ANCHOR Study: Anal Cancer/HSIL Outcomes Research Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 4,446
- 试验地点
- 25
- 主要终点
- Anal Cancer Incidence
研究概览
简要总结
The randomized phase of the trial compared topical or ablative treatment with active monitoring in preventing anal cancer in patients with human immunodeficiency virus (HIV) and high-grade squamous intraepithelial lesions (HSIL). Anal HSIL is tissue in the anal canal that has been damaged by infection with human papillomavirus (HPV) and is at risk for turning into anal cancer.
The ANCHOR Data Safety Monitoring Board (DSMB) determined that the primary study endpoint was completed, based on the data and statistical analysis presented to them on 07SEP2021.
In the post-randomization phase of this trial, all enrolled participants are offered treatment for HSIL and/or follow-up, at the participant's choice.
详细描述
PRIMARY OBJECTIVES: The primary objective of this study has been completed for efficacy.
I. To determine the effectiveness of treating anal HSIL to reduce the incidence of anal cancer in human immunodeficiency virus (HIV)-infected men and women.
SECONDARY OBJECTIVES:
I. To determine the safety of infrared coagulation (IRC), electrocautery, imiquimod, laser and 5- fluorouracil treatments for anal HSIL.
II. To assess the responsiveness (sensitivity to change) and clinical significance of the ANCHOR Health-Related Symptom Index (A-HRSI) subscales by comparing change scores within groups of participants as defined by participant responses to the participant global impression of change (PGIC) item. (completed FEB2020)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV positive. Documentation of HIV-1 infection by means of any one of the following: 1) Documentation of HIV diagnosis in the medical record by a licensed health care provider; 2) Documentation of receipt of ART by a licensed health care provider (receipt of at least two agents is required); 3) HIV-1 RNA detection by a licensed HIV-1 RNA assay demonstrating >1000 RNA copies/mL; or, 4) Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid multispot antibody differentiation assay.
- •Biopsy-proven HSIL at baseline
- •At least one focus of HSIL must be identified that is not within a condyloma that may be treated after enrollment into the study
- •For females, documentation that the participant is being followed for cervical cytology (if having a cervix) and/or HPV testing per current ASCCP guidelines, and visual examination of the vulva, vagina, and cervix to rule out cancer/suspicion for cancer within 12 months prior to enrollment
- •Eastern Cooperative Oncology Group (ECOG) performance status <= 1 (Karnofsky >= 70%)
- •Life expectancy of greater than 5 years
- •Absolute neutrophil count: >= 750/mm^3
- •Platelets: >= 75,000/mm^3
- •Hemoglobin >= 9.0 g/dL
- •Women of childbearing potential must have a negative urine pregnancy test within 7 days of initiating study treatment if they have been randomized to the treatment arm; all women of childbearing potential must agree to use a reliable birth control method (oral contraceptive pills, intrauterine device, Nexplanon, DepoProvera, or permanent sterilization, etc., or another acceptable method as determined by the investigator) during the entire period of the trial (5 years or more), and must not intend to become pregnant during study participation and for 3 months after treatment is discontinued; all participants must be willing to comply with an acceptable birth control regimen as determined by the Investigator
- •Men randomized to the treatment arm should not father a baby while receiving topical treatment during this study. Men who could father a child must agree to use at least one form of birth control during or continued abstinence from heterosexual intercourse if receiving topical treatment during the study, and for 2 weeks after stopping topical treatment.
- •Ability to understand and the willingness to sign a written informed consent document
- •Participant is willing to be randomized and able to comply with the protocol
- •Clinician is comfortable with either following patient for up to 5 years without therapy or treating patient for up to 5 years
排除标准
- •Inability to provide informed consent
- •Patients who are receiving any other immunomodulatory investigational agents (replacement doses of steroids for adrenal insufficiency or treatment with prednisone ≤5 mg/day is permitted) within the 4 weeks before randomization enrollment, other than investigational antiretroviral agents for HIV, or investigational or approved agents for Hepatitis C.
- •History of anal cancer, penile, vulvar, vaginal or cervical cancer, or signs of these cancers at baseline.
- •Treatment or removal of HSIL less than 6 months prior to randomization.
