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

NCT05979818 | Recruiting Phase 1

• 1 other identifier: XYEYY20230705
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Non Small Cell Lung Cancer; Propranolol

Outcome Measures

Primary Outcomes (3)

• Objective Response Rate (ORR)

  The proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

  2 years

• Disease Control Rate (DCR)

  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)

  2 years

• Adverse events (AEs)

  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

  2 years

Secondary Outcomes (3)

• Progression-free survival (PFS)

  3 years

• Overall survival (OS)

  5 years

• Quality of life (QoL)

  5 years

Study Arms (1)

Propranolol hydrochloride in combination with sintilimab and platinum-based chemotherapy

EXPERIMENTAL

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.

Drug: Propranolol hydrochloride; Drug: Sintilimab; Drug: Chemotherapy

Interventions

Propranolol hydrochloride DRUG

10 mg, PO, BID, for up to 2 years until disease progression/intolerable toxicity/withdrawal of informed consent.

Also known as: Inderal

Propranolol hydrochloride in combination with sintilimab and platinum-based chemotherapy

Sintilimab DRUG

intravenous infusion (IV), 200 mg, Day1, Q3W, for up to 2 years until disease progression/intolerable toxicity/withdrawal of informed consent.

Propranolol hydrochloride in combination with sintilimab and platinum-based chemotherapy

Chemotherapy DRUG

Platinum-based chemotherapy: For non-squamous cell carcinoma options: carboplatin/cisplatin + pemetrexed; For squamous cell carcinoma: carboplatin/cisplatin + paclitaxel/gemcitabine. Carboplatin: IV, AUC 5, Day1, Q3W; Cisplatin: IV, 75 mg/m2, Day1-3, Q3W; Pemetrexed: IV, 500 mg/m2, Day1, Q3W; Paclitaxel: IV, 175 mg/m², Day1, Q3W; Albumin-bound paclitaxel: IV, 100 mg/m², Day1, 8, 15; or 260 mg/m2, Q3W; Gemcitabine: IV, 1000mg/m2, Day1, 8, Q3W; After 4-6 cycles of sintilimab and platinum-based chemotherapy, the patients of non-squamous cell carcinoma will be received with sintilimab and pemetrexed for maintenance therapy, for up to 2 years until disease progression/intolerable toxicity/withdrawal of informed consent.

Propranolol hydrochloride in combination with sintilimab and platinum-based chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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).

Sponsors & Collaborators

• Second Xiangya Hospital of Central South University: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (1)

The Second Xiangya Hospital of Central south University

Changsha, Hunan, 410011, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Propranolol; sintilimab; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Therapeutics

Central Study Contacts

Fang Wu, M.D, Ph.D

CONTACT

+86 13574858332; wufang4461@csu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Associate Professor

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 7, 2023
• Study Start: November 13, 2024
• Primary Completion: August 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 19, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)