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
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Complete Clinical Response Rate at 6 Months
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Experimental: Hypofractionated Chemoradiation
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.
干预措施: Hypofractionated Radiation Therapy (Radiation)
结局指标
主要结局
Complete Clinical Response Rate at 6 Months
时间窗: 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.
次要结局
- Regional Control Rate(2 years)
- Colostomy-Free Survival(2 years)
- Disease-Free Survival(2 years)
- Locoregional Control(2 years)
- Local Control Rate(2 years)
- Elective Regional Control Rate(2 years)
- Distant Metastasis-Free Survival(2 years)
- Overall Survival(2 years)
- Treatment Interruption Rate(During treatment (approximately 5 weeks))
- Treatment-Related Toxicity(Baseline through 24 months)
- Patient-Reported Treatment-Related Symptoms(Baseline through 24 months)
- Fecal Incontinence Severity Index Score(Baseline through 24 months)
- Hazard Ratio for Clinical Recurrence According to HPV ctDNA Detection Status(Baseline through 24 months)
- Patient and Caregiver Treatment Experience Assessed Through Qualitative Interviews(Approximately 3 months after treatment)
- Fecal Incontinence Quality of Life Scale Domain Scores(Baseline through 24 months)
- Baseline HPV ctDNA Levels According to Selected Clinical Features(Baseline)
研究者
Christopher Anker
Radiation Oncologist. Professor, Radiation-Oncology
University of Vermont Medical Center