A Phase 3 interventional study of Intensity-Modulated Radiotherapy (IMRT) and Capecitabine in Anal Squamous Cell Carcinoma, Limited-stage, sponsored by Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Recruiting at 2 sites in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-07-09.
Sponsored by Cancer Institute and Hospital, Chinese Academy of Medical Sciences · Phase 3, Interventional, and Treatment
This is a prospective, multicenter, open-label, phase III randomized controlled clinical trial designed to evaluate the efficacy and safety of replacing the traditional chemotherapeutic drug mitomycin with the PD-1 inhibitor sintilimab in definitive chemoradiotherapy for limited-stage anal squamous cell carcinoma. The study plans to enroll 350 previously untreated patients with limited-stage anal squamous cell carcinoma and randomize them in a 1:1 ratio into two groups: the control group will receive the current standard treatment, namely intensity-modulated radiotherapy (IMRT) concurrent with capecitabine and mitomycin; the experimental group will receive an innovative "immunotherapy replacement" regimen, namely IMRT of the same technique concurrent with capecitabine and sintilimab. The study adopts a dual primary endpoint design, aiming to verify that the experimental group is non-inferior to the control group in the clinical complete response rate at 6 months after radiotherapy, and is significantly superior to the control group in the incidence of grade 3 or higher treatment-related acute toxicities.
Exclusion Criteria:
Standard definitive chemoradiotherapy for limited-stage anal squamous cell carcinoma: Intensity-modulated radiotherapy (IMRT) concurrent with capecitabine and mitomycin.
Radiation: Intensity-Modulated Radiotherapy (IMRT) · Drug: Capecitabine · Drug: Mitomycin (MMC)
Innovative immunotherapy replacement regimen: Intensity-modulated radiotherapy (IMRT) concurrent with capecitabine and sintilimab (PD-1 inhibitor) for limited-stage anal squamous cell carcinoma.
Radiation: Intensity-Modulated Radiotherapy (IMRT) · Drug: Capecitabine · Biological: Sintilimab
Intensity-modulated radiotherapy (IMRT) will be administered: * Primary tumor: 1.8 Gy per fraction, 28-30 fractions, total dose 50.4-54 Gy; * Metastatic lymph nodes: 1.68-1.8 Gy per fraction, 30 fractions, total dose 50.4-54 Gy; * Elective nodal regions: 1.5 Gy per fraction, 28-30 fractions, total dose 42-45 Gy; Treatment will be administered 5 days per week, concurrently with systemic chemotherapy (capecitabine ± mitomycin/sintilimab), in accordance with institutional standard practice for anal squamous cell carcinoma.
Oral capecitabine at 825 mg/m² twice daily on days of radiotherapy, concurrent with IMRT, as part of the chemoradiotherapy backbone for both study arms.
Intravenous sintilimab at 200 mg every 3 weeks, administered concurrently with capecitabine and IMRT to the experimental arm as an immunotherapy replacement for mitomycin.
Intravenous mitomycin at 10 mg/m² as a single bolus dose on day 1 of radiotherapy, administered only to the control arm as part of the standard chemoradiotherapy regimen.
Clinical Complete Response (cCR) Rate
cCR is defined as the simultaneous fulfillment of the following criteria: ① Digital rectal examination (DRE): no palpable nodule or ulcer, with only a smooth scar or fibrosis remaining; ② Anoscopy: no macroscopic evidence of residual tumor, with histopathological biopsy required for confirmation if suspicious lesions are present; ③ PET/CT: no residual tumor or new metastatic disease, or no evidence of residual tumor on contrast-enhanced CT or MRI if PET/CT is unavailable.
Time frame: 6 months after radiotherapy
Grade ≥3 acute TRAEs
According to the CTCAE version 5.0 criteria, non-hematologic toxicities of grade ≥3 (including cutaneous and mucosal reactions, gastrointestinal reactions, and genitourinary reactions), hematologic toxicities (including leukopenia, neutropenia, thrombocytopenia, and anemia, excluding lymphopenia), and immune-related adverse events occurring from the start of local treatment to 90 days after the completion of treatment will be evaluated. The investigator will determine whether these events are treatment-related adverse events.
Time frame: From the start of local treatment to 90 days after the completion of treatment
AEs rate
The incidence and severity of all-grade adverse events during treatment and post-treatment will be evaluated according to CTCAE version 5.0, and investigators will determine whether they are immune-related adverse events (irAEs).
Time frame: 2 years after randomization
Quality of life (QoL) in cancer patients
Quality of life in cancer patients will be evaluated using the European Organisation for Treatment and Research of Cancer (EORTC) Quality of Life Questionnaires QLQ-C30. The scoring and interpretation of the QLQ-C30 scales were performed according to the EORTC guidelines. Each item is scored from 0 to 100, with higher scores indicating better functioning on the functional scales/items and more severe symptoms on the symptom scales/items.
Time frame: Baseline, 3 days after completion of radiotherapy, 1 month after radiotherapy, 3 months after radiotherapy, 6 months after radiotherapy, every 3 months up to 2 years after randomization
quality of life (QoL) in anal cancer patients
Anal cancer-specific quality of life will be evaluated using the European Organisation for Treatment and Research of Cancer (EORTC) Quality of Life Questionnaires QLQ-ANL27. The scoring and interpretation of the QLQ-ANL27 scales were performed according to the EORTC guidelines.
Time frame: Baseline, 3 days after completion of radiotherapy, 1 month after radiotherapy, 3 months after radiotherapy, 6 months after radiotherapy, every 3 months up to 2 years after randomization
Anal function
Anal function will be evaluated using the Wexner incontinence score. This scoring system consists of 5 items evaluating the frequency of gas incontinence, frequency of liquid incontinence, frequency of solid incontinence, frequency of wearing pads, and lifestyle alterations, with a score ranging from 0-4 for each question. The total score is calculated, with higher scores indicating poorer anal function.
Time frame: Baseline, 3 days after completion of radiotherapy, 1 month after radiotherapy, 3 months after radiotherapy, 6 months after radiotherapy, every 3 months up to 2 years after randomization
PFS
Progression-free survival (PFS) is defined as the time from enrollment to the first documentation of disease recurrence or progression per RECIST 1.1 criteria, or death from any cause, whichever occurs first. For participants without any event, PFS will be censored at the last follow-up.
Time frame: 2 years after randomization
CFS
Colostomy-free survival (CFS) is defined as the time from enrollment to the first occurrence of permanent colostomy (due to tumor residual/recurrence, severe treatment-related toxicity leading to loss of anal function, or disease progression/recurrence) or death from any cause, whichever occurs first. For participants without any event, CFS will be censored at the last follow-up.
Time frame: 2 years after randomization
LRFS
Locoregional recurrence-free survival (LRFS) is defined as the time from enrollment to the first occurrence of locoregional disease progression (local recurrence or regional lymph node recurrence) or death from any cause, whichever occurs first. For participants without any event, LRFS will be censored at the last follow-up. Local recurrence (LR) is defined as the reappearance of tumor in the anal canal, perianal skin, rectum, or anastomotic site. Persistent disease (tumor that never achieved clinical complete response \[cCR\] after chemoradiotherapy) is considered an event for statistical analysis, but assessment of residual disease within 6 months after radiotherapy completion is not recommended. Regional lymph node recurrence is defined as the reappearance of tumor in regional lymph node drainage areas within the radiation field, including inguinal, mesorectal, presacral, internal iliac, external iliac, and obturator lymph nodes.
Time frame: 2 years after randomization
DMFS
Distant metastasis-free survival (DMFS) is defined as the time from enrollment to the first occurrence of distant metastasis or death from any cause, whichever occurs first. For participants without any event, DMFS will be censored at the last follow-up.
Time frame: 2 years after randomization
OS
Overall survival (OS) is defined as the time from enrollment to death from any cause. For participants without any event, OS will be censored at the last follow-up.
Time frame: 2 years after randomization
Rate of treatment interruption
The proportion of any unplanned radiotherapy interruptions during the scheduled radiotherapy course due to treatment-related adverse events.
Time frame: 2 years after randomization
Plan to share: No
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Cancer Institute and Hospital, Chinese Academy of Medical Sciences