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

12 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment Propranolol + Radiation Therapy for Soft Tissue Sarcoma?

Research shows that combining different types of radiation therapy, like intraoperative radiotherapy, with surgery can improve long-term outcomes for soft tissue sarcoma by reducing the chance of the cancer coming back. While propranolol is not directly mentioned, the combination of treatments is a common strategy to enhance effectiveness. ^{1 2 3 4 5}

Is the combination of propranolol and radiation therapy generally safe for humans?

Propranolol, a medication often used for heart conditions, has been studied for its potential to enhance cancer treatments, including radiation therapy. While specific safety data for the combination with radiation therapy in soft tissue sarcoma is limited, propranolol has been used safely in humans for various conditions, and studies suggest it may help improve the effectiveness of cancer treatments. ^{6 7 8 9 10}

How does the drug Propranolol combined with radiation therapy differ from other treatments for soft tissue sarcoma?

Propranolol, a drug typically used for heart conditions, is being explored in combination with radiation therapy for soft tissue sarcoma, which is unique because it may enhance the effects of radiation by targeting blood vessels in the tumor, potentially improving treatment outcomes compared to radiation alone. ^{1 2 11 12 13}

Research Team

Anurag K. Singh

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

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

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

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

Known hypersensitivity to propranolol

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Intraoperative radiotherapy for primary and locally recurrent soft tissue sarcoma: morbidity and long-term prognosis. [2007]

2. England pubmed.ncbi.nlm.nih.gov

Radiotherapy and hyperthermia with curative intent in recurrent high risk soft tissue sarcomas. [2019]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Long-term results of combined treatment of soft tissue sarcoma with the use of intraoperative radiotherapy]. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

The role of hyperthermia in combined treatment in the management of soft tissue sarcoma. [2019]

5. England pubmed.ncbi.nlm.nih.gov

High-risk soft tissue sarcoma: clinical trial and hyperthermia combined chemotherapy. [2007]

6. New Zealand pubmed.ncbi.nlm.nih.gov

The role of propranolol as a radiosensitizer in gastric cancer treatment. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

The adrenergic receptor antagonists propranolol and carvedilol decrease bone sarcoma cell viability and sustained carvedilol reduces clonogenic survival and increases radiosensitivity in canine osteosarcoma cells. [2020]

9. England pubmed.ncbi.nlm.nih.gov

The β-adrenergic receptor antagonist propranolol offsets resistance mechanisms to chemotherapeutics in diverse sarcoma subtypes: a pilot study. [2021]

10. Canada pubmed.ncbi.nlm.nih.gov

In vitro sensitivity of leukemia cells to propranolol. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

[Intraoperative radiotherapy as part of the treatment concept of soft tissue sarcomas]. [2019]

12. Pakistan pubmed.ncbi.nlm.nih.gov

Radiotherapy alone with concurrent chemoradiotherapy plus temozolamide in locally advanced soft tissue sarcoma at Mayo Hospital Lahore: A randomized controlled trial. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Postirradiation soft tissue sarcoma occurring in breast cancer patients: report of seven cases and results of combination chemotherapy. [2019]