Propranolol + Radiation Therapy for Soft Tissue Sarcoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must be taking: Propranolol

Must not be taking: Nondihydropyridines, Digoxin, Amiodarone

Disqualifiers: Uncontrolled illness, Hypersensitivity, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether adding propranolol, a drug typically used for high blood pressure, to standard radiation therapy can safely enhance treatment for soft tissue sarcoma, a cancer that forms in connective tissues. The goal is to determine if propranolol can shrink tumors more effectively before surgery. This approach may suit adults already scheduled for radiation therapy to treat a sarcoma in their limbs and who can take oral medication. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but if you are on a beta-blocker, you may need to switch to propranolol for the study. This should be done with approval and supervision from your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that propranolol, when combined with standard radiation therapy before surgery, might be safe and manageable for treating soft tissue sarcoma. Propranolol has been used for many years to treat high blood pressure, providing extensive knowledge about its safety. Some studies have tested propranolol with other cancer treatments and found it to be generally well-tolerated. While side effects can occur, such as increased risk when combined with certain medications, proper care can manage these. This trial is in an early stage, focusing on the safety and tolerability of propranolol with radiation. Since propranolol is already approved for other uses, its safety under medical supervision is well-supported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for soft tissue sarcoma?

Researchers are excited about using propranolol combined with radiation therapy for soft tissue sarcoma because it introduces a unique approach to treatment. Unlike standard chemotherapy or radiation alone, propranolol, a beta-blocker, may enhance the effectiveness of radiation by limiting tumor blood flow and reducing hypoxia, making cancer cells more susceptible to treatment. This combination could lead to better tumor control without significantly increasing toxicity, potentially improving outcomes for patients with this challenging condition.

What evidence suggests that propranolol combined with radiation therapy might be an effective treatment for soft tissue sarcoma?

Research has shown that propranolol, a beta blocker, might enhance the effectiveness of cancer treatments. It slows the growth of sarcomas, cancers originating in the body's connective tissues. Propranolol blocks certain signals that cancer cells use to grow and spread, potentially making treatments like radiation therapy more effective. In this trial, participants will receive propranolol alongside standard radiation therapy. Lab studies have demonstrated better results when propranolol is used with other cancer-fighting drugs. Although more research is needed, these findings suggest that propranolol could be a promising addition to sarcoma treatment plans. ^{3 5 6 7 8}

Who Is on the Research Team?

Anurag K. Singh

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with soft tissue sarcoma who are preparing to undergo surgery. It's designed to test if adding a blood pressure medication, propranolol, to standard radiation therapy before surgery can be safe and improve treatment outcomes.

Inclusion Criteria

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

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

I can perform daily activities with minimal assistance.

Exclusion Criteria

Known hypersensitivity to propranolol

Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

I am not taking propranolol and another beta-blocker at the same time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Propranolol Treatment

Participants receive propranolol orally twice daily for 2 weeks prior to standard of care radiation therapy

2 weeks

Daily medication administration

Radiation Therapy

Participants receive standard of care radiation therapy while continuing propranolol treatment

5 weeks

Regular radiation sessions

Surgery

Standard of care surgery is performed after completion of radiation therapy

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Propranolol
• Standard Radiation Therapy

Trial Overview The study is examining the safety and effects of combining propranolol with standard radiation therapy prior to surgical removal of the tumor in soft tissue sarcoma patients. The goal is to see if this combination makes tumors smaller and enhances patient response.

How Is the Trial Designed?

Group I: Treatment (propranolol, RT, surgery) Experimental Treatment 7 Interventions

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.

Propranolol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Inderal for:

• High blood pressure
• Angina pectoris
• Heart rhythm disorders
• Migraine prophylaxis
• Essential tremor
• Performance anxiety

Approved in European Union as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Approved in Canada as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

Long-acting propranolol (Inderal LA) provides a controlled release of the medication, maintaining higher plasma concentrations over 24 hours compared to conventional tablets, which helps ensure consistent beta-adrenoceptor blockade.

This formulation is equally effective for treating conditions like angina pectoris, hypertension, and hyperthyroidism, while potentially improving patient adherence to treatment due to simplified dosing regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use. Mishriki, AA., Weidler, DJ.[2019]

In a study involving 64 male nude mice with gastric cancer, propranolol was found to enhance the effectiveness of radiotherapy, resulting in reduced tumor growth compared to other treatment groups.

The combination of propranolol and radiation therapy led to decreased expression of NF-κB and its downstream targets (COX-2, EGFR, and VEGF), suggesting a mechanism by which propranolol acts as a radiosensitizer in gastric cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of propranolol as a radiosensitizer in gastric cancer treatment. Liao, X., Chaudhary, P., Qiu, G., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5978448/

Non-selective beta blockers inhibit angiosarcoma cell ... These data suggest that incorporation of non-selective β-AR antagonists into existing therapies against metastatic angiosarcoma can enhance clinical outcomes.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05961761

Propranolol and Pembrolizumab in Advanced Soft Tissue ... The goal of this phase 2 clinical trial is to test efficacy and tolerability of combining propranolol and pembrolizumab in patients with advanced ...

3. biorxiv.org biorxiv.org/content/10.1101/2021.03.11.434711v1.full-text

Propranolol reduces sarcoma growth and enhances the ... Our results identify propranolol as an immune modulating agent, which can improve immune checkpoint inhibitor therapies in soft tissue sarcoma ...

4. sigma.larvol.com sigma.larvol.com/ott.php?e1=5068&e2=&sourcepg=TZ&sr=now&er=1+month&ipwnd=on&rlink=,sourcepg=TZ,itype=0,1&rflag=1&page=2

Online Trial Tracker PROPANE, NCT05961761: Propranolol and Pembrolizumab in Advanced Soft Tissue Sarcoma Patients. Recruiting. 2. 80. Europe. Propranolol, Betablocker, Pembrolizumab ...

5. go.drugbank.com go.drugbank.com/drugs/DB00571

Propranolol: Uses, Interactions, Mechanism of Action Propranolol is a non-selective beta adrenergic antagonist used to treat hypertension, angina, atrial fibrillation, myocardial infarction, migraine, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06670976

Propranolol Plus Standard Radiation Therapy Before ... Giving propranolol with standard RT before surgery may be safe, tolerable and impactful in treating patients with soft tissue carcinoma. Detailed Description.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12541171/

Efficacy and safety of vascular-targeting agents in advanced ... Efficacy and safety of vascular-targeting agents in advanced soft tissue sarcoma: a systematic review and network meta-analysis - PMC.

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-08858

Propranolol Plus Standard Radiation Therapy before ... Surgery is the most common treatment for soft tissue sarcoma. Giving propranolol with standard RT before surgery may be safe, tolerable and impactful in ...