A Phase 2 interventional study of Hypofractionated Radiation Therapy in Anal Cancer, sponsored by University of Vermont Medical Center. Enrolling by invitation at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-15.
Sponsored by University of Vermont Medical Center · Phase 2, Interventional, and Treatment
This phase 2 single-arm study will evaluate whether a shortened course of mildly hypofractionated radiation therapy given with standard concurrent chemotherapy (mitomycin C and capecitabine) can provide acceptable tumor control in patients with high-risk non-metastatic anal squamous cell carcinoma. Standard chemoradiation for anal cancer typically requires approximately 5.5 to 6 weeks of daily radiation, which can create substantial logistical burden for patients and caregivers, particularly those in rural settings.
The investigational approach uses a 23-fraction radiation regimen designed to shorten treatment duration while maintaining biologically equivalent tumor-directed dosing compared with standard treatment. The primary question is whether this shorter chemoradiation regimen can achieve an acceptable 6-month complete clinical response rate while maintaining manageable toxicity.
Standard chemoradiation for high-risk non-metastatic anal squamous cell carcinoma typically requires approximately 27 to 30 fractions of radiation delivered over 5.5 to 6 weeks with concurrent chemotherapy. While effective, this prolonged treatment course creates substantial logistical burden for patients and caregivers, particularly for those living in rural regions with limited access to radiation oncology facilities.
This phase 2, single-arm study evaluates a shortened hypofractionated chemoradiation approach designed to reduce treatment duration while maintaining biologically comparable tumor-directed dosing relative to conventional treatment regimens. The investigational radiation regimen uses a simultaneous integrated boost (SIB) approach delivering 23 fractions over approximately 4.5 weeks, with reduced elective nodal dosing and concurrent standard-of-care chemotherapy consisting of mitomycin C and capecitabine.
The study focuses on patients with high-risk non-metastatic anal squamous cell carcinoma, including larger primary tumors and/or node-positive disease, a population for whom treatment de-escalation strategies are generally not appropriate. The primary objective is to evaluate whether this shortened regimen achieves an acceptable 6-month complete clinical response rate. Secondary objectives include assessment of survival outcomes, disease control, treatment interruptions, clinician- and patient-reported toxicity, quality of life, and treatment burden.
Exploratory correlative analyses will evaluate circulating tumor DNA (ctDNA) collected at protocol-specified time points to assess correlations between circulating biomarkers and clinical outcomes. The study also includes optional qualitative patient and caregiver interviews to better understand treatment experience and logistical burden associated with cancer therapy.
T2 tumor measuring ≥4 cm T3 or T4 disease Any node-positive disease
Exclusion Criteria:
Participants receive mildly hypofractionated radiation therapy delivered in 23 fractions using a simultaneous integrated boost approach with concurrent standard-of-care mitomycin C and capecitabine chemotherapy.
Radiation: Hypofractionated Radiation Therapy
Participants receive mildly hypofractionated radiation therapy delivered in 23 fractions using a simultaneous integrated boost approach, given concurrently with standard-of-care mitomycin C and capecitabine chemotherapy.
Complete Clinical Response Rate at 6 Months
Proportion of participants achieving complete clinical response, defined as absence of tumor and malignant ulceration in the anal canal and perianal skin on digital rectal examination and/or anoscopy, with resolution of palpable inguinal lymphadenopathy if present at baseline. Biopsy may be used when clinically indicated to confirm persistent disease.
Time frame: 6 months after start of radiation therapy
Colostomy-Free Survival
Time from completion of treatment to colostomy placement or last follow-up without colostomy.
Time frame: 2 years
Disease-Free Survival
Time from study registration to disease progression, recurrence, or death from any cause.
Time frame: 2 years
Locoregional Control
Proportion of participants without locoregional disease failure involving the primary tumor or regional lymph node sites.
Time frame: 2 years
Local Control Rate
Proportion of participants without local recurrence at the primary tumor site.
Time frame: 2 years
Regional Control Rate
Proportion of participants without recurrence in regional lymph node sites.
Time frame: 2 years
Elective Regional Control Rate
Proportion of participants without recurrence in electively treated nodal regions.
Time frame: 2 years
Distant Metastasis-Free Survival
Time from study registration to development of distant metastatic disease or death.
Time frame: 2 years
Overall Survival
Time from study registration to death from any cause.
Time frame: 2 years
Treatment Interruption Rate
Proportion of participants experiencing interruption or delay in planned protocol treatment.
Time frame: During treatment (approximately 5 weeks)
Treatment-Related Toxicity
Incidence of clinician-reported treatment-related adverse events graded according to CTCAE version 6.0.
Time frame: Baseline through 24 months
Patient-Reported Treatment-Related Symptoms
Patient-reported gastrointestinal, genitourinary, skin, and functional symptoms assessed using PRO-CTCAE.
Time frame: Baseline through 24 months
Fecal Incontinence Severity Index Score
The Fecal Incontinence Severity Index is a patient-reported measure of fecal incontinence severity based on the frequency of accidental leakage of gas, mucus, liquid stool, and solid stool. Total scores range from 0 to 61, with higher scores indicating more severe fecal incontinence.
Time frame: Baseline through 24 months
Hazard Ratio for Clinical Recurrence According to HPV ctDNA Detection Status
HPV ctDNA will be measured in serial plasma samples using a laboratory-based HPV ctDNA assay and categorized as detectable or undetectable. We will assess the correlation between baseline HPV ctDNA levels and selected clinical features via a Wilcoxon test. We will test for correlations between HPV ctDNA detection and recurrence-free survival using a landmark Cox proportional hazards model, with recurrence-free survival compared using the log-rank test Clinical recurrence will be based on radiographic imaging, endoscopic assessment, and/or clinical examination, as determined by the evaluating physician. HPV ctDNA detection will not be considered a recurrence event.
Time frame: Baseline through 24 months
Patient and Caregiver Treatment Experience Assessed Through Qualitative Interviews
Patient and caregiver experiences will be assessed using semi-structured Patient and Caregiver/Support Person Experience Interviews. Interview responses will be reviewed to identify common themes related to treatment burden, convenience, travel requirements, caregiver impact, treatment tolerance, and perceptions of the shortened treatment course.
Time frame: Approximately 3 months after treatment
Fecal Incontinence Quality of Life Scale Domain Scores
The Fecal Incontinence Quality of Life Scale measures quality of life across four domains: lifestyle, coping/behavior, depression/self-perception, and embarrassment. Domain scores range from 1 to 5, with higher scores indicating better quality of life.
Time frame: Baseline through 24 months
Baseline HPV ctDNA Levels According to Selected Clinical Features
Baseline HPV ctDNA levels will be measured in plasma using a laboratory-based HPV ctDNA assay. Correlations between baseline HPV ctDNA levels and selected demographic and disease-related clinical features will be assessed using a Wilcoxon test.
Time frame: Baseline
Plan to share: No — Individual participant data will not be shared because no IPD-sharing plan has been established for this small investigator-initiated study. Study findings may be reported in aggregate form.
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University of Vermont Medical Center