Neoadjuvant Immunochemotherapy for LAOSCC

Neoadjuvant Immunochemotherapy with Tislelizumab, Albumin Paclitaxel and Cisplatin Followed by Standard Therapy Versus Standard Therapy for Locally Advanced Oral Squamous Cell Carcinoma, a Multicenter Randomized Phase 3 Trial

To evaluate the prognostic efficacy of neoadjuvant immunochemotherapy with tislelizumab, albumin paclitaxel and cisplatin followed by radical surgery and adjuvant therapy compared with standard therapy for patients with locally advanced and resectable oral squamous cell carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Oral Squamous Cell Carcinoma; Locally Advanced Head and Neck Carcinoma
• Intervention / Treatment: Drug: albumin paclitaxel, cispatin, tislelizumab

Detailed Description

Neoadjuvant therapy (NAT) is regarded as an effective way to reduce or downgrade the locally advanced or aggressive cancers, and to improve the chance of eradication of the locoregional lesions by radical surgery and/or radiotherapy. However, there are still debates on the clinical value of NAT for patients with locally advanced oral squamous cell carcinoma (LAOSCC). In a series of clinical trials on neoadjuvant therapy for LAOSCC have been carried out by our research group, the pathological efficacy of neoadjuvant immunochemotherapy is superior to neoadjuvant immunotarget therapy, neoadjuvant chemotarget therapy, or neoadjuvant chemotherapy. And in the neoadjuvant immunochemotherapy clinical trial (NCT04473716), the results of the safety and efficacy of neoadjuvant regimen showed that the neoadjuvant regimen of immunochemotherapy was well tolerated, with an MPR rate of 60% and 2-year OS of 90%, which were better than previously reported patients receiving standard treatment for LAOSCC. However, limited to single-arm clinical trial, the patients with LAOSCC benefit from neoadjuvant immunochemotherapy for survival, randomized controlled trials with larger sample size are needed. The aim of present trial is to evaluate the prognostic efficacy of 2-year survival rate in patients with LAOSCC receiving neoadjuvant immunochemotherapy with tiralizumab, albumin paclitaxel and cisplatin followed by radical surgery and adjuvant therapy compared with standard therapy.

The patients with LAOSCC would receive NAT with tiralizumab, albumin paclitaxel and cisplatin followed by radical surgery and adjuvant therapy (the experimental group) or radical surgery and adjuvant therapy (the control group). A total number of 134 patients will be recruited. Neoadjuvant immunochemotherapy: for the patients who are randomly assigned to the experimental group, the palpable edges of the primary lesion (both the longest and shortest axis) would be marked before NAT by at least four points, which is 0.5cm away; 260mg/m2 albuminpaclitaxel intravenously on day 1 and day 22, with 75mg/m2 of cisplatin at an hour interval and 200mg of tislelizumab at an hour interval will be performed. NAT will be given every 3 weeks for 2 cycles, unless there is disease progression, unacceptable toxic effects, or withdrawal of consent by the patients. Surgery will be performed within 2 weeks after completion of NAT. Surgery: Radical resection of the primary lesion and full neck dissection with proper reconstruction will be performed. The safety margins of the primary lesion are 1.0-1.5cm far away from the palpable margins of the lesion; for patients who received NAT, the safety margins are 1.0cm away from the marks that were placed before NAT, to ensure the same extent surgery in both groups. Post-operative adjuvant therapy: radiotherapy will be arranged 4 to 6 weeks after surgery. Routine external beam radiotherapy, will be performed, and the dose is 1.8-2Gy/day, 5 days/week for 6 weeks, and totally 54-60Gy, in the patient with high risk features, concurrent chemotherapy with cisplatin of 80mg/m2 will be used; in the experimental group, adjuvant maintaining therapy of 200mg of tislelizumab, every 3 weeks, for one year will be used. A complete medical history will be obtained and tumor assessment will be performed at baseline. Clinical tumor response will be assessed by clinical evaluation, imaging evaluation will be characterized according to the criteria of response evaluation criteria in solid tumors (version 1.1) before surgery. Post-operative pathological response will be assessed by post-operative pathological examination. Patients will be followed-up by every three months in the first 2 years, every six months in the next 3-5 years, and once a year thereafter until death or data censoring. Overall survival will be calculated from the date of randomization to the date of death; event free survival will be calculated from the date of randomization to local recurrence, regional recurrence, distant metastasis, disease progress, or death; disease free survival will be calculated from the date of randomization to tumor recurrence or distant metastasis or death from any cause.

• Study Type: Interventional
• Enrollment (Estimated): 134
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lai-ping Zhong, MD, PhD; Phone Number: +862152888915; Email: zhonglp@hotmail.com
• Study Contact Backup: Name: Ying-ying Huang, MD; Phone Number: 7182 +862152889999; Email: kqyxyhyy@163.com

