Neoadjuvant PD-1 Blockade in Resectable Oral Squamous Cell Carcinoma (NEOPBOSCC)

• ClinicalTrials.gov Identifier: NCT04649476
• Recruitment Status: Active, not recruiting
• First Posted: December 2, 2020
• Last Update Posted: August 19, 2022
• Sponsor: Hospital of Stomatology, Wuhan University
• Collaborator: Jiangsu HengRui Medicine Co., Ltd.
• Information provided by (Responsible Party): Gang Chen, Hospital of Stomatology, Wuhan University

Study Description

Brief Summary:

The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced oral squamous cell carcinoma.

Condition or disease	Intervention/treatment	Phase
Oral Squamous Cell Carcinoma	Drug: Camrelizumab; Drug: Camrelizumanb plus TPF	Phase 2

Detailed Description:

The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced OSCC. And on this basis, we 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study of Neoadjuvant PD-1 Blockade Alone or Plus TPF Induction Chemotherapy for Resectable Local Advanced Oral Squamous Cell Carcinoma
• Actual Study Start Date: March 22, 2021
• Actual Primary Completion Date: August 10, 2022
• Estimated Study Completion Date: August 10, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Neoadjuvant PD-1 blockade alone; The participants will receive 3 doses of neoadjuvant PD-1 blockade. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.	Drug: Camrelizumab; The participants will receive camrelizumab (200 mg) intravenous infusion each 2-week cycle for 3 cycles prior to surgery.; Other Name: SHR-1210
Experimental: Neoadjuvant PD-1 blockade plus TPF induction chemotherapy; The participants will receive 3 doses of PD-1 blockade and 2 courses of TPF induction chemotherapy. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.	Drug: Camrelizumanb plus TPF; 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, 5-Fluorouracil (F) 750 mg/m2 through intravenous infusion each 3-week cycle for 2 cycles.; Other Name: Docetaxel, Cisplatin, 5-Fluorouracil

Outcome Measures

Primary Outcome Measures :

1. Pathologic response. [ Time Frame: 8 weeks. ]
   Pathologic response of resected tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy. The rate of major pathologic response, defined as <10% residual viable tumor cells in the resected specimen.

Secondary Outcome Measures :

1. Radiographic response. [ Time Frame: 8 weeks. ]
   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.
2. Event-free survival (EFS) rate on each treatment arm. [ Time Frame: 24 months. ]
   EFS is the time from the date of randomization to the date of first record of disease progression as defined by RECIST 1.1.
3. Overall survival (OS) on each treatment arm. [ Time Frame: 24 months. ]
   OS is the time from randomization to death due to any cause.
4. Adverse events (AEs). [ Time Frame: 24 months. ]
   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.

Other Outcome Measures:

1. Changes in the level of circualting exosomal PD-L1. [ Time Frame: 24 months. ]
   The level of circulating exosomal PD-L1 at serial time points pre- and on-treatment, as detected by enzyme-linked immunosorbent assay (ELISA).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Histologically documented oral squamous cell carcinoma (biopsy required).
2. Local advanced oral squamous cell carcinoma (clinical stage T1-2N1-3M0, T3-4aN0-3M0) 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.

Contacts and Locations

Locations

China, Hubei

Hospital of Stomatology, Wuhan University

Wuhan, Hubei, China, 430079

Sponsors and Collaborators

Hospital of Stomatology, Wuhan University

Jiangsu HengRui Medicine Co., Ltd.

Investigators

• Principal Investigator: Gang Chen, MD; Hospital of Stomatology, Wuhan University

  Study Documents (Full-Text)

Documents provided by Gang Chen, Hospital of Stomatology, Wuhan University:

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] March 25, 2022

More Information

• Responsible Party: Gang Chen, Chief physician, Professor, Hospital of Stomatology, Wuhan University
• ClinicalTrials.gov Identifier: NCT04649476
• Other Study ID Numbers: HStomatologyWuhan
• First Posted: December 2, 2020
• Last Update Posted: August 19, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Gang Chen, Hospital of Stomatology, Wuhan University:

Neoadjuvant; Oral squamous cell carcinoma; PD-1 blockade; Camrelizumab; TPF induction chemotherapy

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site; Cisplatin; Docetaxel; Fluorouracil; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Antimetabolites, Antineoplastic; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs