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

NCT ID: NCT06670976

Last Updated: 2025-08-26

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-05-15
• Study Completion Date: 2029-11-15

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.

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.

Conditions

Soft Tissue Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Biopsy

Intervention Type: PROCEDURE

Undergo tissue biopsy sample collection

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT scan

Positron Emission Tomography

Intervention Type: PROCEDURE

Undergo PET scan

Propranolol

Intervention Type: DRUG

Given PO

Radiation Therapy

Intervention Type: RADIATION

Undergo RT

Surgical Procedure

Intervention Type: PROCEDURE

Undergo surgery

Interventions

Biopsy

Undergo tissue biopsy sample collection

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Computed Tomography

Undergo CT scan

Intervention Type: PROCEDURE

Positron Emission Tomography

Undergo PET scan

Intervention Type: PROCEDURE

Propranolol

Given PO

Intervention Type: DRUG

Radiation Therapy

Undergo RT

Intervention Type: RADIATION

Surgical Procedure

Undergo surgery

Intervention Type: PROCEDURE

Other Intervention Names

BIOPSY_TYPE; Bx; Biological Sample Collection; Biospecimen Collected; Specimen Collection; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; Computerized Tomography (CT) scan; CT; CT Scan; tomography; 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; 1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol; Cancer Radiotherapy; Energy Type; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Operation; Surgery; Surgery Type; Surgery, NOS; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anurag K Singh

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Countries

United States

Other Identifiers

NCI-2024-08858

Identifier Type: REGISTRY

Identifier Source: secondary_id

I-3905123

Identifier Type: OTHER

Identifier Source: secondary_id

I-3905123

Identifier Type: -

Identifier Source: org_study_id