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

Shortening Radiation Course Duration Via Simultaneous Integrated Boost With Lower Intensity Elective Nodal Dosing While Giving Concurrent Chemotherapy for High-risk Anal Squamous Cell Carcinoma - a Phase 2 Study

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.

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