Acceptabilitet og gennemførlighed af kombinationsbehandling for cervikal præcancer blandt sydafrikanske kvinder, der lever med hiv (ACT 2)
30. juli 2026 opdateret af: UNC Lineberger Comprehensive Cancer Center
Formålet med denne undersøgelse er at undersøge, om en anti-cancer medicin (5-fluorouracil creme) placeret i skeden efter en kirurgisk excision procedure er en acceptabel og nyttig form for behandling af cervikal precancer blandt kvinden med HIV-infektion.
Studieoversigt
Status
Afsluttet
Intervention / Behandling
Detaljeret beskrivelse
Der er i øjeblikket ingen medicinske terapier, der anbefales til at fremme clearance af humanpapillom virus (HPV) infektion, regression af cervikal dysplasi eller behandling af cervikal intraepitelial neoplasi (CIN). Human immundefekt virus (HIV)-inficerede kvinder har højere risiko for HPV-infektion, med rater så høje som 45% - 90%. På trods af at de kan forebygges, forekommer cytologiske abnormiteter, cervikal præcancer (højgradig cervikal intraepitelial neoplasi [CIN2/3]) og invasiv livmoderhalskræft også hyppigere hos HIV-inficerede kvinder.
Denne undersøgelse tester, om topisk 5-fluorouracil (5FU) kan bruges som en patientkontrolleret adjuverende behandling af cervikal præcancer (CIN2/3) til selvadministrering efter kirurgisk excision for at reducere risikoen for vedvarende/tilbagevendende CIN2/3 og progression til livmoderhalskræft blandt HIV-smittede kvinder.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
180
Fase
- Ikke anvendelig
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Johannesburg
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Westdene, Johannesburg, Sydafrika, 2092
- Clinical HIV Research Unit Temba Lethu Wing Helen Joseph Hospital
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Beskrivelse
Inklusionskriterier:
- Bekræftet HIV-1 infektion
- På antiretroviral behandling (ART) i mindst 90 dage før indskrivning
- Cervikal biopsi, der viser CIN2/3 inden for de foregående 120 dage.
Ekskluderingskriterier:
- graviditet,
- amning,
- har til hensigt at blive gravid inden for 180 dage efter tilmelding
- har en aktiv seksuelt overført infektion (kvinder kan deltage, når de er blevet behandlet)
- har en kirurgisk fraværende livmoderhals
- har en historie med anogenital (cervikal, vaginal, vulva eller anal) cancer eller en biopsi med mistanke om livmoderhalskræft
- har en medicinsk komorbiditet, der ville forstyrre studiedeltagelsen.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Forebyggelse
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: 5 Fluorouracil (5FU) Cream
Participants self-administered 2 grams intravaginal 5FU cream at study weeks 4, 6, 8, 10, 12, 14, 16, and 18 (8 doses over 16 weeks total).
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Intravaginal topisk kemoterapi, 5-fluorouracil creme
Andre navne:
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Placebo komparator: Placebo Cream
Participants self-administered intravaginal placebo cream (an inert emollient that mimics the 5FU cream) at study weeks 4, 6, 8, 10, 12, 14, 16, and 18 (8 doses over 16 weeks total).
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Intravaginal topisk placebocreme
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Number of Participants Retained in the Study Through Week 24
Tidsramme: Baseline (Week 0) through Week 24
|
Retention was defined as the number of participants who remained in follow-up and completed the Week 24 study visit.
The number and percentage of participants retained at Week 24 were reported for each study arm.
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Baseline (Week 0) through Week 24
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Number of Participants With ≥80% Acceptability Summary Score at Week 10
Tidsramme: Week 10
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Acceptability was defined as a summary score ≥80% on a 7-item questionnaire administered at Week 10.
Each item was rated on a 5-point Likert scale and coded from 0 (lowest acceptability) to 4 (highest acceptability), yielding a total possible score of 0 to 28.
A summary acceptability score was calculated as a percentage (0% to 100%) of the total possible score.
The number and percentage of participants meeting this definition were reported for each study arm.
