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

NCT06670976 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: I-3905123NCI-2024-08858
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Ribonucleic acid sequencing

  Up to 12 weeks

• Changes in immune markers

  Up to 12 weeks

• Catecholamines

  Up to 12 weeks

• Metabolites

  Up to 12 weeks

Study Arms (1)

Treatment (propranolol, RT, surgery)

EXPERIMENTAL

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.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Drug: Propranolol; Radiation: Radiation Therapy; Procedure: Surgical Procedure

Interventions

Biopsy PROCEDURE

Undergo tissue biopsy sample collection

Also known as: BIOPSY_TYPE, Bx

Treatment (propranolol, RT, surgery)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (propranolol, RT, surgery)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (propranolol, RT, surgery)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (propranolol, RT, surgery)

Propranolol DRUG

Given PO

Also known as: 1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol

Treatment (propranolol, RT, surgery)

Radiation Therapy RADIATION

Undergo RT

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (propranolol, RT, surgery)

Surgical Procedure PROCEDURE

Undergo surgery

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Treatment (propranolol, RT, surgery)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Propranolol; Radiotherapy; Radiation; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Therapeutics; Physical Phenomena

Study Officials

• Anurag K Singh

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 1, 2024
• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): November 15, 2029
• Study Completion (Estimated): November 15, 2029
• Last Updated: August 26, 2025

Record last verified: 2025-08

Locations

US (1)