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| ID | Type | Description | Link |
|---|---|---|---|
| SMPH/SURGERY/COLON RECT | Other Identifier | UW Madison | |
| Protocol Version 2/24/2026 | Other Identifier | UW Madison | |
| 2022-0468 [former] | Other Identifier | UW Madison | |
| UW22123 | Other Identifier | UWCCC ID |
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| Name | Class |
|---|---|
| Wisconsin Partnership Program | OTHER |
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This study is being done to assess the safety of lopinavir/ritonavir in patients with PLWH with AIN. 30 participants will be recruited and can expect to be on active study for approximately 3 months and long term follow up for 40 weeks.
This is a Phase I modified 3 + 3 design, in which the maximum tolerated dose (MTD) will be identified. The 3 + 3 dose escalation will consist of 6 dose levels (18 participants; planned escalation described in arms below) in combination with variation in dosing schedules of the drug lopinavir/ritonavir. This design also allows for some possible intermediate doses to be examined if dose-limiting toxicities (DLTs) occur and de-escalation is needed.
An expansion cohort of 12 participants will occur at the MTD. Once the MTD is determined, then secondary outcomes will be evaluated.
Primary Objective
Secondary Objectives
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Lopinavir/Ritonavir 200mg/50mg (2 cycles) | Experimental | Cohort 1 will receive two 5-day cycles of the low dose of the suppository (Lopinavir/Ritonavir (200mg/50mg)) in Weeks 0 and 2 |
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| Cohort 1b: Lopinavir/Ritonavir 200mg/50mg (3 cycles) | Experimental | Cohort 1b will receive three 5-day cycles of the low dose of the suppository (Lopinavir/Ritonavir (200mg/50mg)) in Weeks 0, 2, and 4 if Cohort 2 has one dose-limiting toxicity (DLT). |
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| Cohort 2: Lopinavir/Ritonavir 400mg/100mg (2 cycles) | Experimental | Cohort 2 will receive two 5-day cycles of the higher dose of the suppository (Lopinavir/Ritonavir (400mg/100mg)) in Weeks 0 and 2, if Cohort 1 dose is safe. |
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| Cohort 2b: Lopinavir/Ritonavir 400mg/100mg (3 cycles) | Experimental | Cohort 2b will receive three 5-day cycle of the higher dose of the suppository (Lopinavir/Ritonavir (400mg/100mg)) in Weeks 0, 2 and 4 if Cohort 3 has one DLT. |
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| Cohort 3: Lopinavir/Ritonavir 600mg/150mg (2 cycles) | Experimental | Cohort 3 will receive two 5-day cycles of the highest dose of the suppository (Lopinavir/Ritonavir (600mg/150mg)) in Weeks 0 and 2, if the Cohort 2 dose is safe. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lopinavir / Ritonavir | Drug | Human Immunodeficiency Virus (HIV) antiviral, given via suppository |
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| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) as determined by the number of participants at each dose level in the escalation cohorts who experienced a dose-limiting toxicity (DLT) | The MTD is the highest explored dose of lopinavir/ritonavir is the dose at which less than 33% of patients experienced a DLT. A DLT is defined as any toxicity at least possibly related to ritonavir/lopinavir with a drug-related Grade greater than or equal to 3. | up to 5 weeks |
| Rate of Grade 3 or above Toxicities in any Organ System in the Escalation Cohorts | Grade 3 or above as delineated in Common Terminology Criteria for Adverse Events v 5.0 (CTCAE) | up to 5 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants in the Expansion Cohort Who Experience Regression of AIN2/3 Determined by Pathology | Efficacy of intra-anal topical lopinavir/ritonavir administration determined by pathology, based on the regression of AIN2/3 at study weeks 16, 28, and 40. Regression defined as either AIN1 or no AIN lesion detected by High resolution anoscopy (HRA)/biopsy and anal cytology. Down grade of disease from AIN2/3 to AIN1 or normal. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Cancer Connect, MD, FACS | Contact | 800-622-8922 | clinicaltrials@cancer.wisc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Evie Carchman, MD, FACS | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UW Digestive Health Center Anoscopy Clinic | Recruiting | Madison | Wisconsin | 53705 | United States |
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| ID | Term |
|---|---|
| D061466 | Lopinavir |
| ID | Term |
|---|---|
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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modified 3+3 design with increasing concentrations of study drug and thorough assessment of potential toxicities.
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| Cohort 4: Lopinavir/Ritonavir 600mg/150mg (3 cycles) | Experimental | Cohort 4 will receive three 5-day cycles of the highest dose of the suppository (Lopinavir/Ritonavir (600mg/150mg)) in Weeks 0, 2, and 4, if the Cohort 3 dose is safe. |
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| week 12, week 40 |
| Number of Participants in the Expansion Cohort Determined clear of HPV by PCR test | HPV clearance determined by quantitative polymerase chain reaction (PCR) test. | week 12, week 40 |
| Number of Tissue Samples with evidence of apoptosis measured by presence of Activated Caspase 3 | Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with activated caspase 3 indicate evidence of apoptosis. | week 12, week 40 |
| Number of Tissue Samples with evidence of autophagy measured by presence of LC3β and p62 | Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with LC3β and p62 indicate evidence of autophagy. | week 12, week 40 |
| Number of Tissue Samples with evidence of cellular proliferation measured by presence of Ki-67 | Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with Ki-67 indicate evidence of cellular proliferation. | week 12, week 40 |
| Number of Tissue Samples with evidence of HPV positivity measured by presence of p16 | Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with p16 indicate evidence of HPV positivity. | week 12, week 40 |
| Number of Tissue Samples with p53 expression | Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). | week 12, week 40 |