Anal CancerPhase 2SSIBLINGNCT07775209
Shortening Radiation Course Duration Using Simultaneous Integrated Boost With Lower Intensity Elective Nodal Dosing and Concurrent Chemotherapy for High-Risk Anal Squamous Cell Carcinoma
A Phase 2 study testing Hypofractionated Radiation Therapy in people with Anal Cancer, run by University of Vermont Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anal Cancer
- What is being tested?
- Hypofractionated Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Aug 2026to Apr 2040
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of Vermont Medical Center
Burlington, Vermont, 05401
About this study
Official title: 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.
Read the 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.
- Conditions
- Anal Cancer
- Being tested
- Hypofractionated Radiation Therapy
- Keywords
- anal squamous cell carcinoma, Hypofractionated Radiation Therapy, Circulating Tumor DNA
- Medical subject headings
- Anus Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypofractionated Radiation TherapyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Hypofractionated Chemoradiation | Experimental | 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. Receives: Radiation: Hypofractionated Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months after start of radiation therapy
Secondary outcomes (16)
Colostomy-Free Survival
Time from completion of treatment to colostomy placement or last follow-up without colostomy.
Measured: 2 years
Disease-Free Survival
Time from study registration to disease progression, recurrence, or death from any cause.
Measured: 2 years
Locoregional Control
Proportion of participants without locoregional disease failure involving the primary tumor or regional lymph node sites.
Measured: 2 years
Local Control Rate
Proportion of participants without local recurrence at the primary tumor site.
Measured: 2 years
Regional Control Rate
Proportion of participants without recurrence in regional lymph node sites.
Measured: 2 years
Elective Regional Control Rate
Proportion of participants without recurrence in electively treated nodal regions.
Measured: 2 years
Distant Metastasis-Free Survival
Time from study registration to development of distant metastatic disease or death.
Measured: 2 years
Overall Survival
Time from study registration to death from any cause.
Measured: 2 years
Treatment Interruption Rate
Proportion of participants experiencing interruption or delay in planned protocol treatment.
Measured: During treatment (approximately 5 weeks)
Treatment-Related Toxicity
Incidence of clinician-reported treatment-related adverse events graded according to CTCAE version 6.0.
Measured: Baseline through 24 months
Patient-Reported Treatment-Related Symptoms
Patient-reported gastrointestinal, genitourinary, skin, and functional symptoms assessed using PRO-CTCAE.
Measured: Baseline through 24 months
Fecal Incontinence Severity Index Score
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.
Measured: Baseline through 24 months
Hazard Ratio for Clinical Recurrence According to HPV ctDNA Detection Status
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.
Measured: Baseline through 24 months
Patient and Caregiver Treatment Experience Assessed Through Qualitative Interviews
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.
Measured: Approximately 3 months after treatment
Fecal Incontinence Quality of Life Scale Domain Scores
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.
Measured: Baseline through 24 months
Baseline HPV ctDNA Levels According to Selected Clinical Features
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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2026
- Study start26 Aug 2026
- Primary completionMay 2039 (estimated)
- Study completionApr 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Vermont Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christopher Anker, University of Vermont Medical Center
- Investigators
- Christopher L Anker, MD, Principal investigator, University of Vermont Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07775209
- Sponsor's protocol ID
- UVMCC2604
- Other IDs
- temp
- Acronym
- SSIBLING
- Status last verified
- Sep 2026
- First submitted
- 2 Aug 2026
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared because no IPD-sharing plan has been established for this small investigator-initiated study. Study findings may be reported in aggregate form.
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07775209
- Acronym / sponsor ID
- SSIBLING / UVMCC2604
- Conditions
- Anal Cancer
- Keywords
- anal squamous cell carcinoma, Hypofractionated Radiation Therapy, Circulating Tumor DNA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of Vermont Medical CenterUniversity, hospital or other
- Study start
- 26 Aug 2026 (actual)
- Primary completion
- May 2039 (estimated)
- Study completion
- Apr 2040 (estimated)
- First posted
- 20 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: Hypofractionated Chemoradiation | Experimental | Radiation: Hypofractionated Radiation TherapyParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hypofractionated Radiation TherapyParticipants 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. | Radiation | Experimental: Hypofractionated Chemoradiation |
Primary outcome
Complete Clinical Response Rate at 6 Months
Time frame: 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.
16 secondary outcomes
Colostomy-Free Survival
Time frame: 2 years
Disease-Free Survival
Time frame: 2 years
Locoregional Control
Time frame: 2 years
Local Control Rate
Time frame: 2 years
Regional Control Rate
Time frame: 2 years
Elective Regional Control Rate
Time frame: 2 years
Distant Metastasis-Free Survival
Time frame: 2 years
Overall Survival
Time frame: 2 years
Treatment Interruption Rate
Time frame: During treatment (approximately 5 weeks)
Treatment-Related Toxicity
Time frame: Baseline through 24 months
Patient-Reported Treatment-Related Symptoms
Time frame: Baseline through 24 months
Fecal Incontinence Severity Index Score
Time frame: Baseline through 24 months
Hazard Ratio for Clinical Recurrence According to HPV ctDNA Detection Status
Time frame: Baseline through 24 months
Patient and Caregiver Treatment Experience Assessed Through Qualitative Interviews
Time frame: Approximately 3 months after treatment
Fecal Incontinence Quality of Life Scale Domain Scores
Time frame: Baseline through 24 months
Baseline HPV ctDNA Levels According to Selected Clinical Features
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be shared because no IPD-sharing plan has been established for this small investigator-initiated study. Study findings may be reported in aggregate form.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christopher L Anker, MD principal investigator
University of Vermont Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hypofractionated Radiation Therapy in people with Anal Cancer, run by University of Vermont Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Clinical Response Rate at 6 Months (time frame: 6 months after start of radiation therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.