Clinical Study of Neoadjuvant PD-1 Antibody (Toripalimab) Plus Chemotherapy for Locally Advanced Thymic Epithelial Tumor
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Major pathologic response (MPR)
研究概览
简要总结
This is a phase II, single-arm, open-label study to evaluate the efficacy and safety of neoadjuvant Toripalimab + chemotherapy followed by radical surgery as first-line treatment in patients with locally advanced thymic epithelial tumor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Thymic epithelial tumor confirmed by needle biopsy;
- •No systemic metastasis confirmed by PET-CT;
- •Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or
- •At stage III-IVA (masaoka-koga) as identified by chest CT or MRI;
- •With the feasibility or anticipated feasibility after neoadjuvant therapy to receive radical surgery;
- •Aged 18-75 years;
- •At least 1 measurable lesion according to RECIST 1.1;
- •Patients with good function of other main organs (liver, kidney, blood system, etc.):
- •ANC count ≥1.5×10^9/L, platelet count ≥100×10^9/L，hemoglobin ≥90 g/L;
- •the international standard ratio of prothrombin time (INR) and prothrombin time (PT) < 1.5 times of upper limit of normal (ULN);
- •partial thromboplastin time (APTT) ≤1.5×ULN;
- •total bilirubin ≤1.5×ULN;
- •alanine aminotransferase (ALT) aspartate aminotransferase (AST) ≤2.5×ULN, or ALT and AST ≤5×ULN in the patients with liver metastatic tumor.
- •The child-bearing female must undergo pregnancy test within 7 days before starting the treatment and the result shall be negative. Reliable contraceptive measures, such as intrauterine device, contraceptive pill and condom, shall be adopted during the trial and within 30 days after completion of the trial. The child-bearing male shall use condom for contraception during the trial and within 30 days after completion of the trial;
- •The patient shall sign the Informed Consent Form.
排除标准
- •Participants who have received any systemic anti-cancer treatment for thymic epithelial tumor, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment and experimental treatment;
- •Administration of any Chinese medicine against cancer before administration of the drug;
- •Participants with other cancer (excluding cervical carcinoma in situ, cured basal cell carcinoma, bladder epithelial tumor [including TA and tis]) within five years before the start of this study;
- •Participants with any unstable systemic disease (including active infection, uncontrolled hypertension), unstable angina pectoris, angina pectoris starting in the last three months, congestive heart failure (>= NYHA) Grade II), myocardial infarction (6 months before admission), severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases;
- •With activate or suspectable autoimmune disease, or autoimmune paracancer syndrome requiring systemic treatment;
- •Antibiotics were used to treat the infection for 4 weeks prior to the start of the trial;
- •Participants who were systemically treated with corticosteroids (prednisone or other corticosteroids >10 mg/ day) or other immunosuppressive agents within 2 weeks prior to first administration. In the absence of active autoimmune disease, inhaled or topical corticosteroids and adrenal hormone replacement therapy with a dose of less than 10 mg/ day of prednisone are permitted;
- •Participants who are allergic to the test drug or any auxiliary materials;
- •Participants with active hepatitis B, hepatitis C or HIV;
- •The vaccine was administered within 4 weeks of the start of the trial;
- •Participants who have undergone major surgery or severe trauma in other systems within 2 months before the start of this trial;
- •Pleural effusion, pericardial effusion or ascites that are not clinically controlled and require pleural puncture or abdominal puncture drainage within 2 weeks before inclusion;
- •The patients have active pia meningioma, uncontrolled or untreated brain metastases;
- •Pregnant or lactating women;
- •Participants suffering from nervous system diseases or mental diseases that cannot cooperate;
- •Participated in another therapeutic clinical study;
- •Other factors that researchers think it is not suitable for enrollment.
研究组 & 干预措施
Thymic Epithelial Tumor
For thymoma:
Neoadjuvant treatment stage: Toripalimab 240mg, q3w, i.v., 2-4 cycles; platinum-based chemotherapy (Carboplatin AUC 5, Amycin 50mg/m2, Cyclophosphamide 500mg/m2) q3w, i.v., 2-4 cycles, then receive chest CT evaluation.
Surgery stage: the patients will receive radical surgery after the neoadjuvant treatment.
Adjuvant treatment stage: the patients who did not receive 4 cycle therapy will receive 1-2 cycles therapy up to 4 cycles in total, the following therapy is according to the NCCN guidelines.
For thymic carcinoma:
Neoadjuvant treatment stage: Toripalimab 240mg, q3w, i.v., 2-4 cycles; platinum-based chemotherapy (Cisplatin 50mg/m2, Paclitaxel 200mg/m2) q3w, i.v., 2-4 cycles, then receive chest CT evaluation.
干预措施: Toripalimab + Chemotherapy (Drug)
结局指标
主要结局
Major pathologic response (MPR)
时间窗: up to 4 months
MPR is defined as the proportion of participants who have achieved major pathologic response (on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants who have completed the neoadjuvant therapy before surgery.
Safety: frequency of severe adverse events
时间窗: up to 5 months
The frequency of severe adverse events from the participants enrolling to 30 days after the last drug administration or 30 days after surgery or new anti-cancer therapy, which comes first.
次要结局
- Objective response rate (ORR)(up to 4 months)
- Overall survival (OS)(up to 60 months)
- Health related quality of life (HRQol)(up to 6 months)
- Disease-free survival (DFS)(up to 60 months)
研究者
Peng Zhang
Director of science and education department
Shanghai Pulmonary Hospital, Shanghai, China