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

NCT ID: NCT04878107

Last Updated: 2022-05-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-15
• Study Completion Date: 2023-10-31

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.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SBRT/LDRT + Camrelizumab +Apatinib

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

Group Type: EXPERIMENTAL

Camrelizumab

Intervention Type: DRUG

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

Apatinib

Intervention Type: DRUG

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

SBRT

Intervention Type: RADIATION

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

Intervention Type: RADIATION

low dose radation therapy

SBRT + docetaxel

docetaxel 75mg/m2 SBRT（8Gy×3f）

Group Type: ACTIVE_COMPARATOR

Docetaxel injection

Intervention Type: DRUG

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

SBRT

Intervention Type: RADIATION

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.

Interventions

Camrelizumab

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

Intervention Type: 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

Intervention Type: DRUG

Docetaxel injection

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

Intervention Type: DRUG

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.

Intervention Type: RADIATION

LDRT

low dose radation therapy

Intervention Type: RADIATION

Other Intervention Names

SHR1210

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wuhan University

OTHER

Sponsor Role: lead

Responsible Party

Conghua Xie,MD,PhD

Director of Department of Radiation and Medical Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

CongHua Xie, MD

Role: PRINCIPAL_INVESTIGATOR

Wuhan University

You Lu, MD

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

Site Status: RECRUITING

Countries

China

Central Contacts

CongHua Xie, MD

Role: CONTACT

chxie_65@hotmail.com

02767812510 ext. 86

Facility Contacts

Conghua Xie, Dr

Role: primary

chxie_65@whu.edu.cn

0086-27-67812607

Yu Xu, Dr

Role: backup

xuyu@whu.edu.cn

0086-27-67812607

Other Identifiers

2021061

Identifier Type: -

Identifier Source: org_study_id