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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Oral Squamous Cell Carcinoma; Anti-PD-1; Neoadjvant Therapy; Anti-VEGFR
• Intervention / Treatment: Drug: Camrelizumab (anti-PD-1 inhibitor); Drug: Apatinib (anti-VEGFR inhibitor)

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.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lai-ping Zhong, MD, PhD; Phone Number: 5160 +862123271699; Email: zhonglp@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 20011
      • Recruiting
      • Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Lai-ping Zhong, MD, PhD; Phone Number: 5160 +86-21-23271699; Email: zhonglaiping@163.com
      • Principal Investigator: Lai-ping Zhong, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant arm; The patients received three cycles of neoadjuvant therapy, with 14 days each. Dosage and administration: 200mg Carrelizumab intravenously on the first day of each cycle; Apatinib orally 250mg once a day from the first day of each cycle until the 9th day of the third cycle. Then the patients received the standard treatment of surgery and postoperative adjuvant therapy of radiotherapy or chemoradiotherapy.	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.; Drug: 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.
No Intervention: Control arm; The patients received the standard treatment of surgery and postoperative adjuvant therapy of radiotherapy or chemoradiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year overall survival rate	Overall survival was calculated from the date of randomization to death from any cause.	24 months
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

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Lai-ping Zhong, MD, PhD, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): August 30, 2024
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: September 24, 2021
• First Submitted That Met QC Criteria: September 25, 2021
• First Posted (Actual): October 6, 2021

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Apatinib; Immune Checkpoint Inhibitors
• Other Study ID Numbers: Icemelting-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study protocol and the primary study report might be shared depending on the condition of trial completion.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No