Chemoradiotherapy Combined With or Without PD-1 Blockade in Anal Canal Squamous Carcinoma Patients

Sponsor

Sixth Affiliated Hospital, Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05374252

Collaborator

(none)

102

Enrollment

Location

Arms

43.8

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase III, multi-center, double-blind randomized controlled trial assessing the efficacy and safety of concurrent mitomycin C/5-Fu chemotherapy and long-course IMRT combined with PD-1 antibody Sintilimab for locally advanced anal canal squamous carcinoma patients, by comparing an experiment group (traditional chemoradiotherapy with PD-1 antibody Sintilimab) with a control group (traditional treatment without Sintilimab).

Condition or Disease	Intervention/Treatment	Phase
Anal Canal Cancer Stage III Anal Squamous Cell Carcinoma Anal Canal Cancer Anal Cancer	Drug: PD-1 inhibitor Radiation: concurrent chemoradiotherapy	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

102 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 7, 2022

Anticipated Primary Completion Date :

May 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Group Concurrent PD-1 antibody sintilimab combined with mytomicin C, 5-fluorouracil, and IMRT, followed by adjuvant sintilimab	Drug: PD-1 inhibitor Two cycles of concurrent PD-1 antibody sintilimab combined with mytomicin C, 5-fluorouracil and IMRT, followed by adjuvant sintilimab for six months Other Names: radiation concurrent chemotherapy
Active Comparator: Control Group Concurrent mytomicin C and 5-fluorouracil combined with IMRT	Radiation: concurrent chemoradiotherapy Two cycles of concurrent mytomicin C and 5-fluorouracil combined with IMRT Other Names: radiation concurrent chemotherapy

Arm

Intervention/Treatment

Experimental: Experimental Group

Concurrent PD-1 antibody sintilimab combined with mytomicin C, 5-fluorouracil, and IMRT, followed by adjuvant sintilimab

Drug: PD-1 inhibitor

Two cycles of concurrent PD-1 antibody sintilimab combined with mytomicin C, 5-fluorouracil and IMRT, followed by adjuvant sintilimab for six months

Other Names:

radiation

concurrent chemotherapy

Active Comparator: Control Group

Concurrent mytomicin C and 5-fluorouracil combined with IMRT

Radiation: concurrent chemoradiotherapy

Two cycles of concurrent mytomicin C and 5-fluorouracil combined with IMRT

Other Names:

radiation

concurrent chemotherapy

Outcome Measures

Primary Outcome Measures

Progression free survival [from the end of treatment to 3 years after treatment]
progression free survival
Overall survival [from the end of treatment to 3 years after treatment]
overall survival
cCR rate [6 months after treatment]
cCR rate 6 months after treatment

Secondary Outcome Measures

Acute toxicities [from the start of treatment to 3 months after treatment]
acute toxicities according to the NCI CTCAE (version 4.0)
cCR rate [3 months after treatment]
cCR rate 3 months after treatment
The rate of late toxicity according to the RTOG/EORTC scale [3 years]
The rate of late toxicity according to the RTOG/EORTC scale
Colostomy rate [2 year]
colostomy rate
Local recurrence rate [from the end of treatment to 3 years after treatment]
local recurrence rate
Distant metastasis rate [from the end of treatment to 3 years after treatment]
distant metastasis rate
Incidence rate of Grade ≥3 PD-1monoclonal antibody-related adverse events [1 year]
Incidence rate of Grade ≥3 PD-1monoclonal antibody-related adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histology identified anal canal squamous carcinoma,
Aged 18 to 75,
Clinical staging III, Eastern Cooperative Oncology Group 0-2 score,
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,
No previous anal canal surgery or anal tumor resection (except for biopsy),
No previous chemotherapy or pelvic radiotherapy history,
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,
Adequate bone marrow, liver, and kidney function,
Clinical complete response (cCR) (Chest, abdominal and pelvic enhanced CT or pelvic enhanced MRI or PET/CT),
Informed consent assigned, Final inclusion criteria,
Non-pregnant or breast-feeding women,
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,
No other serious disease leading to shortened survival.

Exclusion Criteria:

Diagnosed as stage I-II and well differentiated squamous cell carcinoma,
Distant metastasis,
Received radiation therapy in abdominal or pelvic regions,
Pregnant, lactating woman patient or fertile but lacks adequate contraceptives,
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,
Severe hypertension not well controlled by drugs,
Active phase of chronic hepatitis B or hepatitis C (high copies of virus DNA),
Patients with active tuberculosis (TB) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening,
Other active clinical severe infection (NCI-CTCAE (version 4.0) ),
Dyscrasia, organ dysfunction,
Known or suspicious allergy to any research-related drugs,
Epilepsy needs treatments (Steroid or anti-epilepsy therapy),
Other malignant tumor history within 5 years,
Drug abuse and medical, psychological, or social factors that may interfere with patients' participation in the study or affect the evaluation of the study,
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,
Any anti-infection vaccine 4 weeks before inclusion,
Long-term exposure to immune-suppressor, combination of systemic or topical use of corticosteroids (dose>10mg/day prednisolone or equivalent hormone),
Any unstable state might endanger the patients' safety and compliance,
Refuses to sign informed consent.