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

Oral Squamous Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06009861
• Other study ID #: PKUSSIRB-202386047
• Status: Recruiting
• Phase: Phase 2
• Start date: June 27, 2023
• Est. completion date: August 31, 2027

Study information

• Verified date: August 2023
• Source: Peking University Hospital of Stomatology
• Contact: Jie Zhang
• Phone: +86 10 82195246
• Email: zhangjie123[@]bjmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: August 31, 2027
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Tislelizumab
Dose: 200 mg Route: Intravenous infusion Frequency & treatment mode: Day 1, every 3 weeks
• Albumin-Bound Paclitaxel
Dose: 260 mg/m^2 Route: Intravenous infusion Frequency & treatment mode: Day 1, every 3 weeks
• Cisplatin
Dose: 60-75 mg/m^2 Route: Intravenous infusion Frequency & treatment mode: Day 1, every 3 weeks

Locations

Country	Name	City	State
China	Affiliated Hospital of Hebei University	Baoding	Hebei
China	Peking University School and Hospital Stomatology	Beijing	Beijing
China	The Hospital of Stomatology of Jilin University	Changchun	Jilin
China	Affiliated Hospital of Chifeng College	Chifeng	Inner Mongolia
China	The First Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	The Affiliated Hospital of Inner Mongolia Medical University	Hohhot	Inner Mongolia
China	Shandong Provincial Hospital	Jinan	Shandong
China	Shandong Provincial Hospital	Jinan	Shandong
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	China Medical University School and Hospital Of Stomatology	Shenyang	Liaoning
China	First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Shanxi Cancer hospital	Taiyuan	Shanxi
China	Tangshan People's Hospital	Tangshan	Hebei
China	Tianjin First Central Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Peking University Hospital of Stomatology

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 2 years
Secondary	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.	Up to 30 days post-surgery
Secondary	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.	Up to 30 days post-surgery
Secondary	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.	UP to 30 days prior-surgery
Secondary	Overall survival (OS)	OS is the time from randomization to death due to any cause.	Up to 2 years
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 per NCI-CTCAE V5.0.	Up to 2 years