Clinical trial NCT06009861: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Oral Squamous Cell Carcinoma
Oropharyngeal Squamous Cell Carcinoma
Lead sponsor: Peking University Hospital of Stomatology
Sponsor class: OTHER
First posted: 2023-08-24
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Rate of Event free survival (EFS) at 2 years
timeFrame: Up to 2 years
Secondary outcomes:
measure: Major Pathological Response (mPR)
timeFrame: Up to 30 days post-surgery
measure: Pathological Complete Response (pCR)
timeFrame: Up to 30 days post-surgery
measure: Overall response rate (ORR)
timeFrame: UP to 30 days prior-surgery
measure: Overall survival (OS)
timeFrame: Up to 2 years
measure: Adverse events (AEs)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University School and Hospital Stomatology
state: Beijing
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Tangshan
country: China
facility: Tangshan People's Hospital
state: Hebei
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Chifeng
country: China
facility: Affiliated Hospital of Chifeng College
state: Inner Mongolia
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Changchun
country: China
facility: The Hospital of Stomatology of Jilin University
state: Jilin
city: Shenyang
country: China
facility: China Medical University School and Hospital Of Stomatology
state: Liaoning
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Cancer hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin First Central Hospital
state: Tianjin
Study officials:
References: