Propranolol Plus Standard Radiation Therapy Before Surgery for the Treatment of Patients With Soft Tissue Sarcoma
August 19, 2025 updated by: Roswell Park Cancer Institute
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Withdrawn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
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
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
New York
-
Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
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.
|
Undergo RT
Other Names:
Undergo blood sample collection
Other Names:
Undergo surgery
Other Names:
Undergo PET scan
Other Names:
Undergo CT scan
Other Names:
Given PO
Other Names:
Undergo tissue biopsy sample collection
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of adverse events
Time Frame: Up to 5 weeks post-surgery
|
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
Time Frame: Up to 12 weeks
|
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
Time Frame: Up to 12 weeks
|
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
Time Frame: Up to 12 weeks
|
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
Time Frame: Up to 12 weeks
|
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
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Anurag K Singh, Roswell Park Cancer Institute
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.