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Neoadjuvant Tislelizumab Plus Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer (NeoSPOT)

Primary Purpose

Oral Squamous Cell Carcinoma, Oropharyngeal Squamous Cell Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tislelizumab
Albumin-Bound Paclitaxel
Cisplatin
Sponsored by
Peking University Hospital of Stomatology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oral Squamous Cell Carcinoma

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Cytological or histological diagnosis of initially or potentially surgically resectable Local advanced oral/oropharyngeal squamous cell carcinoma (stage III-IV). Plan to proceed neoadjuvant therapy. No prior anti-cancer treatment (include surgery, radiotherapy and systemic therapy) for oral/oropharyngeal squamous cell carcinoma. Clinically evaluable lesions per RECIST1.1. The age of signing the informed consent is 18-80 years old, regardless of gender. ECOG performance score 0-1. Estimated survival time≥6 months (this criterion overlaps with other inclusion criteria and must meet the following: ECOG score 0-1; Vital organ function meets the inclusion criteria in Article 8; Oral or oropharyngeal cancer does not involve the internal carotid artery; No subcutaneous metastases; No distant metastasis). Adequate organ function as follows: 1) Leukocyte count ≥ 3,000/mm3; 2) Absolute neutrophil count ≥ 1,500/mm3; 3) Platelet count ≥ 100,000/mm3; 4) Hemoglobin ≥ 90 g/L; 5) Serum creatinine ≤ 1.5 × ULN OR CrCl≥50 ml/min(Cockcroft-Gault); 6) Total bilirubin ≤ 1.5 × upper limit of normal (ULN); 7) AST (SGOT) and ALT (SGPT) < 2.5 × ULN; Subjects able and willing to follow research and follow-up procedures. For male and female subjects of childbearing age must agree to use adequate contraception throughout the study period and for 6 months after the end of treatment. Subjects voluntarily joined the clinical study and signed the informed consent. Exclusion Criteria: 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. History of allergy, and may have a potential allergy or intolerance to the investigational drug and its similar biologics. Participated in clinical trials of other antitumor drugs within 4 weeks prior to initial administration; Or receive live attenuated vaccine within 4 weeks prior to initial administration or during the study period; Subjects with concurrent other active malignancies. History of other types for cancer within past 5 years (exclude adequately treated skin squamous cell carcinoma or controlled skin basal cell carcinoma). Advanced subjects with symptoms, visceral dissemination, and a short-term risk of life-threatening complications (including uncontrolled massive exudation [pleural, pericardial, peritoneal], pulmonary lymphangitis, and more than 30% liver involvement). Subjects with active autoimmune disease or history of refractory autoimmune disease. Subjects with grade II or higher myocardial ischemia or myocardial infarction, uncontrolled arrhythmia (including QTc interval ≥450 ms in men and ≥470 ms in women), NYHA class III-IV cardiac insufficiency, or left ventricular ejection fraction (LVEF) <50% on echocardiography, myocardial infarction within 6 months before enrollment, New York Heart Association class II or higher heart failure, uncontrolled angina, uncontrolled severe ventricular arrhythmia, clinically significant pericardial disease, or electrocardiogram suggestive of acute ischemia or active conduction system abnormalities; Severe infection (e.g. requiring intravenous antibiotics, antifungal or antiviral medication) within 4 weeks before first dose, or unexplained fever >38.5°C during screening/before first dose; Subjects with a history of abuse of psychotropic substances and unable to withdraw from them or with mental disorders; Subjects undergone major surgery or have an open wound or fracture within 4 weeks before the first dose; Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of detection of the analytical method) or co-infection of hepatitis B and hepatitis C; Central nervous system metastasis; Subjects with a history of genetic or acquired bleeding or coagulation dysfunction (eligibility criteria at the investigator's discretion); Other conditions that the investigator determined were inappropriate for participation in the study.

