Clinical trial NCT06019468: Neoadjuvant Treatment For Locally Advanced Thymic Cancer
Official title: Clinical Study of Envolizumab Combined With Radiotherapy for Neoadjuvant Treatment of Locally Advanced Thymic Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Thymic Carcinoma
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
First posted: 2023-08-31
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aims of this study are to verify the feasibility, effectiveness, and safety of the combination of enrolizumab and radiotherapy for neoadjuvant treatment for locally advanced thymic carcinoma, and to provide recommendations for the establishment of unified evaluation criteria for the neoadjuvant therapy of thymic cancer by evaluating the pathological remission status of thymic cancer specimens after neoadjuvant treatment.

Detailed description: For patients with locally advanced thymic carcinoma, it is often difficult to perform radical resection. Numerous studies have reported that neoadjuvant therapy can improve the surgical resection rate of thymic tumors by reducing the extent of tumor invasion and eliminating small metastatic lesions, thereby improving patient survival. However, the efficacy of neoadjuvant immunotherapy combined with chemotherapy is limited. This study intends to conduct a single-arm, phase II clinical trial of neoadjuvant immunotherapy combined with radiotherapy for locally advanced thymic carcinoma to verify the feasibility and safety of neoadjuvant immunotherapy combined with radiotherapy. Meanwhile, the investigators evaluate the pathological remission of postoperative specimens to provide recommendations for establishing pathological evaluation criteria for neoadjuvant therapy for thymic carcinoma.

Eligibility criteria: Inclusion Criteria:

1. Pathologically confirmed as thymic carcinoma;
2. Clinical staging III-IVA (TNM staging system), non-myasthenia gravis (MG) patients, expected to undergo surgical resection;
3. On the day when the subject signs the informed consent form, they are ≥ 18 years old and\<75 years old, regardless of gender;
4. The subjects are able to understand the informed consent form, voluntarily participate, and sign the informed consent form;
5. Subjects who have not received any anti-thymic tumor treatment in the past, including but not limited to systemic chemotherapy, radiotherapy, or immunotherapy (only those who have received traditional Chinese medicine treatment for anti-tumor indications are allowed to be included, and a cleaning period of at least 2 weeks is required);
6. At least 1 measurable lesion (according to the solid tumor efficacy evaluation standard RECIST V1.1);
7. Physical fitness score of 0 or 1 (ECOG scoring system of the Eastern Cancer Collaborative Group in the United States);
8. Female subjects with fertility must have a negative serum pregnancy test within 7 days before the first administration;
9. Female subjects with fertility or male subjects with partners with fertility agree to use efficient contraceptive measures (with an annual failure rate of less than 1%) from 7 days before the first administration until 24 weeks after the end of administration;
10. The main organ functions within 7 days before the first administration meet the following standards:

    1. Bone marrow function: hemoglobin ≥ 10.0 g/dL (no blood transfusion received within 28 days before hemoglobin test), absolute neutrophil count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L (no platelet transfusion or IL-11 treatment received within 14 days prior to platelet count test);
    2. Coagulation function: INR and PT\<1.5 × ULN, APTT ≤ 1.5 × ULN;
    3. Liver function: transaminases (ALT and AST) ≤ 2.5 × ULN; Total bilirubin ≤ 1.5 × ULN (total bilirubin ≤ 2.5 in subjects with Gilbert's syndrome or liver metastasis) × ULN);
    4. Renal function: serum creatinine clearance rate ≥ 60 mL/min (calculated according to Cockcroft Fault formula);
    5. Adequate lung function: According to the doctor's judgment, lung function can meet the requirements of thymectomy surgery.

Exclusion Criteria:

1. Pathologically confirmed as a thymic neuroendocrine tumor;
2. Subjects who have undergone major surgical treatment (such as abdominal or thoracic surgery; excluding diagnostic puncture or peripheral vascular pathway replacement surgery) or have not recovered from surgical treatment within 28 days before the administration of this trial;
3. Within 14 days before the first administration of this study, systemic corticosteroids (≥ 10 mg/day prednisone, or equivalent amounts of other corticosteroids) or immunosuppressive therapy are required for 7 consecutive days; Excluding inhalation or local application of hormones, or receiving physiological replacement doses of hormone therapy due to adrenal insufficiency; Allow short-term (\<7 days) use of corticosteroids for prevention (such as contrast agent allergies) or treatment of non-autoimmune diseases (such as delayed hypersensitivity reactions caused by exposure to allergens);
4. Received live vaccines (including attenuated live vaccines) within 28 days prior to administration in this study;
5. Previously or currently suffering from interstitial pneumonia/lung disease that requires systemic hormone therapy;
6. Previously or currently suffering from autoimmune diseases, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener syndrome (granulomatosis of vasculitis, Graves disease, rheumatoid arthritis, pituitary inflammation, uveitis), autoimmune hepatitis, systemic sclerosis (scleroderma, etc.), Hashimoto's thyroiditis (exceptions see below), autoimmune vasculitis Autoimmune neuropathy (Guillain Barre syndrome), etc. The following cases are excluded: type I diabetes, hypothyroidism with stable hormone replacement therapy (including hypothyroidism caused by autoimmune thyroid disease), psoriasis or vitiligo without systemic treatment;
7. Other malignant tumors were combined within 5 years before the first administration, excluding cured skin squamous cell carcinoma, basal cell carcinoma, non-muscle invasive bladder cancer, localized low-risk prostate (defined as stage ≤ T2a, Gleason score ≤ 6, and PSA ≤ 10ng/mL at the time of diagnosis of prostate cancer (if measured, patients who have received radical treatment and have no PSA biochemical relapse can participate in this study), and in situ cervical/breast cancer;
8. Have uncontrolled heart, kidney, gastrointestinal tract, infectious diseases and other complications;
9. Previous history of allogeneic bone marrow or organ transplantation;;
10. Previously treated with any antibody/drug (immune checkpoint) targeting T cell co-regulatory proteins, such as anti PD (L) 1, CTLA-4, 4-1BB, LAG 3, TIM 3, or anti CD127; Previously received anti-tumor vaccine treatment
11. Previous history of allergic reactions to antibody-based drugs and intolerance (≥ Level 3 NCI-CTCAE V5.0); Any past history of rapid allergic reactions and uncontrollable asthma (i.e. uncontrollable asthma symptoms of 3 or more of the 3 or more characteristics of partially controlled asthma); Previous obvious allergies to drugs (such as severe allergic reactions, immune-mediated hepatotoxicity, immune-mediated thrombocytopenia or anemia);
12. Pregnant and/or lactating women;
13. Other situations that may affect the safety or compliance of drug treatment in this study, including but not limited to mental illness, uncontrolled large amounts of serous fluid accumulation, or subjects who require repeated drainage (recurrence within 2 weeks after intervention) with moderate to large amounts of serous fluid accumulation, cachexia, etc.

Primary outcomes:
measure: objective response rate（ORR）
timeFrame: 24 hour
Secondary outcomes:
measure: Disease control rate（DCR）
timeFrame: 24 hours
measure: Radical resection rate（R0）
timeFrame: 24 hours
measure: Pathological remission rate
timeFrame: 7 days
measure: disease-free survival（DFS）
timeFrame: 5 years
measure: overall survival（OS）
timeFrame: 5 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Pulmonary Hospital, School of Medicine, Tongji University
name: Deping Zhao, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: