Sintilimab to Prevent High-risk Oral Premalignant Lesions Cancerization (STOP)

A Phase II Open-label, Single Arm Study to Evaluate the Efficacy of Sintilimab(IBI 308) to Prevent High-risk Oral Premalignant Lesions Cancerization

This is a non-randomized, phase II, open-label study. The goal of this clinical research study is to investigate how well sintilimab works in preventing high-risk oral premalignant lesions cancerization.

Study Overview

• Status: Unknown
• Conditions: Precancerous Conditions; Oral Cavity Cancer; Mouth Neoplasm
• Intervention / Treatment: Drug: Sintilimab

Detailed Description

this study is a non-randomized, phase II, open-label study. Phase II clinical trials test the safety and effectiveness of an investigational drug or combination of drugs to learn whether it works in preventing or treating a disease.

the purpose of this study is to evaluate the effectiveness of sintilimab in preventing the onset of oral cancer in patients with high-risk oral premalignant lesions, who had oral cancer at least once before.

• Study Type: Interventional
• Enrollment (Anticipated): 29
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Guopei Zhu; Phone Number: +8602164175590; Email: antica@gmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • Shanghai Ninth People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18
2. Histological evidence of oral premalignant lesions (such as leukoplakia and/or erythroplakia). A history of invasive oral cancer or oral cancer in situ, which was histologically confirmed.
3. With at least on high-risk profiles: a. have LOH at 3p14 and/or 9p21; b. pathologically diagnosis with severe dysplasia; c. size of lesions >200mm².
4. Eastern Cooperative Oncology Group Performance Status (ECOG) performance scale: 0-1.

5. Adequate organ and bone marrow function:

   • CBC: absolute neutrophil count (ANC) ≥ 1.5 × 10^9 / L; platelet count (PLT) ≥ 100 × 10^9 / L; hemoglobin content (HGB) ≥ 9.0 g / dL.
   • Liver function: serum total bilirubin (TBIL) ≤ 1.5 × normal upper limit (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
   • Renal function: serum creatinine (Cr) ≤ 1.5 × ULN.
6. Female subject of childbearing potential should have a negative urine or serum pregnancy test < 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
7. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of study therapy through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses > 1 year.
8. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of the study therapy.
9. Voluntarily signed written informed consent form, willing and able to comply with scheduled visits and other requirements of the study.

Exclusion Criteria:

1. Should receive subsequent adjuvant therapy (such as radiotherapy, chemotherapy, immunotherapy)
2. Received major surgery (such as craniotomy, thoracotomy or laparotomy) within 4 weeks of the first dose of study drugs or open wound, ulcer or fracture.
3. Received any anti-tumor therapy (chemotherapy, targeted therapy, tumor immunotherapy or arterial embolization) or radiotherapy within 4 weeks of the first dose of study treatment.
4. Prior therapy with anti-PD-1,anti-PD-L1,anti-CTLA4 antibody.
5. Currently participating in interventional clinical research treatment, or receiving other research medications within 4 weeks prior to the first dose or used research equipment
6. Received any investigational agent within 4 weeks of the first dose of study treatment.
7. Received radiotherapy within 4 weeks of the first dose of study treatment. Received systemic treatment with high-dose corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive drugs within 4 weeks of first dose. Inhaled or topical steroids and adrenal replacement steroid are permitted in the absence of active autoimmune disease.
8. Received attenuated live vaccine within 4 weeks of the first dose of study medication or plan to receive live vaccine during the study period.
9. Subjects with active, known or suspected autoimmune disease such as interstitial pneumonia, uveitis, Crohn's disease, autoimmune thyroiditis. Subjects with cured childhood asthma, type I diabetes mellitus and hypothyroidism only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment.
10. Known history of allogeneic organ or allogeneic hemopoietic stem cell transplantation
11. Known allergic or hypersensitive to docetaxel, any monoclonal antibody or any other components used in their preparation.

12. Uncontrolled concomitant disease, including but not limited to :

    • Active or poorly controlled severe infection
    • Human Immunodeficiency Virus (HIV) infection (HIV antibody positive)
    • Known acute or chronic active hepatitis B (HBV DNA positive) infection or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive) infection
    • Active tuberculosis
    • Symptomatic congestive heart failure (New York Heart Association grade III-IV) or symptomatic, poorly controlled arrhythmia
    • Uncontrolled hypertension (SBP ≥ 160mmHg or DBP ≥ 100mmHg)
    • Prior arterial thromboembolism event, including myocardial infarction, unstable angina, stroke, and transient ischemic attack, within 6 months of enrollment
13. Known history of, or any evidence of active, non-infectious pneumonitis.
14. Other primary malignancy, with the exception of the skin or squamous cell carcinoma of the skin or in situ cervical cancer.
15. Women who are pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sintilimab; Injection; dosage form: 10ml: 100mg; frequency: 200mgQ3W; duration: 8cycles (6 months) or randomization to the date of the first documented oral cancer incidence	Drug: Sintilimab; Sintilimab is a type of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells. other name: IBI308; Other Names: IBI308

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
oral cancer incidence rate	The proportion of patients who has been diagnosed with oral cavity cancer	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical response rate of oral premalignant lesions	The proportion of patients whose oral premalignant lesions experienced a Complete Response or a Partial Response	2 years
pathologically response rate of oral premalignant lesions	The proportion of patients whose oral premalignant lesions experienced a locally complete response or decrease of histopathological grade	2 years
Duration of Response (DoR) of oral premalignant lesions	the time from the date for first documented response of complete response (CR) or partial response (PR) until the date for the first documented response of progressive disease (PD), incidence of oral cancer or death in the absence of progression.	2 years
2 year oral-cancer-free survival	time from randomization to the development of histologically confirmed oral cancer or death of any cause, whichever occurs first	2 years
Treatment-related Adverse Events (AEs)	The grade of AEs and the number of patients with AEs are assessed by the investigator based on CTCAE v4.0 from the date of randomization to 90 days after last dose of study treatment	From the date of randomization to 90 days after last dose of study treatment
Overall survival (OS)	OS (per RECIST 1.1 as assessed by the investigator) is defined as the time from the date of randomisation until death due to any cause.	2 year
quality of life(QOL)	EORTC QLQ-C30 questionnaires	2 years

Collaborators and Investigators

• Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 15, 2019
• Primary Completion (ANTICIPATED): July 15, 2022
• Study Completion (ANTICIPATED): December 30, 2022

Study Registration Dates

• First Submitted: August 5, 2019
• First Submitted That Met QC Criteria: August 21, 2019
• First Posted (ACTUAL): August 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 22, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: sintilimab; high-risk oral pre-malignant lesions; history of invasive oral cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Precancerous Conditions; Mouth Neoplasms
• Other Study ID Numbers: 2019HNRT01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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