CASCADE 2002: PROTECT Study, "PRObiotics to TrEat Anal preCancer Trial

NCT06949800 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 25361U54CA242646
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 2

Brief Summary

This study is focused on treatment of anal high-grade squamous intraepithelial lesions (HSIL) in persons with HIV (PWH), with the ultimate goal of applying the approach toward prevention of anal cancer in this population

Conditions

HSIL, High Grade Squamous Intraepithelial Lesion; HPV-Related Squamous Cell Carcinoma; Anal HSIL

Keywords

HIV; Anal intraepithelial neoplasia (AIN) 3; p16+ AIN 2

Outcome Measures

Primary Outcomes (2)

• Proportion of participants with no disease present

  No anal disease defined as complete regression of lesions as determined by examination of biopsies obtained at HRA

  Up to 36 weeks

• Proportion of participants reporting treatment-emergent adverse events

  The frequency of participants reporting adverse events by group will be classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

  Up to 36 weeks

Secondary Outcomes (2)

• Proportion of participants with demonstrated disease regression

  Up to 36 weeks

• Proportion of participants with HPV-negative status

  1 day

Study Arms (2)

Blinded: EXE-346 probiotic

EXPERIMENTAL

Participants will be blinded and stratified on gender and according to hrHPV status (HPV16 present or absent in baseline swab). After confirmation of biopsy-proven HSIL, participants will receive sachets of EXE-346 or placebo, with the contents suspended in water and consumed orally twice per day for 3 months (12 weeks) with follow-up visits at 24 and 36 weeks. Participants will undergo High resolution anoscopy (HRA) as a safety check at Visit 3 (12 weeks) and at Visit 4 (24 weeks) to ensure HRA has not progressed to cancer. Biopsies will only be performed if there is any concern for progression. Participants with active HSIL at week 36 will be treated with non-investigational, standard of care, hyfrecation as soon as possible, but within 8 weeks.

Drug: EXE-346 Probiotic; Procedure: Usual Care High Resolution Anoscopy (HRA)

Blinded: Placebo

PLACEBO COMPARATOR

Participants will be blinded and stratified on gender and according to hrHPV status (HPV16 present or absent in baseline swab). After confirmation of biopsy-proven HSIL, participants will receive sachets of EXE-346 or placebo, with the contents suspended in water and consumed orally twice per day for 3 months (12 weeks) with follow-up visits at 24 and 36 weeks. Participants will undergo High resolution anoscopy (HRA) as a safety check at Visit 3 (12 weeks) and at Visit 4 (24 weeks) to ensure HRA has not progressed to cancer. Biopsies will only be performed if there is any concern for progression. Participants with active HSIL at week 36 will be treated with non-investigational, standard of care, hyfrecation as soon as possible, but within 8 weeks.

Drug: Placebo; Procedure: Usual Care High Resolution Anoscopy (HRA)

Interventions

EXE-346 Probiotic DRUG

Given as a single-dose, powder packet to mix with water

Also known as: EXE-346 Probiotic formula, Probiotic

Blinded: EXE-346 probiotic

Placebo DRUG

Given as a single-dose, powder packet to mix with water

Also known as: Blinded Placebo

Blinded: Placebo

Usual Care High Resolution Anoscopy (HRA) PROCEDURE

Non-investigational HRA will be performed

Also known as: HRA

Blinded: EXE-346 probiotic; Blinded: Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Participant in ULACNet-101 or participant screened specifically for ULACNet-102.
• Biopsy-proven anal HSIL (men or women) shown as part of participation in the ULACNet-101 study or at a screening visit for ULACNet-102.
• At least one focus of anal HSIL must be large enough to be monitored for response, i.e.,not completely removed after the screening biopsy.
• Total volume of HSIL is less than 50% of the anal canal or perianal region.
• Must be actively on treatment with effective antiretroviral therapy (ART) regimen for at least three months preceding enrollment (Visit 1, Day 1) in ULACNet-101 or at screening for ULACNet-102.
• HIV RNA \<200 copies/ml at baseline.
• Cluster of differentiation 4 (CD4) nadir above 200 cells per microliter (uL)
• Eastern Cooperative Oncology Group (ECOG) performance status \<=1 (Karnofsky \>= 70%).
• Participants must meet the following laboratory parameters within 3 months before enrollment:
• Leukocytes: ≥3,000/mm\^3.
• Absolute neutrophil count: ≥1,500/mm\^3.
• Platelets: ≥100,000/mm\^3.
• Elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin \<2 times the upper limit of normal.
• Not pregnant or breast feeding and one of the following:

You may not qualify if:

• History of any anogenital cancer.
• Presence of untreated cervical HSIL or cervical cancer.
• Anal HSIL on clinical examination or biopsy that clinicians are concerned for cancer.
• Receipt of chemotherapy, radiotherapy or immunosuppressive medication in three months preceding enrollment in ULACNet-101 or at the screening visit for ULACNet-102.
• Immunosuppression as a result of underlying illness or treatment including:
• Use of high dose corticosteroids (\>10 mg/day prednisone or equivalent) for \>=7 days (inhaled, otic, topical and ophthalmic corticosteroids are permitted).
• Primary immune deficiency disease.
• Use of synthetic or biologic disease-modifying anti-rheumatic drugs.
• History of bone marrow or solid organ transplant.
• History of any other clinically significant autoimmune or immunosuppressive disease.
• Participant initiated a new treatment with antibiotics within the 2 weeks prior to screening or plans to start antibiotic therapy during the study period.
• Participant is taking NSAIDs as a long-term treatment (ie, consistent use for at least 4 days/week each month). Acute use of NSAIDs is allowed.
• Participant has known hypersensitivity to EXE-346 or any product components.
• Current known infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
• Warts so extensive that they preclude the clinician from determining the extent and location of HSIL.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Exegi Pharma, LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Puerto Rico Comprehensive Cancer Center

San Juan, 00936, Puerto Rico

Location

MeSH Terms

Conditions

Squamous Intraepithelial Lesions

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Joel Palefsky, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ross Jamison

CONTACT

(415) 353-9042; Ross.Jamison@ucsf.edu

Jenn Marino

CONTACT

(415) 5141062; jenn.marino@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2025
• First Posted: April 29, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: For the duration of study activities

Locations

US (1); PR (1)