HPV ctDNA Response-Adapted Chemoradiation +/- Retifanlimab Treatment in Advanced-Stage Anal Cancer

Summary

This study is for people who have anal cancer and have not yet had treatment. The regular treatment for people who have anal cancer is chemoradiation therapy (CRT). CRT is when chemotherapy and radiation therapy are given at the same time. Studies show that CRT works well to treat anal cancer and prevents many people from needing surgery which may require a colostomy bag. Doctors know that CRT is an effective way to treat anal cancer. But, they are doing studies to find out how much dose of radiation and chemotherapy should be given during the CRT. Higher doses of chemotherapy and radiation could increase the risk of side effects, but lowering the dose of chemoradiation has the risk of not being as effective to treat the cancer. One way to predict whether participants need higher or lower doses of radiation therapy is to do a blood test called ctDNA (circulating tumor DNA) to test for the presence of human papillomavirus (HPV). This test is done at certain times while participants are getting CRT. This has been shown to be a marker for the presence of anal cancer.

In this study, doctors will tailor lower versus higher doses of CRT based on the tumor response that is measured by ctDNA. The purpose of this study is to see if customizing the dose of chemoradiation based on the amount of ctDNA will increase survival in participants with anal cancer and/or decrease the risk of side effects. Some participants in this study whose cancer does not respond as well to the CRT may have the opportunity to receive a drug called Retifanlimab that stimulates the body's immune system. Retifanlimab is approved by the Federal Drug Administration (FDA) for treating anal cancer that is recurrent or metastatic since there is proven benefit in these situations.

Conditions

• Anal Cancer
• HPV-Related Carcinoma
• Squamous Cell Carcinoma of the Anus

Interventions

RADIATION

HPV ctDNA Response based radiation

Total radiation doses per response group: * Favorable response: 5040 cGy in 28 fractions * Intermediate response: 5400 cGy in 30 fractions * Unfavorable response: 6120 cGy in 34 fractions

DRUG

Chemotherapy

1. Mitomycin-C(MMC) 12 mg/m2 on day 1 AND one of the following: 2. Capecitabine 825 mg/m2 twice daily on all days of radiotherapy for all response groups OR 5-Fluorouracil: 1000 mg/m²/day as a continuous infusion for 96 hours on days 1-4 and 29-32

DRUG

Retifanlimab

Only participants who have an unfavorable response to treatment (measured on blood tests at Weeks 4 and 5) will be eligible to receive Retifanlimab. Retifanlimab is a 500 mg infusion administered intravenously (by IV) over 30 minutes and begins two weeks after participants finish chemoradiation therapy (at Weeks 7-9). Retifanlimab will be administered on Day 1 of each cycle (each cycle is 4 weeks) as tolerated for up to 1 year.

Sponsors & Collaborators

• Incyte Corporation

  collaborator INDUSTRY

• Jennifer Dorth

  lead OTHER

Principal Investigators

• Jennifer Dorth, MD, MHSc · Case Comprehensive Cancer Center, University Hospitals

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-03-31

Primary Completion

2029-01-31

Completion

2029-01-31

FDA Drug

Yes

Countries

• United States

Study Locations