Chemoradiotherapy and Anti-PD-1 Antibody in Anal Squamous Cell Cancer：Chase (Chase)

Chinese Multicenter Phase II Trial of Chemoradiotherapy and Anti-PD-1 Antibody in Anal Squamous Cell Cancer：Chase

Squamous cell carcinoma (SCC) of the anus is a rare malignancy. For localized anal squamous cell carcinoma , definitive chemoradiotherapy is the standard treatment. Patients who do not achieve complete response （CR）or experience recurrence require radical surgery with permanent colostomy.

In previous studies of anal squamous cell carcinoma （ASCC）, although favorable response rates were achieved after concurrent chemoradiotherapy, high rates of local recurrence and distant metastasis were also observed in patients with locally advanced disease, which adversely affect patient survival.

Clinical studies have demonstrated that single-agent PD-1/PD-L1 inhibitors, including nivolumab and pembrolizumab, show promising efficacy in advanced anal squamous cell carcinoma. Given the high recurrence rate associated with current concurrent chemoradiotherapy regimens and the characteristics of the immune microenvironment in anal cancer, the combination of immunotherapy with concurrent chemoradiotherapy is expected to improve therapeutic outcomes.

Therefore, we designed this prospective, multicenter, phase II clinical study to investigate the efficacy and safety of concurrent chemoradiotherapy combined with immune checkpoint inhibitors in anal cancer. This study aims to enhance the therapeutic effect for patients with locally advanced, recurrent, or metastatic anal squamous cell carcinoma and reduce adverse events in patients with high-risk factors after local excision or in early-stage disease.

The primary endpoints are local tumor control rate, overall survival, and radiation-related toxicity. The results will provide evidence for subsequent randomized controlled trials.

Study Overview

• Status: Recruiting
• Conditions: Anal Squamous Cell Cancer
• Intervention / Treatment: Drug: PD-1 Inhibitor + Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 241
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Zhen Zhang, MD; Phone Number: +86-021-64175590; Email: zhen_zhang@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

This study consists of four cohorts. Inclusion and exclusion criteria comprise general inclusion criteria, cohort-specific inclusion criteria, general exclusion criteria, and cohort-specific exclusion criteria.

General Inclusion Criteria Age 18-75 years, male or female; Pathologically confirmed squamous cell carcinoma of the anal canal or perianal region; ECOG performance status 0-1 and life expectancy ≥ 3 months; Adequate organ function:(1) Absolute neutrophil count ≥ 1.5 ×10⁹/L; platelet count ≥ 100 ×10⁹/L; hemoglobin ≥ 9 g/dL; serum albumin ≥ 3 g/dL;(2) Thyroid-stimulating hormone (TSH) ≤ 1 × upper limit of normal (ULN), with normal T3 and T4;(3) Bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2 × ULN;(4) Serum creatinine ≤ 1.5 × ULN, creatinine clearance ≥ 60 mL/min;(5) International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN, unless the patient is on anticoagulation with PT within the expected therapeutic range; activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN; No severe comorbidities expected to limit survival to < 5 years; Female subjects: negative pregnancy test (if of childbearing potential) or permanently non-childbearing potential; Sexually active males and females of childbearing potential must agree to use effective contraception during the entire study period and for 12 months after completion of study treatment; Written and dated informed consent indicating the patient has been informed of all relevant aspects of the study; No concurrent medical condition requiring mandatory hormone replacement therapy; Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Inclusion Criteria for Cohort 1 In addition to the general inclusion criteria:（1）Tumor < 5 cm (T1-2) and negative regional lymph nodes (N-) on physical examination or contrast-enhanced pelvic MRI;(2) No prior anti-tumor therapy.

Inclusion Criteria for Cohort 2 In addition to the general inclusion criteria:(1) No residual tumor detectable on physical examination or imaging after local excision;(2) No prior anti-tumor therapy including radiotherapy, chemotherapy, targeted therapy, or immunotherapy.

Inclusion Criteria for Cohort 3 In addition to the general inclusion criteria:(1) Tumor ≥ 5 cm (T3), or invasion of adjacent organs (T4), or regional lymph node positivity (N+) in mesorectal, presacral, internal/external iliac, or inguinal lymph node regions on physical examination or contrast-enhanced pelvic MRI;(2) No prior anti-tumor therapy.

Inclusion Criteria for Cohort 4 In addition to the general inclusion criteria:(1) Initial distant metastasis (M1) (liver, lung, bone, distant lymph nodes, etc.) confirmed by chest/abdominal CT or PET-CT,or pelvic recurrence after prior treatment, with or without distant metastasis.

