About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants with excision of the primary tumor but with node positive disease or residual disease at the primary if T3-T4N0 will be eligible.

Age ≥18 years

ECOG performance status 0-2

Creatinine clearance >30 ml/min by Cockcroft-Gault Equation.

Disqualifiers

Any prior pelvic radiation or previous radiation that would result in overlapping radiation fields.

History of allergic reactions to compounds similar to capecitabine,

Participants with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen in the opinion of the investigator.

Participants with inflammatory bowel disease, scleroderma, or known homozygosity for DPYD deficiency.

Trial design

Design model

Single group

Treatments tested in this trial

HPV ctDNA Response based radiation
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
Chemotherapy
Drug
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
Retifanlimab
Drug
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.

Treatment groups

33 Participants

are divided into 1 treatment group

Group A: Chemoradiation based on HPV ctDNA responseExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

1-year Disease-free survival (DFS) by response subgroup

DFS is defined the occurrence of progression of local disease, distant metastases, second primary or death. 1-year DFS, will be analyzed using the Kaplan-Meier method and be compared using a 0.05-level one-sided two-proportion test. DFS will be compared among the three subgroups: favorable response subgroup, intermediate response subgroup, unfavorable response subgroup.

Time frame

1 year

Secondary outcomes

1

2-year disease free survival by response subgroup

DFS is defined the occurrence of progression of local disease, distant metastases, second primary or death. 2-year DFS, will be analyzed using the Kaplan-Meier method and be compared using a 0.05-level one-sided two-proportion test. DFS will be compared among the three subgroups: favorable response subgroup, intermediate response subgroup, unfavorable response subgroup.

Time frame

2 years

2

1-year disease control by response subgroup

Disease control is defined as a composite endpoint that includes failure to achieve a clinical response or subsequent disease recurrence. Achieving a clinical response includes the proportion of participants who achieve complete response (CR), partial response (PR), or stable disease (SD) according to Response Evaluation Criteria in Solid Tumors version 1.1. CR is defined as the absence of tumor on re-staging scans and explant or mucosal biopsies (if applicable). PR is defined as a 30% decrease in the sum of diameters of target lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of one or more new lesions. Disease control will be analyzed using the Kaplan-Meier method and be compared using a 0.05-level one-sided two-proportion test.

Time frame

1 year

3

2-year disease control by response subgroup

Disease control is defined as a composite endpoint that includes failure to achieve a clinical response or subsequent disease recurrence. Achieving a clinical response includes the proportion of participants who achieve complete response (CR), partial response (PR), or stable disease (SD) according to Response Evaluation Criteria in Solid Tumors version 1.1. CR is defined as the absence of tumor on re-staging scans and explant or mucosal biopsies (if applicable). PR is defined as a 30% decrease in the sum of diameters of target lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of one or more new lesions. Disease control will be analyzed using the Kaplan-Meier method and be compared using a 0.05-level one-sided two-proportion test.

Time frame

2 years

4

Toxicity Index as assessed by the number of CTCAE events

Events will be graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Time frame

3 months post-treatment (up to 2 years)

ctHPVDNA Response-Adapted Chemoradiation +/- Retifanlimab Treatment in Locally-Advanced Anal Cancer

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts