Study of Propranolol Hydrochloride in Combination With Sintilimab and Platinum-based Chemotherapy for Treatment of Advanced Non-small Cell Lung Cancer (BRIO)
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Second Xiangya Hospital of Central South University
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR)
Overview
Brief Summary
This study is a prospective single-center Phase I clinical study in patients with EGFR/ALK/ROS1 driver oncogene negative, and advanced or metastatic NSCLC. This study is to evaluate the efficacy and safety preliminarily in a small-size of propranolol hydrochloride in combination with sintilimab and platinum-based chemotherapy in first-line therapy. Propranolol hydrochloride is a beta- adrenergic blocking agent which is associated with augment of immune cell responses. Propranolol hydrochloride may improve the responses of immune checkpoint inhibitors in treating patients with advanced NSCLC.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Sign a written informed consent prior to any research-related procedure
- •Age ≥18 years and ≤ 75 years old
- •ECOG PS score of 0-1
- •Expected survival time ≥ 12 weeks
- •Patients with histologically or cytologically confirmed non-localizable stage IIIB-IIIC, stage IV non-small cell lung cancer (International Association for the Study of Lung Cancer and the Joint Committee on the American Classification of Cancers, 8th edition). Patients with unresectable IIIB-IIIC include recurrent and primary unresectable (surgery and radical concurrent chemoradiotherapy), and stage IV includes primary or recurrent stage IV but without prior systemic therapy for advanced/metastatic disease.
- •Chemotherapy and chemoradiotherapy are permitted as neoadjuvant/adjuvant treatment as long as the treatment is completed at least 12 months prior to the diagnosis of advanced or metastatic disease
- •There must be no EGFR gene-sensitive mutation, ALK gene fusion or ROS1 gene fusion in non-squamous carcinoma
- •At least one imaging measurable lesion according to the criteria for the evaluation of the efficacy of solid tumors (RECIST version 1.1). A lesion located in the field of exposure to previous radiotherapy is considered measurable if progression is confirmed (within 28 days prior to the first treatment)
- •Subjects with brain metastases who are asymptomatic or whose symptoms have stabilized with local treatment are permitted to be enrolled, provided that the subject meets the following criteria:
- •Have a measurable lesion outside the CNS.
Exclusion Criteria
- •Concurrent participation in another interventional clinical study or receipt of another investigational drug, unless participating in an observational clinical study
- •Prior exposure to any anti-PD-1 or anti-PD-L1, PD-L2, CD137, CTLA-4 antibody therapy, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- •Systemic therapy with proprietary Chinese medicines with anti-tumor indications or immunomodulatory drugs (including thiopeptides, interferons, interleukins, except those used locally for the control of hydrothorax or ascites) within 2 weeks prior to the first dose
- •Current use of oral or intravenous beta-blockers (e.g., atenolol, bisoprolol, carvedilol, labetalol, metoprolol, nadolol, sotalol, etc.) cannot be safely switched to a non-beta-blocker
- •There are contraindications to the use of beta-blockers:
- •Hypersensitivity to any of the components of the product.
- •Bronchial asthma or risk of bronchospasm.
- •Ketoacidosis and metabolic acidosis.
- •Severe or symptomatic bradycardia (resting heart rate ≤55bpm), atrioventricular block (degrees II and III), sinus block, sick sinus node syndrome.
- •Cardiogenic shock
Arms & Interventions
Propranolol hydrochloride in combination with sintilimab and platinum-based chemotherapy
Patients receive propranolol hydrochloride PO BID, pembrolizumab IV over 30 minutes of day 1 and chemotherapy IV. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: Propranolol hydrochloride (Drug)
Propranolol hydrochloride in combination with sintilimab and platinum-based chemotherapy
Patients receive propranolol hydrochloride PO BID, pembrolizumab IV over 30 minutes of day 1 and chemotherapy IV. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: Sintilimab (Drug)
Propranolol hydrochloride in combination with sintilimab and platinum-based chemotherapy
Patients receive propranolol hydrochloride PO BID, pembrolizumab IV over 30 minutes of day 1 and chemotherapy IV. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: Chemotherapy (Drug)
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: 2 years
The proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Disease Control Rate (DCR)
Time Frame: 2 years
Disease Control Rate (DCR) The proportion of patients with a complete response or partial response or stable disease to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Adverse events (AEs)
Time Frame: 2 years
Based on the physical examination, vital signs, laboratory findings, and medical examinations, and record the type, incidence, severity of AEs, which were graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Secondary Outcomes
- Overall survival (OS)(5 years)
- Progression-free survival (PFS)(3 years)
- Quality of life (QoL)(5 years)
Investigators
Fang Wu
Chief Physician, Associate Professor
Second Xiangya Hospital of Central South University