Combining chemoradiotherapy with PD-1 blockade for anal canal cancer

A Phase 3, Multicenter, Double-Blind Randomized Study of Mitomycin, 5-Fluorouracil and IMRT Combined With or Without Anti-PD-1 in Patients With Locally Advanced Anal Canal Squamous Carcinoma

This study is testing if adding a new immune therapy called Sintilimab to standard chemotherapy and radiation helps people with advanced anal canal cancer do better than with just the usual treatment.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 102 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, Sintilimab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05374252 on ClinicalTrials.gov

What this trial studies

This phase III, multi-center, double-blind randomized controlled trial evaluates the effectiveness and safety of combining mitomycin C/5-Fu chemotherapy and long-course IMRT with the PD-1 antibody Sintilimab in patients with locally advanced anal canal squamous carcinoma. Participants will be divided into two groups: one receiving the traditional chemoradiotherapy along with Sintilimab, and the other receiving the traditional treatment without the antibody. The study aims to determine if the addition of PD-1 blockade improves treatment outcomes compared to standard therapy alone.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with histologically confirmed stage III anal canal squamous carcinoma and no prior treatment history.

Not a fit: Patients with previous anal canal surgery, chemotherapy, or immunotherapy treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance treatment efficacy and improve survival rates for patients with anal canal cancer.

How similar studies have performed: Other studies have shown promising results with PD-1 inhibitors in various cancers, suggesting potential success for this approach in anal canal cancer.

Eligibility criteria

Inclusion Criteria:

1. Histology identified anal canal squamous carcinoma,
2. Aged 18 to 75,
3. Clinical staging III, Eastern Cooperative Oncology Group 0-2 score,
4. The Staging method: All patients undergoing rectal anus palpation, high resolution MRI and chest-abdominal enhanced CT, clinical data should be re-evaluated and inclusive by center evaluation group when there is contradictory staging, distant metastasis were excluded by chest-abdominal enhanced CT and pelvic enhanced MRI,
5. No previous anal canal surgery or anal tumor resection (except for biopsy),
6. No previous chemotherapy or pelvic radiotherapy history,
7. No biopharmaceutical treatment history (such as monoclonal antibody), immunotherapy (such as anti PD-1antibody, anti PD-L1 antibody, anti PD-L2 antibody or anti CTLA-4), or other research drug treatment in the previous 5 years,
8. Adequate bone marrow, liver, and kidney function,
9. Clinical complete response (cCR) (Chest, abdominal and pelvic enhanced CT or pelvic enhanced MRI or PET/CT),
10. Informed consent assigned, Final inclusion criteria,
11. Non-pregnant or breast-feeding women,
12. No other malignant disease within 5 years before diagnosis of anal cancer squamous carcinoma (except endocervical cancer in situ or skin basal cell carcinoma which had been cured); no other malignant disease beside anal cancer squamous carcinoma,
13. No other serious disease leading to shortened survival.

Exclusion Criteria:

1. Diagnosed as stage I-II and well differentiated squamous cell carcinoma,
2. Distant metastasis,
3. Received radiation therapy in abdominal or pelvic regions,
4. Pregnant, lactating woman patient or fertile but lacks adequate contraceptives,
5. Arrhythmia need anti-arrhythmia treatment (except β-blocking agent or Digoxin), symptomatic coronary heart disease or myocardial ischemia (myocardial infarction within 6 months) or congestive heart-failure (CHF) \> New York Heart Association grade II,
6. Severe hypertension not well controlled by drugs,
7. Active phase of chronic hepatitis B or hepatitis C (high copies of virus DNA),
8. Patients with active tuberculosis (TB) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening,
9. Other active clinical severe infection (NCI-CTCAE (version 4.0) ),
10. Dyscrasia, organ dysfunction,
11. Known or suspicious allergy to any research-related drugs,
12. Epilepsy needs treatments (Steroid or anti-epilepsy therapy),
13. Other malignant tumor history within 5 years,
14. Drug abuse and medical, psychological, or social factors that may interfere with patients' participation in the study or affect the evaluation of the study,
15. Patients have any active autoimmune diseases or a history of autoimmune diseases (including but not restricted: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism and decreased thyroid function; patients with vitiligo or with complete remission of asthma in childhood and without any intervention in adulthood may be included; patients with asthma requiring bronchodilators intervention are not included,
16. Any anti-infection vaccine 4 weeks before inclusion,
17. Long-term exposure to immune-suppressor, combination of systemic or topical use of corticosteroids (dose\>10mg/day prednisolone or equivalent hormone),
18. Any unstable state might endanger the patients' safety and compliance,
19. Refuses to sign informed consent.

Where this trial is running

Guangzhou, Guangdong

• The Sixth Affiliated Hospital of Sun Yat-sen University — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Xiang-bo Wan, PhD — Sun Yat-sen University
• Study coordinator: Xiang-bo Wan, PhD

Conditions: Anal Canal Cancer Stage III, Anal Squamous Cell Carcinoma, Anal Canal Cancer, Anal Cancer, Radiochemotherapy, PD-1