Clinical trial NCT05877573: Toripalimab Combined With Neoadjuvant Chemoradiotherapy as First-line Treatment for Locally Advanced，High-Risk，MSS Rectal Cancer
Official title: Toripalimab Combined With Neoadjuvant Chemoradiotherapy as First-line Treatment for Locally Advanced，High-Risk，MSS Rectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Locally Advanced
High-Risk
Rectal Cancer
MSS
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Shanghai Junshi Bioscience Co., Ltd.
First posted: 2023-05-26
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single arm, open-label, prospective clinical trial to evaluate the combination of neoadjuvant short-course radiotherapy and toripalimab (PD-1 antibody) for locally advanced rectal cancer (LARC) patients with high risk factors. A total of 53patients will be enrolled in this trial to receive 5\*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody. Then they will receive the TME surgery and another 2 cycles of CAPOX chemotherapy. The primary end point is the rate of pathological complete response (pCR). The long-term prognosis and adverse effects will also be evaluated and analyzed.


Eligibility criteria: Inclusion Criteria:

* Age 18-75 years old, female and male;
* Pathological confirmed MSS or pMMR rectal adenocarcinoma;
* Clinical stage T3-4 (AJCC 8th) and at least with one high risk factor（CRM+ or EMVI+ or lateral lymph nodes+）;
* No previous chemotherapy, radiotherapy, immunotherapy or other anti-tumor treatment;
* Adequate organ function defined at baseline as:

ANC ≥1.5××109/L，PLt ≥100×109 /L，Hb ≥90 g/L，15×109 /L≥WBC≥4×109 /L; TBIL ≤1.5×ULN, ALT ≤1.5ULN, AST ≤1.5ULN, BUN and Cr ≤1.5×ULN or Ccr

* 60ml/min (Cockcroft-Gault formula);INR ≤1.5×ULN or PT ≤1.5×ULN (when patient didn't accept anticoagulant therapy);

  * Women of childbearing age must have taken reliable contraceptive measures or have a pregnancy test (serum or urine) within 7 days prior to enrollment and the results are negative;

Exclusion Criteria:

* Pathological confirmed rectal squamous cell carcinoma;
* History of other uncured malignancies within 5 years;
* Allergic to any component of chemotherapy or immunotherapy;
* History of any active, known, or suspected autoimmune disease, including but not limited to myasthenia gravis,Myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,Inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulation Swollen disease, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis or Glomerulonephritis.
* With congenital or acquired immunodeficiency (such as those with HIV infection), active hepatitis B or hepatitis C;

Primary outcomes:
measure: pCR rate
timeFrame: The TME surgery will be recommended after the neoadjuvant therapy. The pCR rate is evaluated after surgery. Assessed up to 6 months
Secondary outcomes:
measure: 3-year ORR
timeFrame: Assessed up to 3 years
measure: 3-year DCR
timeFrame: Assessed up to 3 years
measure: 3-year OS
timeFrame: Assessed up to 3 years
measure: AE
timeFrame: Assessed up to 3 years
measure: SAE
timeFrame: Assessed up to 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Dehua Wu, MD
role: PRINCIPAL_INVESTIGATOR
References: