Shortening Radiation Course Duration Using Simultaneous Integrated Boost With Lower Intensity Elective Nodal Dosing and Concurrent Chemotherapy for High-Risk Anal Squamous Cell Carcinoma

Phase 2Enrolling By InvitationNCT07775209

University of Vermont Medical Center24 enrolled

Overview

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Secondary Outcomes

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.