Study Locations

• China
  • Shanghai, China, 200040
    • Recruiting
    • Huashan Hospital, Fudan University
    • Contact: Lai-ping Zhong, MD, PhD; Phone Number: +862152888915; Email: zhonglp@hotmail.com
    • Contact: Ying-ying Huang, MD; Phone Number: 7182 +862152889999; Email: kqyxyhyy@163.com
    • Contact: Jing-song Li, MD, PhD
    • Contact: Xue-kui Liu, MD, PhD
    • Contact: Lei Tao, MD, PhD
    • Contact: Yu Wang, MD, PhD
    • Contact: Can-hua Jiang, MD, PhD
    • Contact: Li-song Lin, MD, PhD
    • Contact: Jian Meng, MD, PhD
    • Contact: Qi Zhu, MD, PhD
    • Contact: Ying-ying Huang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1
2. Histopathological diagnosis of oral squamous cell carcinoma (including tongue, gums, cheek, floor of mouth, hard palate, and posterior molar region)
3. Primary tumor with a clinical stage of III/IVA (T1-2/N1-2/M0 or T3-4a/cN0-2/M0, AJCC 2018)
4. Patients must have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
5. Blood routine: white blood cells (WBCs) >3,000/mm3, hemoglobin >8 g/L, platelets >80,000/mm3
6. Liver function: alanine amino transferase/aspartate amino transferase (ALAT/ASAT) <2.5 times the upper limit of normal and bilirubin <1.5 times the upper limit of normal
7. Renal function: Serum creatinine <1.5 times the upper limit of normal
8. Coagulation function: INR、PT、APTT<1.5 times the upper limit of normal
9. Signed the informed consent form

Exclusion Criteria:

1. Unresolved grade 2 [(Common Terminology Criteria for Adverse Events (CTCAE 5.0)] or higher toxic reactions caused by previous anticancer treatments
2. Known allergic reaction (grade 3-4) to any ingredients or excipients of the therapy
3. Known history of malignancy, unless been cured and no recurrence for 5 years
4. Known history of radiation to head and neck
5. Active severe clinical infection (> National Cancer Institute (NCI)-CTCAE version 5.0 grade 2 infection)
6. Obvious cardiovascular abnormalities [such as myocardial infarction, superior vena cava syndrome, grade 2 or higher heart disease diagnosed according to the New York Heart Association (NYHA) classification 3 months before enrollment]
7. Patients receiving immunology-based treatment for any reason
8. Patients with a history of active bleeding, coagulopathy, or receiving coumarin anticoagulation therapy
9. Pregnant or lactating women
10. Known active hepatitis B or C. Active hepatitis B is defined as a known HBsA positive with HBV DNA≥500 IU/mL. Active hepatitis C is defined as a known hepatitis C antibody positive and a known amount of hepatitis C virus HCV RNA results greater than the lower limit of detection. The presence of other serious liver diseases, including chronic autoimmune liver disease, primary biliary cirrhosis or sclerosing cholangitis, alcoholic liver disease, or non-alcoholic steatohepatitis (NASH)
11. Complicated with severe, uncontrolled infection or known human immunodeficiency virus (HIV) infection, or diagnosed as acquired immunodeficiency syndrome (AIDS); or uncontrolled autoimmune disease; or history of allogeneic tissue/organ transplantation, stem cell or bone marrow transplantation, or solid organ transplantation
12. Participation in other clinical trials within 30 days before enrollment
13. Other situations that the investigator considers unsuitable with respect to participating in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control arm; Standard therapy of radical surgery +adjuvant therapy (radiation/chemoradiation)
Experimental: Experimental arm; Neoadjuvant immunochemotherapy (albumin paclitaxel+cisplatin+tislelizumab) + radical surgery + adjuvant therapy (radiation/chemoradiation + tislelizumab maitainance)	Drug: albumin paclitaxel, cispatin, tislelizumab; Neoadjuvant immunochemotherapy (2 cycles, and 21 days each cycle, 260mg/m2 albumin paclitaxel intravenously on day 1 and day 22, with 75mg/m2 of cisplatin and 200mg of tislelizumab) + radical surgery + adjuvant therapy (radiation/chemoradiation followed by 200mg of tislelizumab, every 3 weeks for one year)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of 2-year event-free survival	Event free survival is calculated from the date of randomization to local recurrence, regional recurrence, distant metastasis, disease progress, or death. The rate of 2-year event free survival is reported as the percentage of patients who are event free survival for 2 years from the date of randomization.	2 years
Rate of 2-year overall survival	Overall survival is calculated from the date of randomization to death. The rate of 2-year overall survival is reported as the percentage of patients who are overall survival for 2 years from the date of randomization.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of 2-year disease-free survival	Disease free survival is calculated from the date of randomization to local recurrence, locoregional recurrence, distant metastasis, or death. The rate of 2-year disease free survival is reported as the percentage of patients who are disease free survival for 2 years from the date of randomization.	2 years
Rate of major pathological response	Major pathological response is based on the pathological examination on the post-operative specimens after neoadjuvant immunochemotherapy. The rate of major pathological response is reported as the percentage of patients who have major pathological response after NAT.	6 months

Collaborators and Investigators

• Sponsor: Lai-ping Zhong
• Collaborators: Sun Yat-sen University; Fudan University; Fujian Medical University; Central South University
• Investigators: Principal Investigator: Lai-ping Zhong, MD, PhD, Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 13, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Oral squamous cell carcinoma; Neoadjuvant immunochemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Tislelizumab; Paclitaxel
• Other Study ID Numbers: TopHill

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the completion of the trial.
• IPD Sharing Time Frame: 2 years after completion of the trial, for 6 months.
• IPD Sharing Access Criteria: Access to IPD data can be obtained upon scientifically sound request from the study PI, who will contact the Clinical Research Unit, Huashan Hospital, Fudan University. Access will be released after the approval from the Clinical Research Unit.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• 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