Clinical trial NCT06728631: Candonilimab and ATRA Acid for Prevention of Oral Cancer Recurrence in Patients With OPL
Official title: A Study of Candonilimab Combined With All-trans Retinoic Acid for Prevention of Oral Cancer Recurrence in Patients With High-risk Oral Precancerous Lesions.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Oral Cavity Cancer
Premalignant Lesion
Lead sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Sponsor class: OTHER
First posted: 2024-12-11
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: The mixed control group includes patients who have previously experienced at least one instance of oral cancer and are also diagnosed with oral precancerous lesions. These patients will undergo routine follow-up or treatments other than the interventions used in this study's experimental group.
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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 \&gt; 5mm, positive surgical margins/ \&lt; 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.

Primary outcomes:
measure: oral-cancer free survival，OCFS
timeFrame: 2-year
Secondary outcomes:
measure: clinical response rate
timeFrame: 2-year
measure: Safety Profile
timeFrame: 3 months
measure: Quality-of-Life
timeFrame: 1 year
measure: overall survival, OS
timeFrame: 2-year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital
Study officials:
References: