Propranolol Plus Standard Radiation Therapy Before Surgery for the Treatment of Patients With Soft Tissue Sarcoma

Pilot Study of Soft Tissue Sarcoma Treated With Propranolol and Radiation

This phase I trial tests the safety, tolerability and impact of adding propranolol to standard radiation therapy (RT) before surgery for the treatment of patients with soft tissue sarcoma. Sarcomas are a diverse group of rare tumors arising from connective tissue. Approximately 13,000-16,000 new cases of sarcomas arise in the United States annually. Sarcoma management involves multidisciplinary team decision making and treatment is multimodal utilizing chemotherapy (if needed) and RT prior to surgical intervention. Propranolol is a drug that has been used for many years for high blood pressure by blocking both beta-1 and beta-2 adrenergic receptors. Preclinical data suggests that blocking the beta-2 adrenergic receptors can improve the response to both chemotherapy and radiation. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. RT before surgery makes the tumor smaller and reduces the amount of tissue that needs to be removed during surgery. Surgery is the most common treatment for soft tissue sarcoma. Giving propranolol with standard RT before surgery may be safe, tolerable and impactful in treating patients with soft tissue carcinoma.

Study Overview

• Status: Withdrawn
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Radiation: Radiation Therapy; Procedure: Biospecimen Collection; Procedure: Surgical Procedure; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Drug: Propranolol; Procedure: Biopsy

Detailed Description

PRIMARY OBJECTIVE:

I. To establish the safety and tolerability of adding propranolol to standard RT for soft tissue sarcoma.

SECONDARY OBJECTIVE:

I. To evaluate the response of tumor immune microenvironment to treatments for patients.

OUTLINE:

Patients receive propranolol orally (PO) twice daily (BID) for 2 weeks prior to standard of care RT (weeks 1 and 2) and then during and after standard of care RT (weeks 3-7). Treatment continues in the absence of disease progression or unacceptable toxicity until the time of standard of care surgery (week 8). Additionally, patients undergo positron emission tomography (PET) scan and/or computed tomography (CT) scan during screening and may undergo blood and tissue biopsy sample collection throughout the trial.

After completion of study treatment, patients are followed up at 5 weeks.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years old
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
• Eligible for curative-intent radiation therapy for a soft tissue extremity sarcoma
• Ability to swallow and retain oral medication
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Known hypersensitivity to propranolol
• Contraindication to beta-blockers e.g.; uncontrolled depression, unstable angina pectoris, uncontrolled heart failure (New York Heart Association [NYHA] grade III or IV), hypotension (systolic blood pressure < 85 or fasting plasma glucose > 160 mg/dL at screening), symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma, current nondihydropyridines calcium channel blocker use (such as verapamil, diltiazem) or rhythm control agents such as digoxin and amiodarone. Patients with pacemakers will be excluded
• Patients cannot be on propranolol and another beta-blocker simultaneously. Patients already on beta-blockers can (with approval and under supervision of their primary care physician and/or cardiologist) may choose to stop their current beta-blocker and switch to propranolol for the duration of the study
• Pregnant or nursing female participants
• Unwilling or unable to follow protocol requirements
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (propranolol, RT, surgery); Patients receive propranolol PO BID for 2 weeks prior to standard of care RT (weeks 1 and 2) and then during and after standard of care RT (weeks 3-7). Treatment continues in the absence of disease progression or unacceptable toxicity until the time of standard of care surgery (week 8). Additionally, patients undergo PET scan and/or CT scan during screening and may undergo blood and tissue biopsy sample collection throughout the trial.

Radiation: Radiation Therapy; Undergo RT; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Surgical Procedure; Undergo surgery; Other Names: Operation; Surgery; Surgery Type; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery; Surgery, NOS; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Drug: Propranolol; Given PO; Other Names: 1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol; Procedure: Biopsy; Undergo tissue biopsy sample collection; Other Names: Bx; BIOPSY_TYPE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Will evaluate safety and tolerability of adding propranolol to standard radiation therapy for soft tissue sarcoma. Will determine the occurrence of a grade 3 or higher treatment related adverse events. Will summarize using frequencies and relative frequencies, with the grade 3 or higher toxicity rate estimated using a 90% credible region obtained by Jeffrey's prior method. Will summarize toxicities and adverse events (as per Common Terminology Criteria for Adverse Events version 5.0) by attribution and grade using frequencies and relative frequencies.	Up to 5 weeks post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ribonucleic acid sequencing	Will evaluate with biopsy specimens. Will summarize using the mean and standard deviation, and graphically using line and mean plots. Will be modeled as a function of time and a random patient effect using linear mixed models. Tests about the appropriate contrast of model estimates will be used to evaluate changes over time. All model assumptions will be verified graphically and transformations applied as appropriate.	Up to 12 weeks
Changes in immune markers	Changes in immune markers of CD8+ and CD4+ T cells and polymorphonuclear-myeloid-derived suppressor cells will be determined by flow cytometry in peripheral blood. Will summarize using the mean and standard deviation, and graphically using line and mean plots. Will be modeled as a function of time and a random patient effect using linear mixed models. Tests about the appropriate contrast of model estimates will be used to evaluate changes over time. All model assumptions will be verified graphically and transformations applied as appropriate.	Up to 12 weeks
Catecholamines	Will correlate the levels of catecholamines and metabolites in peripheral blood. Will summarize using the mean and standard deviation, and graphically using line and mean plots. Will be modeled as a function of time and a random patient effect using linear mixed models. Tests about the appropriate contrast of model estimates will be used to evaluate changes over time. All model assumptions will be verified graphically and transformations applied as appropriate.	Up to 12 weeks
Metabolites	Will correlate the levels of catecholamines and metabolites in peripheral blood. Will summarize using the mean and standard deviation, and graphically using line and mean plots. Will be modeled as a function of time and a random patient effect using linear mixed models. Tests about the appropriate contrast of model estimates will be used to evaluate changes over time. All model assumptions will be verified graphically and transformations applied as appropriate.	Up to 12 weeks

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Anurag K Singh, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): November 15, 2029
• Study Completion (Estimated): November 15, 2029

Study Registration Dates

• First Submitted: October 31, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Actual): November 1, 2024

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma; Organic Chemicals; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytological Techniques; Cytodiagnosis; Hydrocarbons; Hydrocarbons, Cyclic; Physical Phenomena; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Amines; Diagnostic Techniques, Surgical; Alcohols; Chemistry Techniques, Analytical; Spectrum Analysis; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Electromagnetic Phenomena; Magnetic Phenomena; Propranolol; Radiotherapy; Radiation; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Electromagnetic Radiation; Surgical Procedures, Operative
• Other Study ID Numbers: I-3905123 (Other Identifier: Roswell Park Cancer Institute); NCI-2024-08858 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes