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

Cancer Clinical Trial

— IMPACNEO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04735445
• Other study ID #: IMPACNEO
• Status: Recruiting
• Phase: N/A
• Start date: November 11, 2019
• Est. completion date: June 30, 2023

Study information

• Verified date: February 2021
• Source: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
• Contact: Sergio Padilla-Urrea, PhD
• Phone: +34 966616234
• Email: padilla_ser[@]gva.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4638
• Est. completion date: June 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer
• HIV/AIDS
• Neoplasms

Intervention

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)
• 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)
• 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)
• Semestral cervical cytology and cervical sample for HPV detection
For Cervix Screening in sexually active woman (semestral)
• 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)
• Annual appointment for mammography
For Breast Screening in woman between 45-70 years old (annual)
• 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
• Semestral appointment for liver ultrasound
Having chronic liver disease with fibrosis = F3 or Presents chronic HBV
• Semestral blood collection for alpha-fetoprotein and others hepatic biomarkers determination
Having chronic liver disease with fibrosis = F3 or Presents chronic HBV
• Fecal occult blood test (day 1 and after 36 months)
For Colon Screening: Age between 50-70 years old
• Annual fecal occult blood test
For Colon Screening: Age older than 40 years
• Digital rectal exam and PSA determination (day 1 and after 36 months)
For Prostate Screening: Man older than 50 years
• Annual digital rectal exam and PSA determination
For Prostate Screening: Man older than 50 years
• 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
• Annual general inspection for skin lesions suggestive of malignancy
For Skin Screening: Woman =18 years Man =40 years

Locations

Country	Name	City	State
Spain	Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana	Elche	Alicante

Sponsors (17)

Lead Sponsor

Collaborator

Felix Gutierrez

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

Country where clinical trial is conducted

Spain, 

References & Publications (17)

Althoff KN, McGinnis KA, Wyatt CM, Freiberg MS, Gilbert C, Oursler KK, Rimland D, Rodriguez-Barradas MC, Dubrow R, Park LS, Skanderson M, Shiels MS, Gange SJ, Gebo KA, Justice AC; Veterans Aging Cohort Study (VACS). Comparison of risk and age at diagnosis — View Citation

Cobucci RN, Lima PH, de Souza PC, Costa VV, Cornetta Mda C, Fernandes JV, Gonçalves AK. Assessing the impact of HAART on the incidence of defining and non-defining AIDS cancers among patients with HIV/AIDS: a systematic review. J Infect Public Health. 201 — View Citation

Croxford S, Kitching A, Desai S, Kall M, Edelstein M, Skingsley A, Burns F, Copas A, Brown AE, Sullivan AK, Delpech V. Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general — View Citation

García-Abellán J, Del Río L, García JA, Padilla S, Vivancos MJ, Del Romero J, Asensi V, Hernando A, García-Fraile L, Masiá M, Gutiérrez F; la Cohorte de la Red Nacional de Sida (CoRIS). Risk of cancer in HIV-infected patients in Spain, 2004-2015. The CoRI — View Citation

GBD 2015 HIV Collaborators. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015: the Global Burden of Disease Study 2015. Lancet HIV. 2016 Aug;3(8):e361-e387. doi: 10.1016/S2352-3018(16)30087-X. Epub 2016 Jul — View Citation

Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007 Jul 7;370(9581):59-67. Review. — View Citation

López C, Masiá M, Padilla S, Aquilino A, Bas C, Gutiérrez F. [Deaths due to non-AIDS diseases among HIV infected patients: A 14-year study (1998-2011)]. Enferm Infecc Microbiol Clin. 2016 Apr;34(4):222-7. doi: 10.1016/j.eimc.2015.04.010. Epub 2015 Jun 18. — View Citation

Masiá M, Padilla S, Álvarez D, López JC, Santos I, Soriano V, Hernández-Quero J, Santos J, Tural C, del Amo J, Gutiérrez F; CoRIS. Risk, predictors, and mortality associated with non-AIDS events in newly diagnosed HIV-infected patients: role of antiretrov — View Citation

Patel P, Hanson DL, Sullivan PS, Novak RM, Moorman AC, Tong TC, Holmberg SD, Brooks JT; Adult and Adolescent Spectrum of Disease Project and HIV Outpatient Study Investigators. Incidence of types of cancer among HIV-infected persons compared with the gene — View Citation

Rubinstein PG, Aboulafia DM, Zloza A. Malignancies in HIV/AIDS: from epidemiology to therapeutic challenges. AIDS. 2014 Feb 20;28(4):453-65. doi: 10.1097/QAD.0000000000000071. Review. — View Citation

Ryom L, Cotter A, De Miguel R, Béguelin C, Podlekareva D, Arribas JR, Marzolini C, Mallon P, Rauch A, Kirk O, Molina JM, Guaraldi G, Winston A, Bhagani S, Cinque P, Kowalska JD, Collins S, Battegay M; EACS Governing Board. 2019 update of the European AIDS — View Citation

Santos J, Valencia E; Panel de Expertos de GeSIDA. [Consensus statement on the clinical management of non-AIDS defining malignancies. GeSIDA expert panel]. Enferm Infecc Microbiol Clin. 2014 Oct;32(8):515-22. doi: 10.1016/j.eimc.2014.04.008. Epub 2014 Jun — View Citation

Shiels MS, Cole SR, Kirk GD, Poole C. A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals. J Acquir Immune Defic Syndr. 2009 Dec;52(5):611-22. doi: 10.1097/QAI.0b013e3181b327ca. — View Citation

Shiels MS, Engels EA. Evolving epidemiology of HIV-associated malignancies. Curr Opin HIV AIDS. 2017 Jan;12(1):6-11. Review. — View Citation

Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, Kowalska JD, de Wit S, Law M, el Sadr W, Kirk O, Friis-Moller N, Monforte Ad, Phillips AN, Sabin CA, Lundgren JD; D:A:D Study Group. Trends in underlying causes of death in people with HIV from 1999 — View Citation

Trickey A, May MT, Gill MJ, Grabar S, Vehreschild J, Wit FWNM, Bonnet F, Cavassini M, Abgrall S, Berenguer J, Wyen C, Reiss P, Grabmeier-Pfistershammer K, Guest JL, Shepherd L, Teira R, d'Arminio Monforte A, Del Amo J, Justice A, Costagliola D, Sterne JAC — View Citation

Wang YH, Shen XD. Human immunodeficiency virus infection and mortality risk among lung cancer patients: A systematic review and meta-analysis. Medicine (Baltimore). 2018 Apr;97(15):e0361. doi: 10.1097/MD.0000000000010361. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-AIDS defining cancers incidence	The incidence of different neoplasms not considered as AIDS defining cancers compared between two arms	through study completion, an average of 1 year
Primary	Survival rate	Comparison in survival terms between conventional and enhanced screening arms	through study completion, an average of 1 year
Secondary	Safety of the screening: adverse events	Analyze the safety of the screening program, analyzing its adverse events, including those unnecessary interventions	through study completion, an average of 1 year
Secondary	Cost-efectiveness	Analyze the cost-utility ratio of the extended screening program.	through study completion, an average of 1 year