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Week 10
|
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Number of Participants With ≥80% Acceptability Summary Score by Week 24
Tidsramme: Week 24
|
Acceptability was defined as a summary score ≥80% on the same 7-item questionnaire administered at Week 24.
Each item was rated on a 5-point Likert scale and coded from 0 (lowest acceptability) to 4 (highest acceptability), yielding a total possible score of 0 to 28.
A summary acceptability score was calculated as a percentage (0% to 100%) of the total possible score.
The number and percentage of participants meeting this definition were reported for each study arm.
|
Week 24
|
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Number of Participants Experiencing a Treatment-Related Grade ≥2 Adverse Event or Grade 1 Genital Lesion
Tidsramme: Week 4 (randomization) through Week 24
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A safety event was defined as any Grade 2 or higher adverse event (AE), or any Grade 1 AE involving a genital lesion (blister, ulceration, or pustule), that was assessed as possibly, probably, or definitely related to the study drug.
Adverse events were assessed from Week 4 (randomization) through Week 24.
The number and percentage of participants experiencing at least one such event were reported for each study arm.
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Week 4 (randomization) through Week 24
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Number of Participants Unable or Unwilling to Apply ≥50% of Study Cream Doses Due to Dose-Limiting Toxicity
Tidsramme: Week 4 (randomization) through Week 18
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A tolerability event was defined as inability or unwillingness to apply ≥4 of 8 planned doses of the study treatment due to a dose-limiting toxicity (DLT).
A DLT was defined as (1) any Grade 2 or higher AE, or (2) any Grade 1 AE involving a genital lesion (blister, ulceration, or pustule), that was assessed as possibly, probably, or definitely related to study drug and resulted in an investigator decision to reduce the number of doses or discontinue study treatment.
Tolerability was assessed from randomization through the dosing period (Week 18), with follow-up censored at the last tolerability assessment for participants who exited early without experiencing an event.
The number and percentage of participants experiencing a tolerability event were reported for each study arm.
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Week 4 (randomization) through Week 18
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Number of Participants Adherent to ≥75% of Study Cream Doses Based on Ultraviolet Inspection
Tidsramme: Week 4 (randomization) through Week 24
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Adherence was defined as administration of at ≥6 of 8 planned doses of study treatment, as determined by ultraviolet inspection of returned applicators.
Applicator collection occurred through Week 24, including for participants who completed dosing earlier, to allow complete ascertainment of dose use.
Each applicator was independently assessed by ≥2 reviewers; in cases of disagreement, a third reviewer adjudicated the result.
Participants were classified as adherent if ≥6 applicators showed evidence of use.
Participants who did not meet this threshold, including those with missing or incomplete applicator data, were classified as non-adherent.
The number and percentage of participants meeting this definition were reported for each study arm.
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Week 4 (randomization) through Week 24
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Percent of Participants With CIN2/3 at Baseline Who Regressed to CIN1 or Normal Histology at Week 24
Tidsramme: Baseline (Week 0) through Week 24
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The analysis population included all randomized participants, all of whom had CIN2 or CIN3 at baseline (Week 0) confirmed by loop electrosurgical excision procedure (LEEP) histology.
The analysis population was restricted to participants who completed the Week 24 visit and had cervical biopsy results available.
This included 89 participants in the placebo arm and 81 participants in the 5FU arm.
Regression was defined as improvement from CIN2 or CIN3 at baseline to CIN1 or normal histology at Week 24, as assessed by cervical biopsy.
Participants missing Week 24 data were not included and not considered to have experienced CIN2/3 regression.
The number and percentage of participants meeting this definition were reported for each study arm.
The Wilson score method was used to estimate 95% confidence intervals around percentages.
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Baseline (Week 0) through Week 24
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Percent of Participants With Baseline High-Risk HPV Who Achieved Genotype-Specific Clearance at Week 24
Tidsramme: Baseline (Week 0) through Week 24
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The analysis population was restricted to participants with at least one high-risk HPV (hrHPV) genotype detected at baseline and with hrHPV results available at Week 24.
