SBRT/LDRT in Combination With Camrelizumab and Apatinib in Metastatic Non-small Cell Lung Cancer Patient Previously Treated With PD-1/L1 Inhibitor and Chemotherapy
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT04878107
- Lead Sponsor
- Wuhan University
- Brief Summary
SABRE STUDY will explore effectiveness and safety of the combination therapy of camrelizumab，apatinib and SBRT/LDRT in patients with metastatic non-small Cell Lung Cancer (NSCLC) patient previously treated With PD-1/L1 Inhibitor and Chemotherapy.
- Detailed Description
SABRE STUDY consists of two stages.
first stage of this trial is a single-arm study that requires enrolling at least 18 patients, all of whom would receive the treatment of SBRT/LDRT in combination with apatinib plus camrelizumab.The trial would proceed into the second stage if 4 or more patients achieve CR/PR. Otherwise, the trial is stopped early due to futility as we fail to reject the null.
In the second stage, at least 70 patients are equally randomized into two arms to receive "SBRT/LDRT in combination with apatinib plus camrelizumab" or "SBRT + docetaxel" . Stratified-area group randomization would be used.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 88
- Histological or cytological diagnosis of non-small cell lung cancer（NSCLC）
- Has previous treatment with PD-1/L1 monoclonal antibody in combination with a platinum-based chemotherapy with outcome of complete remission (CR), partial remission (PR), or stable disease (SD) for ≥ 6 months
- Has at least two disseminated lesions for LDRT and SBRT, respectively
- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
- Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) or ROS Proto-Oncogene 1(ROS1)-directed therapy is not indicated
- Has adequate organ function
- For female subjects of childbearing potential, a serum pregnancy test should be performed within 7 days prior to the administration of the first study intervention (study drug, radiation therapy) and have a negative result. Subjects are required to agree to use highly effective contraception (i.e., a method with a failure rate of less than 1% per year) and continue until at least 180 days after discontinuation of trial treatment
- Imaging (CT or MRI) shows evidence of tumour invasion of large blood vessels or poorly demarcated blood vessels or the presence of cavities and necrotic lesions in the lungs
- With active bleeding or perforation or a hereditary or acquired bleeding tendency present, with a daily haemoptysis of ≥2.5mL in the 3 months prior to screening.
- with hypertensive disorders that cannot be reduced to the normal range with antihypertensive medication (systolic blood pressure ≤ 140 mmHg / diastolic blood pressure ≤ 90 mmHg).
- Urine routine suggesting urine protein ≥ (++) and 24-hour urine protein amount ≥ 1.0g.
- presence of thrombotic disease requiring long-term anticoagulation with warfarin or heparin, or requiring long-term antiplatelet therapy (aspirin ≥ 300 mg/day or clopidogrel ≥ 75 mg/day).
- Previous systemic antitumour therapy other than PD-1(L1) monoclonal antibody in combination with platinum-based chemotherapy, or previous treatment with anti-angiogenic agents (including bevacizumab, apatinib, anlotinib, etc.).
- Immune-related adverse events in previous PD-1(L1) therapy leading to treatment discontinuation
- Symptomatic, untreated or actively progressing central nervous system (CNS) metastases are confirmed by CT or MRI assessment during screening and prior to radiographic evaluation.
- Subjects with grade II or above myocardial ischemia or myocardial infarction and poorly controlled arrhythmias (QTc interval > 450 ms for males and QTc interval > 470 ms for females). Subjects with grade III-IV cardiac insufficiency or with left ventricular ejection fraction (LVEF) less than 50% according to NYHA criteria
- Has known history of Human Immunodeficiency Virus (HIV)
- Untreated active hepatitis B
- Subjects have active hepatitis B
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description SBRT/LDRT + Camrelizumab +Apatinib SBRT SBRT（8Gy×3f） LDRT（2Gy×5f） Camrelizumab（200mg，q3w） Apatinib （250mg，qd） SBRT/LDRT + Camrelizumab +Apatinib LDRT SBRT（8Gy×3f） LDRT（2Gy×5f） Camrelizumab（200mg，q3w） Apatinib （250mg，qd） SBRT + docetaxel Docetaxel injection docetaxel 75mg/m2 SBRT（8Gy×3f） SBRT + docetaxel SBRT docetaxel 75mg/m2 SBRT（8Gy×3f） SBRT/LDRT + Camrelizumab +Apatinib Camrelizumab SBRT（8Gy×3f） LDRT（2Gy×5f） Camrelizumab（200mg，q3w） Apatinib （250mg，qd） SBRT/LDRT + Camrelizumab +Apatinib Apatinib SBRT（8Gy×3f） LDRT（2Gy×5f） Camrelizumab（200mg，q3w） Apatinib （250mg，qd）
- Primary Outcome Measures
Name Time Method Objective response rate 6 Weeks Objective Response Rate at 6 months using RECIST1.1 criteria
- Secondary Outcome Measures
Name Time Method Overall Survival 6 Weeks Time from enrollment until death due to any cause
Progression-free Survival 6 Weeks Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause)
Duration Response Rate 6 Weeks ime from the date of the first documented response (CR or PR) to the earliest date of disease progression (RECIST 1.1), or death due to any cause.
incidence, type and severity of adverse events From time of informed consent through treatment period and up to 30 days post last dose of study treatment (about 24 months) Descriptive statistics of safety will be presented using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
Trial Locations
- Locations (1)
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China