Clinical trial NCT04878107: 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
Official title: 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：a Prospective Exploratory Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: stereotactic body radiotherapy
Low-Dose Radiation Therapy
Camrelizumab
Apatinib
Lead sponsor: Wuhan University
Sponsor class: OTHER
First posted: 2021-05-07
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Objective response rate
timeFrame: 6 Weeks
Secondary outcomes:
measure: Duration Response Rate
timeFrame: 6 Weeks
measure: Progression-free Survival
timeFrame: 6 Weeks
measure: Overall Survival
timeFrame: 6 Weeks
measure: incidence, type and severity of adverse events
timeFrame: From time of informed consent through treatment period and up to 30 days post last dose of study treatment (about 24 months)
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
Study officials:
affiliation: Wuhan University
name: CongHua Xie, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: West China Hospital
name: You Lu, MD
role: PRINCIPAL_INVESTIGATOR
References: