Neoadjuvant Personalized Anti-PD-1 and Anti-VEGFR Therapy in OSCC Patients

Oral Squamous Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05069857
• Other study ID #: Icemelting-2
• Status: Recruiting
• Phase: Phase 2
• Start date: September 1, 2021
• Est. completion date: June 30, 2028

Study information

• Verified date: November 2023
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: Lai-ping Zhong, MD, PhD
• Phone: +862123271699
• Email: zhonglp[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: June 30, 2028
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Anti-PD-1
• Carcinoma
• Carcinoma, Squamous Cell
• Oral Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Camrelizumab (anti-PD-1 inhibitor)
The patients will receive three cycles of Camrelizumab, with 14 days each. 200mg of Carrelizumab will be used intravenously on the first day of each cycle.
• Apatinib (anti-VEGFR inhibitor)
The patients will receive Apatinib orally 250mg once a day from the first day of each cycle until the 9th day of the third cycle.

Locations

Country	Name	City	State
China	Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-year disease-free survival rate	Disease-free survival was calculated from the date of randomization to tumor recurrence or death from any cause.	24 months
Secondary	2-year overall survival rate	Overall survival was calculated from the date of randomization to death from any cause.	24 months
Secondary	Major pathological response	The major pathological response (MPR): the percentage of tumor cells before and after treatment was compared according to biopsy specimens before neoadjuvant therapy and pathological specimens after surgery; the percentage of residual viable tumor (RVT) cells was evaluated on resected tumor slides. MPR was defined as = 10% RVT%.	3 months