Shortening Radiation Course Duration Using Simultaneous Integrated Boost With Lower Intensity Elective Nodal Dosing and Concurrent Chemotherapy for High-Risk Anal Squamous Cell Carcinoma (SSIBLING)
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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
-
-
Vermont
-
Burlington, Vermont, Estados Unidos, 05401
- University of Vermont Medical Center
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: 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.
|
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.
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Complete Clinical Response Rate at 6 Months
Prazo: 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.
|
6 months after start of radiation therapy
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Colostomy-Free Survival
Prazo: 2 years
|
Time from completion of treatment to colostomy placement or last follow-up without colostomy.
|
2 years
|
|
Disease-Free Survival
Prazo: 2 years
|
Time from study registration to disease progression, recurrence, or death from any cause.
|
2 years
|
|
Locoregional Control
Prazo: 2 years
|
Proportion of participants without locoregional disease failure involving the primary tumor or regional lymph node sites.
|
2 years
|
|
Local Control Rate
Prazo: 2 years
|
Proportion of participants without local recurrence at the primary tumor site.
|
2 years
|
|
Regional Control Rate
Prazo: 2 years
|
Proportion of participants without recurrence in regional lymph node sites.
|
2 years
|
|
Elective Regional Control Rate
Prazo: 2 years
|
Proportion of participants without recurrence in electively treated nodal regions.
|
2 years
|
|
Distant Metastasis-Free Survival
Prazo: 2 years
|
Time from study registration to development of distant metastatic disease or death.
|
2 years
|
|
Overall Survival
Prazo: 2 years
|
Time from study registration to death from any cause.
|
2 years
|
|
Treatment Interruption Rate
Prazo: During treatment (approximately 5 weeks)
|
Proportion of participants experiencing interruption or delay in planned protocol treatment.
|
During treatment (approximately 5 weeks)
|
|
Treatment-Related Toxicity
Prazo: Baseline through 24 months
|
Incidence of clinician-reported treatment-related adverse events graded according to CTCAE version 6.0.
|
Baseline through 24 months
|
|
Patient-Reported Treatment-Related Symptoms
Prazo: Baseline through 24 months
|
Patient-reported gastrointestinal, genitourinary, skin, and functional symptoms assessed using PRO-CTCAE.
|
Baseline through 24 months
|
|
Fecal Incontinence Severity Index Score
Prazo: 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.
|
Baseline through 24 months
|
|
Hazard Ratio for Clinical Recurrence According to HPV ctDNA Detection Status
Prazo: 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. |
Baseline through 24 months
|
|
Patient and Caregiver Treatment Experience Assessed Through Qualitative Interviews
Prazo: 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.
|
Approximately 3 months after treatment
|
|
Fecal Incontinence Quality of Life Scale Domain Scores
Prazo: 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 through 24 months
|
|
Baseline HPV ctDNA Levels According to Selected Clinical Features
Prazo: 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.
|
Baseline
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Christopher L Anker, MD, University of Vermont Cancer Center
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- UVMCC2604
- temp (Número de outro subsídio/financiamento: University of Vermont Cancer Center)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .