Sintilimab Versus Mitomycin in Combination With Capecitabine and IMRT for Limited-stage Anal Squamous Cell Carcinoma

NCT07692152 | Recruiting Phase 3 DMC

• 1 other identifier: NCC6140
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Anal Squamous Cell Carcinoma, Limited-stage

Keywords

anal squamous cell carcinoma; intensity-modulated radiotherapy; immune checkpoint inhibitors; immunotherapy

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  From the start of local treatment to 90 days after the completion of treatment

Secondary Outcomes (10)

• AEs rate

  2 years after randomization

• Quality of life (QoL) in cancer patients

  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

  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

  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

  2 years after randomization

Study Arms (2)

Control Arm: Mitomycin + Capecitabine + IMRT

ACTIVE COMPARATOR

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)

Experimental Arm: Sintilimab + Capecitabine + IMRT

EXPERIMENTAL

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

Interventions

Intensity-Modulated Radiotherapy (IMRT) RADIATION

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.

Control Arm: Mitomycin + Capecitabine + IMRT; Experimental Arm: Sintilimab + Capecitabine + IMRT

Capecitabine DRUG

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.

Control Arm: Mitomycin + Capecitabine + IMRT; Experimental Arm: Sintilimab + Capecitabine + IMRT

Sintilimab BIOLOGICAL

Intravenous sintilimab at 200 mg every 3 weeks, administered concurrently with capecitabine and IMRT to the experimental arm as an immunotherapy replacement for mitomycin.

Experimental Arm: Sintilimab + Capecitabine + IMRT

Mitomycin (MMC) DRUG

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.

Control Arm: Mitomycin + Capecitabine + IMRT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Staged as cT2-T4N0M0 or cTanyN+M0 by imaging (AJCC 9th).
• No prior tumor resection surgery (other than biopsy) or chemotherapy or other anti-tumor therapy.
• Aged 18-75 years old.
• ECOG performance status of 0-1.
• Adequate organ function reserve: white blood cell (WBC) count ≥3 × 10\^9/L, absolute neutrophil count (ANC) ≥1.5 × 10\^9/L, hemoglobin (Hb) level \>90 g/L, platelet (PLT) count \>100 × 10\^9/L; serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels \<2.5 times the upper limit of normal (ULN); serum bilirubin level ≤1.5 × ULN; serum creatinine (Cr) level \<1.5 × ULN; international normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (APTT) ≤1.5 × ULN.
• No known history of allergy to the study drugs.
• No prior radiotherapy to the planned radiation site.
• Non-pregnant and non-lactating women.
• For HIV-positive patients: at the initiation of the study, a stable combined antiretroviral therapy (CART) regimen must be used, with an HIV viral load of \<50 copies/mL or below the limit of detection, and a CD4+ T-cell count \>300/µL. Patients will be closely monitored during the study, and CART management will follow antiviral treatment guideline recommendations.
• Signed informed consent form.

You may not qualify if:

• Perianal Paget's disease.
• Pregnant or lactating women.
• Severe comorbidities or any medical/psychiatric condition deemed unsuitable for participation in this study.
• Patients with prior antitumor immunotherapy (e.g., anti-CTLA-4, anti-PD-1, or anti-PD-L1 monoclonal antibodies, etc.), with the exception of anti-HPV vaccination.
• History of other malignancies diagnosed within the past 3 years, except for curatively treated basal cell carcinoma of the skin and/or completely resected carcinoma in situ of the cervix, breast, or thyroid.
• Requires chronic use of immunosuppressive medications.
• Patients with severe autoimmune diseases, including but not limited to: symptomatic interstitial lung disease, or active infectious/non-infectious pneumonia; active inflammatory bowel disease (including Crohn's disease, ulcerative colitis); rheumatoid arthritis; scleroderma; systemic lupus erythematosus; autoimmune vasculitis; myasthenia gravis; myositis; autoimmune hepatitis; antiphospholipid syndrome; Wegener's granulomatosis; Sjögren's syndrome; Guillain-Barré syndrome; or multiple sclerosis, etc.
• History of organ transplantation or allogeneic stem cell transplantation.
• Patients with laboratory test values not meeting the relevant criteria within 7 days prior to enrollment.
• Patients with significantly impaired cardiac, hepatic, pulmonary, renal, or bone marrow function.
• Patients with severe, uncontrolled medical conditions or infections. Examples include: severe myocardial infarction, heart failure, unstable angina, or unstable arrhythmia within the past 6 months; respiratory failure and chronic obstructive pulmonary disease; active hepatitis B virus (HBV) infection (HBV-DNA ≥2000 U/mL); hepatitis C virus (HCV) infection; active tuberculosis infection, etc.
• Concurrent use of other investigational drugs or participation in other clinical trials.
• Patients who refuse or are unable to sign the informed consent form for participation in the trial.
• Patients with known allergies or contraindications to the investigational anti-tumor drug or any of its excipients.
• Patients deemed by the investigator to be unsuitable for participation in the study and unlikely to comply with the study procedures, restrictions, and requirements.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (2)

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Beijing, Beijing Municipality, 100021, China

RECRUITING

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen

Shenzhen, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Anus Neoplasms

Interventions

Radiotherapy, Intensity-Modulated; Capecitabine; sintilimab; Mitomycin

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jing Jin, MD, PhD

  Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yangmei Zhou, MD, PhD

CONTACT

+86 0755-66618168-51251; szchiec@163.com

Yuan Tang, MD, PhD

CONTACT

+86-15011304945; tangyuan82@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 26, 2026
• First Posted: July 9, 2026
• Study Start: March 17, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: July 9, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)