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

February 1, 2021 updated by: Felix Gutierrez

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

4638

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Gabriel Estan-Cerezo, PhD
  • Phone Number: +34 966616234
  • Email: estany_gab@gva.es

Study Locations

  • Spain
    • Alicante
      • Elche, Alicante, Spain, 03203
        • Recruiting
        • Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SCREENING
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Conventional screening
Standard screening in the participating centers, adjusted to the recommendations of the European AIDS Society (EACS).
Diagnostic test: Digital rectal exam and / or anal cytology (day 1 and after 36 months)
For anal screening in MSM man or woman with abnormal cervical cytology, genital warts or having anal sex (day 1 and after 36 months)
Diagnostic test: Cervical cytology and cervical sample for HPV detection (day 1 and after 36 months)
For Cervix Screening in sexually active woman (day 1 and after 36 months)
Diagnostic test: Appointment for mammography (day 1 and after 36 months)
For Breast Screening in woman between 50-70 years old (day 1 and after 36 months)
Diagnostic test: Semestral appointment for liver ultrasound

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
Diagnostic test: Semestral appointment for liver ultrasound
Having chronic liver disease with fibrosis ≥ F3 or Presents chronic HBV
Diagnostic test: Fecal occult blood test (day 1 and after 36 months)

For Colon Screening:

Age between 50-70 years old

Diagnostic test: Digital rectal exam and PSA determination (day 1 and after 36 months)

For Prostate Screening:

Man older than 50 years
EXPERIMENTAL: Enhanced screening
Expanded screening for early detection of lung, liver, anal, cervical, breast, prostate, colorectal and skin cancer.
Diagnostic test: Semestral appointment for liver ultrasound

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
Diagnostic test: Semestral appointment for liver ultrasound
Having chronic liver disease with fibrosis ≥ F3 or Presents chronic HBV
Diagnostic test: Semestral digital rectal exam and / or anal cytology if abnormal → ANOSCOPY with biopsy
For anal screening in MSM man or woman with abnormal cervical cytology, genital warts or having anal sex (semestral)
Diagnostic test: Semestral cervical cytology and cervical sample for HPV detection
For Cervix Screening in sexually active woman (semestral)
Diagnostic test: Annual appointment for mammography
For Breast Screening in woman between 45-70 years old (annual)
Diagnostic test: Semestral blood collection for alpha-fetoprotein and others hepatic biomarkers determination
Having chronic liver disease with fibrosis ≥ F3 or Presents chronic HBV
Diagnostic test: Annual fecal occult blood test

For Colon Screening:

Age older than 40 years

Diagnostic test: Annual digital rectal exam and PSA determination

For Prostate Screening:

Man older than 50 years

Diagnostic test: Annual appointment for low dose computed tomography for lung screening

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
Diagnostic test: Annual general inspection for skin lesions suggestive of malignancy

For Skin Screening:

Woman ≥18 years Man ≥40 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Non-AIDS defining cancers incidence
Time Frame: through study completion, an average of 1 year
The incidence of different neoplasms not considered as AIDS defining cancers compared between two arms
through study completion, an average of 1 year
Survival rate
Time Frame: through study completion, an average of 1 year
Comparison in survival terms between conventional and enhanced screening arms
through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of the screening: adverse events
Time Frame: through study completion, an average of 1 year
Analyze the safety of the screening program, analyzing its adverse events, including those unnecessary interventions
through study completion, an average of 1 year
Cost-efectiveness
Time Frame: through study completion, an average of 1 year
Analyze the cost-utility ratio of the extended screening program.
through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Felix Gutierrez

Collaborators

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

Investigators

  • Principal Investigator: Félix Gutiérrez-Rodero, PhD, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 11, 2019

Primary Completion (ANTICIPATED)

December 31, 2022

Study Completion (ANTICIPATED)

June 30, 2023

Study Registration Dates

First Submitted

January 27, 2021

First Submitted That Met QC Criteria

February 1, 2021

First Posted (ACTUAL)

February 3, 2021

Study Record Updates

Last Update Posted (ACTUAL)

February 3, 2021

Last Update Submitted That Met QC Criteria

February 1, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMPACNEO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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