Propranolol Hydrochloride in Combination With Sintilimab and Platinum-based Chemotherapy for Treatment of Advanced Non-small Cell Lung Cancer

Recruiting now · Phase 1

Conditions studied: Non Small Cell Lung Cancer, Propranolol

In brief

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.

Key facts

Study ID

NCT05979818

Run by

Second Xiangya Hospital of Central South University

People needed

6

Starts

2024-11-13

Expected to finish

2026-12-31

Last updated by the study team

2024-11-19

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• No CNS symptoms or no worsening of symptoms for at least 2 weeks.
• No glucocorticoid therapy is required, or glucocorticoid therapy has been discontinued within 7 days prior to the first dose, or the glucocorticoid dosage has been stable and reduced to less than 10 mg/day of prednisone (or equivalent dose) within 7 days prior to the first dose
• Meet the following laboratory indicators (within 14 days before the first treatment):
• Blood routine examination: absolute neutrophil count ≥ 1.5 x 10\^9/L; platelet count ≥ 100 x 10\^9/L; hemoglobin level ≥ 9.0 g/dL (no blood transfusion or erythropoietin-dependent administration within 7 days).
• Liver function: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN in the absence of hepatic metastases; ALT or AST ≤ 5 × ULN in the case of patients with hepatic metastases.
• Renal function: serum creatinine (Cr) ≤1.5 times ULN or Cr clearance ≥60 mL/min (Cockcroft-Gault formula), and urine routine test results show urine protein (UPRO) <2+ or 24-hour urine protein quantification <1g.
• Coagulation: International Normalized Ratio (INR) ≤ 1.5 times ULN or Prothrombin Time (PT) ≤ 1.5 times ULN within 7 days prior to study treatment; if the subject is receiving anticoagulant therapy, as long as the PT is within the range of the anticoagulant drug
• Heart function: the New York heart association (NYHA) classification < 3;Left ventricular ejection fraction（LVEF）≥ 50%; Baseline ECG showed no PR interval lengthened or atrioventricular block
• For female subjects of childbearing potential, a negative urine or serum pregnancy test should be obtained within 3 days prior to receiving the first dose of study drug (Day 1 of Cycle 1). If a negative urine pregnancy test result cannot be confirmed, a blood pregnancy test will be requested. Females not of childbearing potential are defined as being at least 1 year postmenopausal or having undergone surgical sterilization or hysterectomy; if conception is at risk, all subjects (male or female) are required to use contraception with an annual failure rate of less than 1% throughout the treatment period up to 120 days after the end-of-treatment administration of study drug (or 180 days after the end-of-study drug administration)

You may not qualify if…

• 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
• Right heart insufficiency due to pulmonary hypertension.
• Congestive heart failure (class III or IV).
• Hypotension (systolic blood pressure < 100 mmHg).
• Prolonged fasting.
• Severe peripheral circulatory failure (e.g., gangrene).
• Symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma.
• Unstable angina or variant angina.
• Patients on rizatriptan benzoate.
• Severe asthma or chronic obstructive pulmonary disease (COPD)
• Uncontrolled type I or type II diabetes mellitus (glycosylated hemoglobin [HbA1C] > 8.5 or fasting blood glucose > 160 mg/dl at screening).
• Current use or within the last 2 years of a non-dihydropyridine calcium channel blocker (NDCCB)
• Hepatic encephalopathy, hepatorenal syndrome or Child-Pugh class B or more severe cirrhosis
• Tumor-related intestinal obstruction (within 3 months prior to the signing of the informed consent) or history of inflammatory bowel disease or extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis
• Completion of palliative radiotherapy within 7 days prior to the first dose of study drug
• With clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction

Where it is running

• The Second Xiangya Hospital of Central south University — Changsha, Hunan, China (enrolling)

Full record on ClinicalTrials.gov

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