A total of 69 participants in the 5FU arm and 80 participants in the placebo arm met these criteria.
High-risk HPV clearance was defined as absence at Week 24 of all hrHPV genotypes detected at baseline.
Participants without baseline hrHPV infection or without Week 24 hrHPV results were excluded from this analysis.
The number and percentage of participants meeting this definition were reported for each study arm.
The Wilson score method was used to estimate 95% confidence intervals around percentages.
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Baseline (Week 0) through Week 24
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Carla Chibwesha, MD, MSc, University of North Carolina, Chapel Hill
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- Chibwesha CJ, Mollan KR, Teodoro NS, Keys JR, Liu C, Mulongo M, Gumede S, Pasipamire T, Faesen M, Rahangdale L. ACT 2 Clinical Trial Design: Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among South African Women Living with HIV. medRxiv [Preprint]. 2025 Aug 14:2025.08.12.25333540. doi: 10.1101/2025.08.12.25333540.
- Teodoro NS, Mollan KR, Keys JR, Liu C, Mulongo M, Gumede S, Pasipamire T, Faesen M, Mischell MA, Rahangdale L, Chibwesha CJ. Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among Women Living with HIV in South Africa: Primary Outcomes from the ACT 2 Randomized Trial. medRxiv [Preprint]. 2026 Mar 16:2026.03.14.26348308. doi: 10.64898/2026.03.14.26348308.
- Chibwesha CJ, Teodoro NS, Mollan KR, Keys JR, Liu C, Mulongo M, Gumede S, Pasipamire T, Faesen M, Rahangdale L. Efficacy of Combination Treatment for Cervical Precancer Among Women Living with HIV in South Africa: Secondary Outcomes from the ACT 2 Randomized Controlled Trial. medRxiv [Preprint]. 2026 Mar 22:2026.03.19.26348810. doi: 10.64898/2026.03.19.26348810.
- Chibwesha CJ, Mollan KR, Teodoro NS, Keys JR, Liu C, Mulongo M, Gumede S, Pasipamire T, Faesen M, Rahangdale L. Randomized clinical trial protocol: Acceptability and feasibility of combination treatment for cervical precancer among South African women living with HIV (ACT 2). Contemp Clin Trials. 2026 May;164:108272. doi: 10.1016/j.cct.2026.108272. Epub 2026 Mar 2.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
22. marts 2023
Primær færdiggørelse (Faktiske)
30. juni 2025
Studieafslutning (Faktiske)
30. juni 2025
Datoer for studieregistrering
Først indsendt
7. juni 2022
Først indsendt, der opfyldte QC-kriterier
7. juni 2022
Først opslået (Faktiske)
10. juni 2022
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
21. august 2026
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
30. juli 2026
Sidst verificeret
1. juli 2026
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Blodbårne infektioner
- Urogenitale sygdomme
- Genitale sygdomme
- Urogenitale neoplasmer
- Neoplasmer efter sted
- Neoplasmer
- Urogenitale sygdomme hos kvinder
- Kvinders urogenitale sygdomme og graviditetskomplikationer
- Sygdomme i immunsystemet
- Infektioner
- RNA-virusinfektioner
- Virussygdomme
- Livmodersygdomme
- Kønssygdomme, kvindelige
- Overførbare sygdomme
- Seksuelt overførte sygdomme, virale
- Seksuelt overførte sygdomme
- Lentivirus infektioner
- Retroviridae infektioner
- Immunologiske mangelsyndromer
- Genitale neoplasmer, kvindelige
- Langsomme virussygdomme
- Livmoderhalssygdomme
- Uterine neoplasmer
- HIV-infektioner
- Erhvervet immundefektsyndrom
- Uterine cervikale neoplasmer
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Pyrimidiner
- Uracil
- Pyrimidinoner
- Fluorouracil
Andre undersøgelses-id-numre
- IGHID12046
- 1R01CA250850-01 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
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Al datadeling vil overholde regler og/eller politikker, der er defineret af sponsoren, relevante IRB'er, lokale, statslige og føderale love og regler i USA samt sydafrikanske love og regler.
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