Sites / Locations

  • Peking University School and Hospital StomatologyRecruiting
  • Affiliated Hospital of Hebei UniversityRecruiting
  • Tangshan People's HospitalRecruiting
  • The First Affiliated Hospital of Harbin Medical UniversityRecruiting
  • Affiliated Hospital of Chifeng CollegeRecruiting
  • The Affiliated Hospital of Inner Mongolia Medical UniversityRecruiting
  • The Hospital of Stomatology of Jilin UniversityRecruiting
  • China Medical University School and Hospital Of StomatologyRecruiting
  • Shandong Provincial HospitalRecruiting
  • Shandong Provincial HospitalRecruiting
  • The Affiliated Hospital of Qingdao UniversityRecruiting
  • First Hospital of Shanxi Medical UniversityRecruiting
  • Shanxi Cancer hospitalRecruiting
  • Tianjin First Central HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant Tislelizumab plus chemotherapy and adjuvant RT or Tislelizumab plus CCRT

Arm Description

Neoadjuvant phase: Patients will receive neoadjuvant Tislelizumab in combination with Albumin-Bound Paclitaxel and Cisplatin Q3W for 2 cycles. Adjuvant phase: For High-risk group(non-R0 resection or extranodal extension (ENE) or Lymph node metastasis>5): Concurrent chemoradiotherapy followed by Tislelizumab Q3W for 14 cycles. For the other group: intensity-modulated radiation therapy.

Outcomes

Primary Outcome Measures

Rate of Event free survival (EFS) at 2 years
EFS is the time from the date of randomization to the date of first record of any of the following events: disease progression; local or distant recurrence as assessed with imaging or biopsy as indicated; or death due to any cause.

Secondary Outcome Measures

Major Pathological Response (mPR)
The proportion of participants with a major pathological response (mPR) as assessed by the Central Pathologist at the time of definitive surgery. mPR is defined as ≤10% invasive squamous cell carcinoma within the resected primary tumor specimen and all the sampled regional lymph nodes.
Pathological Complete Response (pCR)
Pathological complete response (pCR) is measured as the proportion of participants with a pathological complete response as assessed by the central pathologist at the time of definitive surgery. pCR is defined as having no residual invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes.
Overall response rate (ORR)
Overall response rate (ORR) is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria.
Overall survival (OS)
OS is the time from randomization to death due to any cause.
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 per NCI-CTCAE V5.0.

Full Information

First Posted
August 16, 2023
Last Updated
August 22, 2023
Sponsor
Peking University Hospital of Stomatology
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1. Study Identification

Unique Protocol Identification Number
NCT06009861
Brief Title
Neoadjuvant Tislelizumab Plus Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer (NeoSPOT)
Official Title
Neoadjuvant Chemoimmunotherapy With Tislelizumab, Albumin-bound Paclitaxel, and Cisplatin in Locally Advanced Oral/Oropharyngeal Squamous Cell Carcinoma: A Prospective, Multicenter, Single-arm Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 27, 2023 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
August 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking University Hospital of Stomatology

