Clinical trial NCT05798793: Neoadjuvant Anti-PD-1 Immunotherapy With Chemotherapy in Resectable Locally Advanced Oral Squamous Cell Carcinoma
Official title: A Multi-Center, Randomized Phase III Study of Neoadjuvant Anti-PD-1 Immunotherapy Plus TP Chemotherapy Versus TP Chemotherapy or Up-Front Surgery in Resectable Locally Advanced Oral Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Oral Squamous Cell Carcinoma
Keywords: Neoadjuvant
Oral squamous cell carcinoma
Anti-PD-1 immunotherapy
Camrelizumab
TP chemotherapy
Lead sponsor: Hospital of Stomatology, Wuhan University
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2023-04-05
Enrollment: 309
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the survival benefit of neoadjuvant anti-PD-1 immunotherapy plus TP chemotherapy compared with TP chemotherapy or up-front surgery in resectable locally advanced oral squamous cell carcinoma.

Detailed description: On the basis of preliminary study, this study is to further verify the efficacy and safety of neoadjuvant anti-PD-1 immunotherapy plus chemotherapy. The further purpose of this study is to investigate the survival benefit of neoadjuvant anti-PD-1 immunotherapy plus TP chemotherapy compared with TP chemotherapy or up-front surgery in resectable locally advanced oral squamous cell carcinoma. And on this basis, the investigators will explore the changes of the profiles and functions of immune cells within tumors, lymph nodes and peripheral blood after the experimental interventions, as well as their correlation with the patients' response and prognosis.

Eligibility criteria: Inclusion Criteria:

1. Histologically documented oral squamous cell carcinoma (biopsy required).
2. Local advanced oral squamous cell carcinoma (clinical stage T1-2N1-2M0, T3-4aN0-2M0) with resection option for potential cure, as assessed by a faculty surgeon at Hospital of Stomatology, Wuhan University.
3. Distant metastasis is excluded by chest CT and emission computed tomograph.
4. Adequate organ function as follows: 1) Leukocyte count ≥ 2,000/mm3; 2) Absolute neutrophil count ≥ 1,000/mm3; 3) Platelet count ≥ 100,000/mm3; 4) Hemoglobin ≥ 90 g/L; 5) Serum albumin ≥30 g/L; 6) Total bilirubin ≤ 1.5 × upper limit of normal (ULN); 7) AST (SGOT) and ALT (SGPT) \< 2.5 × ULN; 8) ALP ≤ 2.5 × ULN; 9) Prothrombin time-international normalized ratio ≤ 1.5; 10) Serum creatinine ≤ 1.5 × ULN; 11) INR/PT≤ 1.5; 12) TSH ≤ ULN.
5. ECOG performance status 0-1.
6. Female patient tested HCG negative in serum or urine within 7 days prior to the start of investigational product. Both patient and partner must agree to use contraception prior to study entry and for the duration of study participation and for up to 120 days after the last dose of PD-1 blockade.
7. Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form.

Exclusion Criteria:

1. History of ≥ 3 grade immune related adverse events (irAEs) or have not recovered to ≤ 1 grade irAEs from previous treatment.
2. History of other treatments for cancer, including surgery, chemotherapy, radiotherapy or molecular targeted therapy within past 5 years.
3. Previous therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 or any other antibody targeting T cell co-regulatory pathways.
4. Active autoimmune disease or history of refractory autoimmune disease.
5. Active systemic infection requiring therapy.
6. Patients who are receiving psychotropic drug or alcohol/drug abuse.
7. Subjects with concurrent other active malignancies.
8. HIV or untreated active HBV or HCV infections, or vaccinated (HBV, flu, varicella, etc) within 4 weeks before recruitment.
9. Uncontrollable systemic diseases, including diabetes, hypertension, etc.
10. History of stroke or transient ischemic attack within past 6 months.
11. Distant metastases or inability to resect after physician evaluation.
12. Serious cardiovascular, respiratory, immune system critical disease or other conditions that the researchers thought might increase the subjects' risk.

Primary outcomes:
measure: Event-free Survival (EFS) Rate on Each Treatment Arm.
timeFrame: 24 months.
Secondary outcomes:
measure: Overall Survival (OS) on Each Treatment Arm.
timeFrame: 24 months.
measure: Radiographic Response.
timeFrame: 8 weeks.
measure: Pathologic Response.
timeFrame: 8 weeks.
measure: Adverse Events (AEs).
timeFrame: 24 months.
Other outcomes:
measure: Changes in the Level of Circualting Exosomal PD-L1.
timeFrame: 24 months.
Locations:
city: Shenzhen
country: China
facility: Peking university Shenzhen hospital
state: Guangdong
city: Wuhan
country: China
facility: Hospital of Stomatology, Wuhan University
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
Study officials:
affiliation: Hospital of Stomatology, Wuhan University
name: Gang Chen, M.D.
role: PRINCIPAL_INVESTIGATOR
References: