SABRE: 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

Sponsor

Wuhan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04878107

Collaborator

(none)

Enrollment

Location

Arms

18.6

Anticipated Duration (Months)

4.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: Camrelizumab Drug: Apatinib Drug: Docetaxel injection Radiation: SBRT Radiation: LDRT	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

88 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 15, 2022

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SBRT/LDRT + Camrelizumab +Apatinib SBRT（8Gy×3f） LDRT（2Gy×5f） Camrelizumab（200mg，q3w） Apatinib （250mg，qd）	Drug: Camrelizumab Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd Other Names: SHR1210 Drug: 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 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. Radiation: LDRT low dose radation therapy
Active Comparator: SBRT + docetaxel docetaxel 75mg/m2 SBRT（8Gy×3f）	Drug: 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.

Arm

Intervention/Treatment

Experimental: SBRT/LDRT + Camrelizumab +Apatinib

SBRT（8Gy×3f） LDRT（2Gy×5f） Camrelizumab（200mg，q3w） Apatinib （250mg，qd）

Drug: Camrelizumab

Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd

Other Names:

SHR1210

Drug: 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

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.

Radiation: LDRT

low dose radation therapy

Active Comparator: SBRT + docetaxel

docetaxel 75mg/m2 SBRT（8Gy×3f）

Drug: Docetaxel injection

Docetaxel is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug

Radiation: SBRT

Outcome Measures

Primary Outcome Measures

Objective response rate [6 Weeks]
Objective Response Rate at 6 months using RECIST1.1 criteria

Secondary Outcome Measures

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.
Progression-free Survival [6 Weeks]
Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause)
Overall Survival [6 Weeks]
Time from enrollment until 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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