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Previous studies confirmed locally advanced oral/oropharyngeal squamous cell carcinoma (LA OSCC or OPSCC) patients with a pathological response had higher probability of survival in neoadjuvant settings. Several ongoing trials of neoadjuvant immunotherapy in head and neck cancer showed promising results. However, the optimal regimen remains unclear. This trial aimed to evaluate the efficacy and safety of neoadjuvant therapy with anti-programmed cell death 1 monoclonal antibody Tislelizumab and chemotherapy, followed by surgery and adjuvant radiotherapy or chemoradiotherapy plus Tislelizumab in LA OSCC or OPSCC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Squamous Cell Carcinoma, Oropharyngeal Squamous Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
110 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Neoadjuvant Tislelizumab plus chemotherapy and adjuvant RT or Tislelizumab plus CCRT
Arm Type
Experimental
Arm Description
Neoadjuvant phase: Patients will receive neoadjuvant Tislelizumab in combination with Albumin-Bound Paclitaxel and Cisplatin Q3W for 2 cycles. Adjuvant phase: For High-risk group(non-R0 resection or extranodal extension (ENE) or Lymph node metastasis>5): Concurrent chemoradiotherapy followed by Tislelizumab Q3W for 14 cycles. For the other group: intensity-modulated radiation therapy.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
Dose: 200 mg Route: Intravenous infusion Frequency & treatment mode: Day 1, every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Albumin-Bound Paclitaxel
Intervention Description
Dose: 260 mg/m^2 Route: Intravenous infusion Frequency & treatment mode: Day 1, every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Dose: 60-75 mg/m^2 Route: Intravenous infusion Frequency & treatment mode: Day 1, every 3 weeks
Primary Outcome Measure Information:
Title
Rate of Event free survival (EFS) at 2 years
Description
EFS is the time from the date of randomization to the date of first record of any of the following events: disease progression; local or distant recurrence as assessed with imaging or biopsy as indicated; or death due to any cause.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Major Pathological Response (mPR)
Description
The proportion of participants with a major pathological response (mPR) as assessed by the Central Pathologist at the time of definitive surgery. mPR is defined as ≤10% invasive squamous cell carcinoma within the resected primary tumor specimen and all the sampled regional lymph nodes.
Time Frame
Up to 30 days post-surgery
Title
Pathological Complete Response (pCR)
Description
Pathological complete response (pCR) is measured as the proportion of participants with a pathological complete response as assessed by the central pathologist at the time of definitive surgery. pCR is defined as having no residual invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes.
Time Frame
Up to 30 days post-surgery
Title
Overall response rate (ORR)
Description
Overall response rate (ORR) is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria.
Time Frame
UP to 30 days prior-surgery
Title
Overall survival (OS)
Description
OS is the time from randomization to death due to any cause.
Time Frame
Up to 2 years
Title
Adverse events (AEs)
Description
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 per NCI-CTCAE V5.0.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Cytological or histological diagnosis of initially or potentially surgically resectable Local advanced oral/oropharyngeal squamous cell carcinoma (stage III-IV). Plan to proceed neoadjuvant therapy. No prior anti-cancer treatment (include surgery, radiotherapy and systemic therapy) for oral/oropharyngeal squamous cell carcinoma. Clinically evaluable lesions per RECIST1.1. The age of signing the informed consent is 18-80 years old, regardless of gender. ECOG performance score 0-1. Estimated survival time≥6 months (this criterion overlaps with other inclusion criteria and must meet the following: ECOG score 0-1; Vital organ function meets the inclusion criteria in Article 8; Oral or oropharyngeal cancer does not involve the internal carotid artery; No subcutaneous metastases; No distant metastasis). Adequate organ function as follows: 1) Leukocyte count ≥ 3,000/mm3; 2) Absolute neutrophil count ≥ 1,500/mm3; 3) Platelet count ≥ 100,000/mm3; 4) Hemoglobin ≥ 90 g/L; 5) Serum creatinine ≤ 1.5 × ULN OR CrCl≥50 ml/min(Cockcroft-Gault); 6) Total bilirubin ≤ 1.5 × upper limit of normal (ULN); 7) AST (SGOT) and ALT (SGPT) < 2.5 × ULN; Subjects able and willing to follow research and follow-up procedures. For male and female subjects of childbearing age must agree to use adequate contraception throughout the study period and for 6 months after the end of treatment. Subjects voluntarily joined the clinical study and signed the informed consent. Exclusion Criteria: 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. History of allergy, and may have a potential allergy or intolerance to the investigational drug and its similar biologics. Participated in clinical trials of other antitumor drugs within 4 weeks prior to initial administration; Or receive live attenuated vaccine within 4 weeks prior to initial administration or during the study period; Subjects with concurrent other active malignancies. History of other types for cancer within past 5 years (exclude adequately treated skin squamous cell carcinoma or controlled skin basal cell carcinoma). Advanced subjects with symptoms, visceral dissemination, and a short-term risk of life-threatening complications (including uncontrolled massive exudation [pleural, pericardial, peritoneal], pulmonary lymphangitis, and more than 30% liver involvement). Subjects with active autoimmune disease or history of refractory autoimmune disease. Subjects with grade II or higher myocardial ischemia or myocardial infarction, uncontrolled arrhythmia (including QTc interval ≥450 ms in men and ≥470 ms in women), NYHA class III-IV cardiac insufficiency, or left ventricular ejection fraction (LVEF) <50% on echocardiography, myocardial infarction within 6 months before enrollment, New York Heart Association class II or higher heart failure, uncontrolled angina, uncontrolled severe ventricular arrhythmia, clinically significant pericardial disease, or electrocardiogram suggestive of acute ischemia or active conduction system abnormalities; Severe infection (e.g. requiring intravenous antibiotics, antifungal or antiviral medication) within 4 weeks before first dose, or unexplained fever >38.5°C during screening/before first dose; Subjects with a history of abuse of psychotropic substances and unable to withdraw from them or with mental disorders; Subjects undergone major surgery or have an open wound or fracture within 4 weeks before the first dose; Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of detection of the analytical method) or co-infection of hepatitis B and hepatitis C; Central nervous system metastasis; Subjects with a history of genetic or acquired bleeding or coagulation dysfunction (eligibility criteria at the investigator's discretion); Other conditions that the investigator determined were inappropriate for participation in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jie Zhang
Phone
+86 10 82195246
Email
zhangjie123@bjmu.edu.cn
Facility Information:
Facility Name
Peking University School and Hospital Stomatology
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Zhang, Dr.
Phone
+86 10 82195382
Email
zhangjie06@126.com
First Name & Middle Initial & Last Name & Degree
Wenjie Wu, Dr.
Facility Name
Affiliated Hospital of Hebei University
City
Baoding
State/Province
Hebei
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhizheng Zhuang, Dr.
Facility Name
Tangshan People's Hospital
City
Tangshan
State/Province
Hebei
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chenglin Dai, Dr.
Facility Name
The First Affiliated Hospital of Harbin Medical University
City
Harbin
State/Province
Heilongjiang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jichen Li, Dr.
Facility Name
Affiliated Hospital of Chifeng College
City
Chifeng
State/Province
Inner Mongolia
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pengfei Ma, Dr.
Facility Name
The Affiliated Hospital of Inner Mongolia Medical University
City
Hohhot
State/Province
Inner Mongolia
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bateer Delehei, Dr.
Facility Name
The Hospital of Stomatology of Jilin University
City
Changchun
State/Province
Jilin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qilin Liu, Dr.
Facility Name
China Medical University School and Hospital Of Stomatology
City
Shenyang
State/Province
Liaoning
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fayu Liu, Dr.
Facility Name
Shandong Provincial Hospital
City
Jinan
State/Province
Shandong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shizhou Zhang, Dr.
Facility Name
Shandong Provincial Hospital
City
Jinan
State/Province
Shandong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weidong Zhang, Dr.
Facility Name
The Affiliated Hospital of Qingdao University
City
Qingdao
State/Province
Shandong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Shang, Dr.
Facility Name
First Hospital of Shanxi Medical University
City
Taiyuan
State/Province
Shanxi
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xinrong Nan, Dr.
Facility Name
Shanxi Cancer hospital
City
Taiyuan
State/Province
Shanxi
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fei Han, Dr.
Facility Name
Tianjin First Central Hospital
City
Tianjin
State/Province
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yongdong Zhang, Dr.

12. IPD Sharing Statement

Plan to Share IPD
No

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Neoadjuvant Tislelizumab Plus Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer (NeoSPOT)

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