Anal Cancer
Conditions
Keywords
anal squamous cell carcinoma, Hypofractionated Radiation Therapy, Circulating Tumor DNA
Brief summary
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.
Detailed description
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.
Interventions
RADIATIONHypofractionated 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.
Sponsors
University of Vermont Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Histologically or cytologically confirmed non-metastatic anal squamous cell carcinoma meeting one of the following criteria: T2 tumor measuring ≥4 cm T3 or T4 disease Any node-positive disease * Patients with HPV-associated (p16-positive) perianal cancer are eligible if the tumor extends to the anal verge * Karnofsky Performance Status \>60 * Creatinine clearance \>30 mL/min * Considered by the investigator to be appropriate candidates for concurrent capecitabine and mitomycin C chemotherapy * Ability to understand and willingness to provide informed consent * For participants of childbearing potential: negative pregnancy test or documented absence of pregnancy per institutional standard within 14 days prior to registration * Participants of reproductive potential must agree to use adequate contraception during study treatment and for 90 days after completion of therapy
Exclusion criteria
* Prior pelvic radiation therapy * Uncontrolled intercurrent illness that, in the opinion of the investigator, would prevent safe receipt of radiation therapy or capecitabine * Prior or concurrent malignancy that, in the opinion of the investigator, could interfere with assessment of safety or efficacy * Current receipt of another investigational agent for treatment of anal squamous cell carcinoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Clinical Response Rate at 6 Months | 6 months after start of radiation therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Colostomy-Free Survival | 2 years | Time from completion of treatment to colostomy placement or last follow-up without colostomy. |
| Disease-Free Survival | 2 years | Time from study registration to disease progression, recurrence, or death from any cause. |
| Locoregional Control | 2 years | Proportion of participants without locoregional disease failure involving the primary tumor or regional lymph node sites. |
| Local Control Rate | 2 years | Proportion of participants without local recurrence at the primary tumor site. |
| Regional Control Rate | 2 years | Proportion of participants without recurrence in regional lymph node sites. |
| Elective Regional Control Rate | 2 years | Proportion of participants without recurrence in electively treated nodal regions. |
| Distant Metastasis-Free Survival | 2 years | Time from study registration to development of distant metastatic disease or death. |
| Overall Survival | 2 years | Time from study registration to death from any cause. |
| Treatment Interruption Rate | During treatment (approximately 5 weeks) | Proportion of participants experiencing interruption or delay in planned protocol treatment. |
| Treatment-Related Toxicity | Baseline through 24 months | Incidence of clinician-reported treatment-related adverse events graded according to CTCAE version 6.0. |
| Patient-Reported Treatment-Related Symptoms | Baseline through 24 months | Patient-reported gastrointestinal, genitourinary, skin, and functional symptoms assessed using PRO-CTCAE. |
| Fecal Incontinence Severity Index Score | Baseline through 24 months | 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. |
| Hazard Ratio for Clinical Recurrence According to HPV ctDNA Detection Status | Baseline through 24 months | 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. |
| Patient and Caregiver Treatment Experience Assessed Through Qualitative Interviews | Approximately 3 months after treatment | 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. |
| Fecal Incontinence Quality of Life Scale Domain Scores | Baseline through 24 months | 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. |
| Baseline HPV ctDNA Levels According to Selected Clinical Features | Baseline | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORChristopher L Anker, MD
University of Vermont Cancer Center
Outcome results
None listed