A Phase 2 Randomized Clinical Trial to Examine the Efficacy of Carbon-Ion Radiotherapy Plus Camrelizumab As Salvage Treatment for Locally Recurrent Nasopharyngeal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 146
- 试验地点
- 1
- 主要终点
- Progression-free survival
研究概览
简要总结
The purpose of this trial is to examine the role of camrezlizumab in addition to carbon-ion radiotherapy (CIRT) for patients with locally recurrent nasopharyngeal carcinoma. According to the plan, a total of 146 patients will be recruited and randomized into: 1) CIRT alone group (control group); 2) CIRT plus camrelizumab group (experimental group).
详细描述
Treatment for locally recurrent nasopharyngeal carcinoma (LR-NPC) is challenging. Carbon-ion radiotherapy appeared to be an effective treatment for this group of patients, and has substantially improved the 2-year overall survival (OS) to approximately 85%, compared to photon-based intensity-modulated radiotherapy. However, a group of the patients may still develop disease progression after CIRT, and the 2-year progression-free survival (PFS) was approximately 45%-50%. Camrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been demonstrated that it is effective in the recurrent/metastatic nasopharyngeal carcinoma; however, the role of camrelizumab in concurrence with radiotherapy, especially CIRT, for LR-NPC is not clear. The purpose of this phase 2 clinical trial is to compare the efficacy of CIRT plus camrelizumab and CIRT alone in the treatment of LR-NPC. Eligible participants will be randomized (1:1) to 1) CIRT alone group (control group); 2) CIRT plus camrelizumab group (experimental group). The primary endpoint is progression-free survival. Secondary endpoints include overall survival (OS), local progression-free survival (LPFS), regional progression-free survival (RPFS), and distant metastasis-free survival (DMFS) and toxicities. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completed a definitive course of intensity-modulated photon radiation therapy (IMRT) to a total dose of ≥ 66 Gy
- •Recurrence at nasopharynx diagnosed more than 6 months after the initial course of IMRT
- •Patients with neck lymphadenopathy should receive neck dissection before randomization
- •With measurable lesion on contrast MR scan
- •Age ≥ 18 and < 70 years of age
- •ECOG score: 0-1
- •Leucocyte count ≥ 4000/µL, neutrocyte count ≥ 2000/µL, platelet count ≥ 100000/µL, hemoglobin ≥ 90g/L
- •Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) < 1.5×upper limit of normal (ULN), alkaline phosphatase < 2.5×ULN, bilirubin ≤ ULN, serum creatinine ≤ ULN, creatinine clearance ≥ 60ml/min
- •Willing to accept adequate contraception
- •Ability to understand the nature of the clinical trial and sign the written informed consent
排除标准
- •Presence of distant metastasis
- •Previously received radioactive particle implantation
- •Prior malignancy within 5 years before randomization, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer
- •Patients who received local (such as surgery and cryotherapy) or systemic treatment, except for induction chemotherapy after diagnosis of recurrence
- •With uncontrolled active infection
- •With pneumonia
- •With autoimmune disease
- •With a known history of testing positive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
- •Hepatitis B virus (HBV) DNA ≥ 500IU/mL for patients with positive HBV surface antigen, positive hepatitis C virus RNA for patients with positive HCV antigen
- •Previously treated by immune checkpoint inhibitors
- •Medical conditions requiring treatment of antibiotics and/or corticosteroid
- •Treated with ≥ 5 days antibiotics one month before start of immunotherapy
- •With known allergy to any of the study drugs
- •Pregnant or lactating women
- •Any severe intercurrent disease that may interfere with the current study
研究组 & 干预措施
Arm-C
Patients will receive induction chemotherapy followed by carbon-ion radiotherapy with a dose of 63 GyE in 21 fractions (the fraction size is 3 GyE).
干预措施: Induction chemotherapy (Drug)
Arm-C
Patients will receive induction chemotherapy followed by carbon-ion radiotherapy with a dose of 63 GyE in 21 fractions (the fraction size is 3 GyE).
干预措施: Carbon-ion radiotherapy (Radiation)
Arm-CC
Patients will receive induction chemotherapy followed by carbon-ion radiotherapy and camrelizumab. In details, patients will receive carbon-ion radiotherapy with a dose of 63 GyE in 21 fractions (the fraction size is 3 GyE); in addition, patients will also receive camrelizumab of 200 mg (IV.), every 2 weeks, started with carbon-ion radiotherapy for a maximal period of 1 year.
干预措施: Induction chemotherapy (Drug)
Arm-CC
Patients will receive induction chemotherapy followed by carbon-ion radiotherapy and camrelizumab. In details, patients will receive carbon-ion radiotherapy with a dose of 63 GyE in 21 fractions (the fraction size is 3 GyE); in addition, patients will also receive camrelizumab of 200 mg (IV.), every 2 weeks, started with carbon-ion radiotherapy for a maximal period of 1 year.
干预措施: Carbon-ion radiotherapy (Radiation)
Arm-CC
Patients will receive induction chemotherapy followed by carbon-ion radiotherapy and camrelizumab. In details, patients will receive carbon-ion radiotherapy with a dose of 63 GyE in 21 fractions (the fraction size is 3 GyE); in addition, patients will also receive camrelizumab of 200 mg (IV.), every 2 weeks, started with carbon-ion radiotherapy for a maximal period of 1 year.
干预措施: Camrelizumab (Drug)
结局指标
主要结局
Progression-free survival
时间窗: 2-year
Duration from randomization to documented disease recurrence or death from any cause, whichever occurs first.
次要结局
- Local progression-free survival(2-year)
- Overall survival(2-year)
- Regional progression-free survival(2-year)
- Number of participants with adverse events(2-year)
- Distant metastasis-free survival(2-year)
研究者
Jiade J. Lu
Prof.
Shanghai Proton and Heavy Ion Center