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

Non-Small Cell Lung Cancer Clinical Trial

— SABRE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04878107
• Other study ID #: 2021061
• Status: Recruiting
• Phase: Phase 2
• Start date: March 15, 2022
• Est. completion date: October 2023

Study information

• Verified date: April 2022
• Source: Wuhan University
• Contact: CongHua Xie, MD
• Phone: 02767812510
• Email: chxie_65[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: October 2023
• Est. primary completion date: October 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Camrelizumab
Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd
• Apatinib
Apatinib [Aitan® (brand name in China)], also known as rivoceranib, is a novel, small molecule, selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor
• Docetaxel injection
Docetaxel is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug

Radiation:
• SBRT
Stereotactic body radiation therapy (SBRT) is a cancer treatment that delivers extremely precise, very intense doses of radiation to cancer cells while minimizing damage to healthy tissue. SBRT involves the use of sophisticated image guidance that pinpoints the exact three-dimensional location of a tumor so that the radiation can be more precisely delivered to cancer cells.
• LDRT
low dose radation therapy

Locations

Country	Name	City	State
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate	Objective Response Rate at 6 months using RECIST1.1 criteria	6 Weeks
Secondary	Duration Response Rate	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.	6 Weeks
Secondary	Progression-free Survival	Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause)	6 Weeks
Secondary	Overall Survival	Time from enrollment until death due to any cause	6 Weeks
Secondary	incidence, type and severity of adverse events	Descriptive statistics of safety will be presented using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0	From time of informed consent through treatment period and up to 30 days post last dose of study treatment (about 24 months)