- •Participant has symptoms related to HSIL and would benefit more from immediate treatment than from entry into the study and potential for randomization to active monitoring arm
- •Current systemic chemotherapy or radiation therapy that potentially causes bone marrow suppression that would preclude safe treatment of HSIL
- •Participants who only have a single HSIL lesion that is likely to be removed entirely with the initial screening biopsy
- •Warts so extensive that they preclude the clinician from determining the extent and location of HSIL
- •Participant plans to relocate away from the study site to a location without an ANCHOR study site during study participation
研究组 & 干预措施
Arm I (treatment)
Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks, or trichloroacetic acid every 3 weeks up to 12 weeks. Patients receiving ablative treatment using infrared photocoagulation therapy, hyfrecation/electrocautery (thermal ablation therapy), or laser therapy. Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective. The number and timing of such treatments will be at the discretion of the investigator. Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered. All participants will have samples collected for laboratory biomarker analysis.
干预措施: imiquimod (Drug)
Arm I (treatment)
Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks, or trichloroacetic acid every 3 weeks up to 12 weeks. Patients receiving ablative treatment using infrared photocoagulation therapy, hyfrecation/electrocautery (thermal ablation therapy), or laser therapy. Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective. The number and timing of such treatments will be at the discretion of the investigator. Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered. All participants will have samples collected for laboratory biomarker analysis.
干预措施: fluorouracil (Drug)
Arm I (treatment)
Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks, or trichloroacetic acid every 3 weeks up to 12 weeks. Patients receiving ablative treatment using infrared photocoagulation therapy, hyfrecation/electrocautery (thermal ablation therapy), or laser therapy. Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective. The number and timing of such treatments will be at the discretion of the investigator. Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered. All participants will have samples collected for laboratory biomarker analysis.
干预措施: infrared photocoagulation therapy (Device)
Arm I (treatment)
Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks, or trichloroacetic acid every 3 weeks up to 12 weeks. Patients receiving ablative treatment using infrared photocoagulation therapy, hyfrecation/electrocautery (thermal ablation therapy), or laser therapy. Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective. The number and timing of such treatments will be at the discretion of the investigator. Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered. All participants will have samples collected for laboratory biomarker analysis.
干预措施: thermal ablation therapy (Device)
Arm I (treatment)
Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks, or trichloroacetic acid every 3 weeks up to 12 weeks. Patients receiving ablative treatment using infrared photocoagulation therapy, hyfrecation/electrocautery (thermal ablation therapy), or laser therapy. Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective. The number and timing of such treatments will be at the discretion of the investigator. Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered. All participants will have samples collected for laboratory biomarker analysis.
干预措施: laser therapy (Device)
Arm I (treatment)
Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks, or trichloroacetic acid every 3 weeks up to 12 weeks. Patients receiving ablative treatment using infrared photocoagulation therapy, hyfrecation/electrocautery (thermal ablation therapy), or laser therapy. Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective. The number and timing of such treatments will be at the discretion of the investigator. Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered. All participants will have samples collected for laboratory biomarker analysis.
干预措施: clinical observation (Other)
Arm I (treatment)
Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply imiquimod intra-anally, peri-anally or both thrice weekly for up to 16 weeks, fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks, or trichloroacetic acid every 3 weeks up to 12 weeks. Patients receiving ablative treatment using infrared photocoagulation therapy, hyfrecation/electrocautery (thermal ablation therapy), or laser therapy. Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective. The number and timing of such treatments will be at the discretion of the investigator. Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered. All participants will have samples collected for laboratory biomarker analysis.
干预措施: laboratory biomarker analysis (Other)
Arm II (active monitoring) (closed since SEP2021)
Patients undergo active monitoring with examinations for clinical observation every 6 months. Every 12 months, patients undergo biopsies of visible lesions. Patients have cytology sampling performed at every visit. All participants will have samples collected for laboratory biomarker analysis.
干预措施: clinical observation (Other)
Arm II (active monitoring) (closed since SEP2021)
Patients undergo active monitoring with examinations for clinical observation every 6 months. Every 12 months, patients undergo biopsies of visible lesions. Patients have cytology sampling performed at every visit. All participants will have samples collected for laboratory biomarker analysis.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Anal Cancer Incidence
时间窗: Time from randomization to diagnosis of anal cancer, assessed up to 5 years post randomization
Anal cancer incidence is calculated as the number of anal cancer cases detected per 100,000 person years
次要结局
- Incidence of Adverse Events for Each Treatment(Up to 5 years after randomization)
- Change in Physical Symptom Score From Baseline (2-7 Days Post Randomization) Until 4 Weeks Post Randomization(4 weeks post randomization)