Exclusion Criteria:

Patients with any of the following criteria are ineligible for this study:

Pathological diagnosis of other anal tumors, such as gastrointestinal stromal tumor, lymphoma, melanoma, etc.; Prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies; Previous or concurrent malignancy, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma; Active autoimmune disease or history of autoimmune disease (including but not limited to interstitial lung disease, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism); excluding: autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement therapy; type 1 diabetes mellitus on a stable dose of insulin; vitiligo; childhood asthma/allergy that resolved with no intervention required in adulthood; History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency disorders, history of organ transplantation or allogeneic bone marrow transplantation; History of interstitial lung disease (excluding radiation pneumonitis not requiring corticosteroid therapy) or non-infectious pneumonitis; Active pulmonary tuberculosis confirmed by medical history or CT scan, active tuberculosis within 1 year prior to enrollment, or inactive tuberculosis for more than 1 year without standard anti-tuberculosis treatment; Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL) or active hepatitis C (positive anti-HCV antibody with HCV RNA above the lower limit of detection); Severe cardiac, pulmonary, hepatic, or renal dysfunction; History of psychoactive substance abuse, alcoholism, or drug addiction; Any other conditions judged by the investigator that may compromise patient safety or study compliance, including severe medical or psychiatric disorders requiring concurrent treatment, significant laboratory abnormalities, or other social or family factors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early stage anal squamous cell carcinoma; Tumor size <5 cm (T1-2) and negative regional lymph nodes (N-) demonstrated by physical examination or contrast-enhanced pelvic MRI. After short-course radiotherapy, 4 cycles of albumin-bound paclitaxel plus platinum and sintilimab will be administered.	Drug: PD-1 Inhibitor + Chemotherapy; chemotherapy and sintilimab; Other Names: radiotherapy
Experimental: local resection of anal squamous cell carcinoma; Inclusion criteria：no residual tumor visible on physical examination or imaging after local excision.Pathology after local excision reveals high-risk factors, positive margins, or unknown margins.Following short-course radiotherapy, 4 cycles of albumin-bound paclitaxel plus platinum and sintilimab will be administered.Primary endpoint: Severe acute toxicity.	Drug: PD-1 Inhibitor + Chemotherapy; chemotherapy and sintilimab; Other Names: radiotherapy
Experimental: Locally advanced anal squamous cell carcinoma; Eligibility Criteria:Tumor ≥5 cm (T3) demonstrated by physical examination or contrast-enhanced pelvic MRI;or invasion of adjacent organs (T4);or regional lymph node positivity (N+) in the mesorectal, presacral, internal/external iliac, or inguinal lymph node regions. Treatment:Long-course radiotherapy at 54-56 Gy,concurrent with 2 cycles of albumin-bound paclitaxel plus platinum.After completion of radiotherapy,4 cycles of albumin-bound paclitaxel plus platinum and sintilimab will be administered. Primary Endpoint:Complete response rate (including cCR and pCR).	Drug: PD-1 Inhibitor + Chemotherapy; chemotherapy and sintilimab; Other Names: radiotherapy
Experimental: Recurrent and metastatic anal squamous cell carcinoma; Eligibility Criteria:Initial distant metastasis (M1) in the liver, lung, bone, distant lymph nodes, or other sites confirmed by chest and abdominal CT or PET-CT;or pelvic recurrence after prior treatment, with or without distant metastasis. Treatment:Radiotherapy to recurrent or metastatic lesions, followed by chemotherapy combined with sintilimab. Primary Endpoint:12-month progression-free survival (PFS).	Drug: PD-1 Inhibitor + Chemotherapy; chemotherapy and sintilimab; Other Names: radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate	the primary endpoint of cohort 3 is CR rate including cCR and pCR	1 month after the surgery or the decision of Watch and wait
Severe acute toxicity.	The primary endpoint for Cohort 1 (early anal squamous cell carcinoma) and Cohort 2 (post-local excision anal squamous cell carcinoma) is the rate of severe adverse events.	from the start of radiotherapy to 3 months after the start of radiotherapy
12-month progression-free survival (PFS).	The primary endpoint for Cohort 4 (recurrent or metastetic anal squamous cell carcinoma) is 12-month progression-free survival (PFS).	The proportion of patients who were alive and progression-free from the start of initial treatment up to 12 months.

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 16, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 29, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; chemoradiotherapy; Anal Squamous Cell Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Anus Diseases; Rectal Neoplasms; Anus Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Therapeutics; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Immune Checkpoint Inhibitors; Radiotherapy; Drug Therapy
• Other Study ID Numbers: Chase1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No