Candonilimab and ATRA Acid for Prevention of Oral Cancer Recurrence in Patients With OPL

A Study of Candonilimab Combined With All-trans Retinoic Acid for Prevention of Oral Cancer Recurrence in Patients With High-risk Oral Precancerous Lesions.

The aim of this study is to involve high-risk patients with a history of malignant transformation in oral potentially malignant disorders. We will use a combination of Cardunil and all-trans retinoic acid for intervention. The effectiveness and safety of the combination therapy will be evaluated in the treatment of high-risk oral potentially malignant disorders, including the prevention of oral cancer recurrence and treatment of oral potentially malignant disorders. The findings of this study will provide evidence for tertiary prevention of oral cancer and the treatment of oral potentially malignant disorders.

Study Overview

• Status: Active, not recruiting
• Conditions: Oral Cavity Cancer; Premalignant Lesion
• Intervention / Treatment: Drug: Candonilimab and ATRA; Other: other treatment or observation

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: ≥18 years old.
2. Patients with a history of oral potentially malignant disorders and still presenting any of the following potential malignant manifestations upon oral examination: (1) oral mucosal leukoplakia, (2) oral mucosal morphological changes (thickening, proliferation, etc.), (3) gingival atrophy, dark red gums, (4) oral mucosal ulcers, (5) white tongue coating changes, (6) oral mucosal erythema, blood blisters, etc.
3. History of one occurrence of invasive oral cancer/carcinoma in situ, and have undergone curative treatment.
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-1.

5. Adequate function of important organs and bone marrow:

   1. Hematology parameters: absolute neutrophil count (ANC) ≥ 1.5×10^9/L, platelet count (PLT) ≥ 100×10^9/L, hemoglobin (HGB) ≥ 8g/dL.
   2. Liver function: total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN), alanine aminotransferase (ALT) and/or aspartate transferase (AST) ≤ 2.5×ULN.
   3. Renal function: serum creatinine (Cr) ≤ 1.5×ULN.
6. Written informed consent and willingness to comply with the protocol procedures and visits.

Exclusion Criteria:

1. Patients who require adjuvant treatment such as radiation therapy or chemotherapy according to the assessment based on the malignant tumor treatment guidelines after the most recent oral cancer surgery (at least meeting any of the following criteria: T3-4, N2-3, DOI > 5mm, positive surgical margins/ < 5mm).
2. Patients who have undergone a major surgery or have unhealed wounds, ulcers, or fractures within 4 weeks before the first dose of study treatment.
3. Patients who received the last dose of radiotherapy or last dose of anti-tumor treatment (chemotherapy, targeted therapy, or tumor embolization, etc.) within 4 weeks before the first dose of study treatment.
4. History of exposure to any anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies.
5. Concurrent participation in another interventional clinical study, unless participating in an observational (non-interventional) clinical study or in the follow-up phase of an interventional study.
6. Use of any investigational drug within 4 weeks before the first dose of study treatment.
7. Use of immunosuppressive medication within 4 weeks before the first dose of study treatment, excluding intranasal, inhaled, or topical corticosteroids or systemic corticosteroids at physiologic doses (≤ 10 mg/day prednisone or equivalent dose of other corticosteroids).
8. Vaccination with live attenuated vaccines within 4 weeks before the first dose of study treatment or planned administration during the study.
9. Active, known, or suspected autoimmune diseases or medical history of such diseases within the past 2 years (excluding vitiligo, psoriasis, alopecia, or Grave's disease that do not require systemic treatment within the past 2 years, well-controlled hypothyroidism requiring thyroid hormone replacement, and type 1 diabetes mellitus requiring insulin replacement therapy).
10. Confirmed immunodeficiency disease.
11. History of allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
12. Known allergy to any monoclonal antibody component.
13. Uncontrolled severe diseases.

14. Coexistence of other malignancies, except for:

    1. Cured malignancy (e.g., papillary thyroid carcinoma).
    2. Non-melanoma skin cancer or malignancy resembling melanoma with no evidence of disease recurrence after adequate treatment.
    3. Carcinoma in situ with no evidence of disease recurrence after adequate treatment.
15. Pregnant or lactating patients. 5.4 Exclusion and Withdrawal Criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention with Candonilimab and ATRA; Candonilimab at a dose of 6mg/kg IV Q3W will be administered until a maximum treatment duration of 1 year. All-trans retinoic acid will be administered at a dose of 25mg/m² twice daily on days 1-14, with a treatment cycle of 21 days, until a maximum treatment duration of 6 months, or until the occurrence of oral cancer or other malignancies, death, intolerable toxicity, withdrawal of informed consent, or any other reasons specified in the protocol.	Drug: Candonilimab and ATRA; Candonilimab at a dose of 6mg/kg IV Q3W will be administered until a maximum treatment duration of 1 year. All-trans retinoic acid will be administered at a dose of 25mg/m² twice daily on days 1-14, with a treatment cycle of 21 days, until a maximum treatment duration of 6 months, or until the occurrence of oral cancer or other malignancies, death, intolerable toxicity, withdrawal of informed consent, or any other reasons specified in the protocol.
Other: mixed arm; Routine follow-up or treatment methods other than those in the intervention group of this study	Other: other treatment or observation; other treatment other than Candonilimab/ATRA or observation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
oral-cancer free survival，OCFS	2-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical response rate	clinical response rate of oral premalignant lesions	2-year
Safety Profile	Adverse Events of The Treatment	3 months
Quality-of-Life	EORTC QLQ-C30	1 year
overall survival, OS		2-year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2020
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 8, 2024
• First Submitted That Met QC Criteria: December 8, 2024
• First Posted (Actual): December 11, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 20, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Head and Neck Neoplasms; Recurrence; Mouth Neoplasms; Precancerous Conditions
• Other Study ID Numbers: 2024HNRT01

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