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

Primary Purpose

Oral Squamous Cell Carcinoma, Neoadjvant Therapy, Anti-PD-1

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Camrelizumab (anti-PD-1 inhibitor)
Apatinib (anti-VEGFR inhibitor)
Sponsored by
Shanghai Jiao Tong University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oral Squamous Cell Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Neoadjuvant arm

Control arm

Arm Description

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.

The patients received the standard treatment of surgery and postoperative adjuvant therapy of radiotherapy or chemoradiotherapy.

Outcomes

Primary Outcome Measures

2-year disease-free survival rate
Disease-free survival was calculated from the date of randomization to tumor recurrence or death from any cause.

Secondary Outcome Measures

2-year overall survival rate
Overall survival was calculated from the date of randomization to death from any cause.
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%.

Full Information

First Posted
September 24, 2021
Last Updated
October 8, 2022
Sponsor
Shanghai Jiao Tong University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT05069857
Brief Title
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

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2021 (Actual)
Primary Completion Date
August 30, 2023 (Anticipated)
Study Completion Date
June 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Jiao Tong University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Squamous Cell Carcinoma, Neoadjvant Therapy, Anti-PD-1, Anti-VEGFR

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
46 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Neoadjuvant arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Control arm
Arm Type
No Intervention
Arm Description
The patients received the standard treatment of surgery and postoperative adjuvant therapy of radiotherapy or chemoradiotherapy.
Intervention Type
Drug
Intervention Name(s)
Camrelizumab (anti-PD-1 inhibitor)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Apatinib (anti-VEGFR inhibitor)
Intervention Description
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.
Primary Outcome Measure Information:
Title
2-year disease-free survival rate
Description
Disease-free survival was calculated from the date of randomization to tumor recurrence or death from any cause.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
2-year overall survival rate
Description
Overall survival was calculated from the date of randomization to death from any cause.
Time Frame
24 months
Title
Major pathological response
Description
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%.
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age: 18 to 75 Gender: Male and female ECOG Score: 0-2 Histologically confirmed primary oral squamous cell carcinoma (including tongue, gingival, buccal, oral base, hard palate, posterior molar area) Clinical stage III/IVA (cT1-2/N1-2/M0 or cT3-4a/N0-2 /M0, AJCC 8th) The combined positive score (CPS score) of PD-L1 expression > 10 Has signed informed consent Exclusion Criteria: Toxicity of ≥ grade 2 (CTCAE 5.0) that has not subsided due to previous anticancer therapy 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) Active severe clinical infection (> NCI-CTCAE Version 5.0 level 2 infection) 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 Blood routine examination: WBC < 3,000/mm3, hemoglobin < 8g/L, platelet < 80,000/mm3 Liver function: ALAT/ASAT > 2.5 times the normal upper limit, bilirubin > 1.5 times the normal upper limit Renal function: serum creatinine > 1.5 times the normal upper limit Has a history of maxillofacial and neck radiotherapy Pregnant or lactating women Participation in other clinical studies within 30 days prior to enrollment Other conditions that the investigator considers inappropriate for participation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lai-ping Zhong, MD, PhD
Phone
+862123271699
Ext
5160
Email
zhonglp@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lai-ping Zhong, MD, PhD
Organizational Affiliation
Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
20011
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lai-ping Zhong, MD, PhD
Phone
+86-21-23271699
Ext
5160
Email
zhonglaiping@163.com
First Name & Middle Initial & Last Name & Degree
Lai-ping Zhong, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
The study protocol and the primary study report might be shared depending on the condition of trial completion.

Learn more about this trial

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

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