name: Semestral blood collection for alpha-fetoprotein and others hepatic biomarkers determination

Description: Having chronic liver disease with fibrosis ≥ F3 or Presents chronic HBV

Arm Group Label: Enhanced screening

Intervention Type: Diagnostic Test

Intervention Name: Fecal occult blood test (day 1 and after 36 months)

Description: For Colon Screening: Age between 50-70 years old

Arm Group Label: Conventional screening

Intervention Type: Diagnostic Test

Intervention Name: Annual fecal occult blood test

Description: For Colon Screening: Age older than 40 years

Arm Group Label: Enhanced screening

Intervention Type: Diagnostic Test

Intervention Name: Digital rectal exam and PSA determination (day 1 and after 36 months)

Description: For Prostate Screening: Man older than 50 years

Arm Group Label: Conventional screening

Intervention Type: Diagnostic Test

Intervention Name: Annual digital rectal exam and PSA determination

Description: For Prostate Screening: Man older than 50 years

Arm Group Label: Enhanced screening

Intervention Type: Diagnostic Test

Intervention Name: Annual appointment for low dose computed tomography for lung screening

Description: For Lung Screening: should accomplish ALL the following criteria: Age > 40 years Active smoker or former smoker<3 years, with IPY ≥20. IPY: index of packages-year: nº packages that smoke per day x nº years smoking No contraindications for thoracic surgery No lung infection in the last 2 months

Arm Group Label: Enhanced screening

Intervention Type: Diagnostic Test

Intervention Name: Annual general inspection for skin lesions suggestive of malignancy

Description: For Skin Screening: Woman ≥18 years Man ≥40 years

Arm Group Label: Enhanced screening

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

Gender:

All

Gender Based:

Yes

Gender Description:

Both genders should be represented in a real incidence estimation of Spanish population.

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Félix Gutiérrez-Rodero, PhD Principal Investigator Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Overall Contact

Last Name: Sergio Padilla-Urrea, PhD

Phone: +34 966616234

Email: [email protected]

Location
Facility: Status: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Location Countries

Spain

Verification Date

2021-02-01

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

Investigator Full Name: Felix Gutierrez

Investigator Title: Principal Investigator

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Conventional screening

Type: Active Comparator

Description: Standard screening in the participating centers, adjusted to the recommendations of the European AIDS Society (EACS).

Label: Enhanced screening

Type: Experimental

Description: Expanded screening for early detection of lung, liver, anal, cervical, breast, prostate, colorectal and skin cancer.

Acronym IMPACNEO
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Screening

Masking: None (Open Label)

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