Clinical trial NCT05069857: Neoadjuvant Personalized Anti-PD-1 and Anti-VEGFR Therapy in OSCC Patients
Official title: Neoadjuvant Personalized Anti-PD-1 Therapy With Combination of Anti-VEGFR Therapy in Locally Advanced and Resectable Oral Squamous Cell Carcinoma: A Randomized Controlled Phase II Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Oral Squamous Cell Carcinoma
Neoadjvant Therapy
Anti-PD-1
Anti-VEGFR
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2021-10-06
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy of neoadjuvant anti-PD-1 plus anti-VEGFR therapy for patients with locally advanced and resectable oral squamous cell carcinoma, and the CPS\>10 in the biopsy samples.

Detailed description: In the previous "Icemelting" trial, neoadjuvant anti-PD-1 plus anti-VEGFR therapy was used in 20 patients with locally advanced and resectable oral squamous cell carcinoma (OSCC), and the neoadjuvant therapy was well-tolerated, with no grade 3-4 toxicity. The MPR rate was 40% (8/20), including 5% (1/20) pathological complete response; furthermore, in the patients with CPS\>10, the MPR rate was 100%. As we know, the MPR might transfer to survival benefit in the patients received neoadjuvant therapy. Therefore, in this randomized phase II trial, we aimed to evaluate the survival benefit of neoadjuvant anti-PD-1 plus anti-VEGFR therapy in the patients with locally advanced OSCC and CPS\>10 (Icemelting-2 trial). A total of 46 patients will be enrolled in this trial, and the primary endpoint is 2-year disease-free survival rate. The neoadjuvant therapy arm will receive three cycles of Carrelizumab plus Apatinib with 14 days each, followed by the standard treatment of surgery and postoperative adjuvant therapy. The control arm will received the standard treatment of surgery and postoperative adjuvant therapy.

Eligibility criteria: Inclusion Criteria:

1. Age: 18 to 75
2. Gender: Male and female
3. ECOG Score: 0-2
4. Histologically confirmed primary oral squamous cell carcinoma (including tongue, gingival, buccal, oral base, hard palate, posterior molar area)
5. Clinical stage III/IVA (cT1-2/N1-2/M0 or cT3-4a/N0-2 /M0, AJCC 8th)
6. The combined positive score (CPS score) of PD-L1 expression \> 10
7. Has signed informed consent

Exclusion Criteria:

1. Toxicity of ≥ grade 2 (CTCAE 5.0) that has not subsided due to previous anticancer therapy
2. Obvious cardiovascular abnormalities (such as myocardial infarction, superior vena cava syndrome, ≥ grade 2 heart disease diagnosed according to the NYHA classification criteria within 3 months prior to enrollment)
3. Active severe clinical infection (\> NCI-CTCAE Version 5.0 level 2 infection)
4. Uncontrollable hypertension (systolic blood pressure \> after antihypertensive medication; 150mmHg and/or diastolic blood pressure \> 90mmHg) or clinically significant (such as activity) cardiovascular disease, such as cerebrovascular accident (≤ 6 months before screening), myocardial infarction (≤ 6 months before screening), unstable angina, congestive heart failure rated class II or above by NYHA, or severe arrhythmias that cannot be controlled or have a potential impact on trial treatment
5. Blood routine examination: WBC \< 3,000/mm3, hemoglobin \< 8g/L, platelet \< 80,000/mm3
6. Liver function: ALAT/ASAT \> 2.5 times the normal upper limit, bilirubin \> 1.5 times the normal upper limit
7. Renal function: serum creatinine \> 1.5 times the normal upper limit
8. Has a history of maxillofacial and neck radiotherapy
9. Pregnant or lactating women
10. Participation in other clinical studies within 30 days prior to enrollment
11. Other conditions that the investigator considers inappropriate for participation

Primary outcomes:
measure: 2-year disease-free survival rate
timeFrame: 24 months
Secondary outcomes:
measure: 2-year overall survival rate
timeFrame: 24 months
measure: Major pathological response
timeFrame: 3 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
name: Lai-ping Zhong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: