Neoadjuvant Anti-PD-1 Immunotherapy With Chemotherapy in Resectable Locally Advanced Oral Squamous Cell Carcinoma

Oral Squamous Cell Carcinoma Clinical Trial

— NEOPCOSCC  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05798793
• Other study ID #: WuhanHStomatology
• Status: Recruiting
• Phase: Phase 3
• Start date: November 21, 2023
• Est. completion date: October 1, 2026

Study information

• Verified date: April 2024
• Source: Hospital of Stomatology, Wuhan University
• Contact: Gang Chen, M.D.
• Phone: +86 02787686215
• Email: geraldchan[@]whu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 309
• Est. completion date: October 1, 2026
• Est. primary completion date: July 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Oral Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Camrelizumab plus TP
The participants will receive camrelizumab (200 mg) through intravenous infusion each 2-week cycle, and docetaxel (T) 75 mg/m2, cisplatin (P) 75 mg/m2 through intravenous infusion each 3-week cycle for 2 cycles.
• TP
The participants will receive docetaxel (T) 75 mg/m2, cisplatin (P) 75 mg/m2 through intravenous infusion each 3-week cycle for 2 cycles.

Locations

Country	Name	City	State
China	Xiangya Hospital of Central South University	Changsha	Hunan
China	Peking university Shenzhen hospital	Shenzhen	Guangdong
China	Hospital of Stomatology, Wuhan University	Wuhan	Hubei

Sponsors (2)

Lead Sponsor	Collaborator
Hospital of Stomatology, Wuhan University	Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in the Level of Circualting Exosomal PD-L1.	The level of circulating exosomal PD-L1 at serial time points pre- and on-treatment, as detected by enzyme-linked immunosorbent assay (ELISA).	24 months.
Primary	Event-free Survival (EFS) Rate on Each Treatment Arm.	EFS is the time from the date of randomization to the date of first record of disease progression as defined by RECIST 1.1.	24 months.
Secondary	Overall Survival (OS) on Each Treatment Arm.	OS is the time from randomization to death due to any cause.	24 months.
Secondary	Radiographic Response.	Clinical response of tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy, as evaluated by radiographic examinations and defined by RECIST 1.1.; Clinical response of tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy, as evaluated by radiographic examinations and defined by RECIST 1.1.	8 weeks.
Secondary	Pathologic Response.	Pathologic response of resected tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy. Pathologic response is defined as sum of pathologic complete response and major pathologic response. Pathologic complete response is defined as the absence of viable residual tumor in resected specimen. The rate of major pathologic response, defined as <10% residual viable tumor cells in the resected specimen.	8 weeks.
Secondary	Adverse Events (AEs).	Number of participants experiencing any sign, symptom, disease, or worsening of preexisting conditions temporally associated with the experimental interventions or irrespective of the experimental interventions.	24 months.