Propranolol for Kaposi Sarcoma

Recruiting at 2 trial locations

Overseen By Lee Ratner, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Antiretroviral therapy

Must not be taking: Beta blockers, Anticancer therapies

Disqualifiers: Asthma, Diabetes, Heart failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 22 weeks

25 Participants Needed

Trial Summary

What is the purpose of this trial?

Kaposi sarcoma (KS) lesions are initiated by endothelial cells infected with KS herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). Lesion progression is driven by abnormal angiogenesis, chronic inflammation, and uncontrolled cell proliferation. KS remains one of the most commonly diagnosed cancers in many African countries where economic constraints prevent successful treatment in most patients. Treatment outcomes in developed countries are also often unsatisfactory in HIV positive patients despite good virological and immunological responses to antiretroviral therapy. Therefore, identification of new oral, safe treatment options for treatment of KS remains a research priority. Given the known anti-angiogenic properties and based on the treatment response with other benign vascular lesions such as infantile hemangioma, propranolol is a good candidate for the treatment of KS. The hypothesis of this study is that treating patients with Kaposi sarcoma with propranolol will result in an overall response rate (complete response rate plus partial response rate) of at least 45%, and that propranolol will be safe and well tolerated in this patient population.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking any beta-blockers (a type of medication often used for heart conditions) and any anticancer therapies at least 4 weeks before starting propranolol. If you are on antiretroviral therapy for HIV, you must continue it as per local standards.

What data supports the effectiveness of the drug Propranolol for treating Kaposi Sarcoma?

There is no direct evidence from the provided research articles supporting the effectiveness of Propranolol for treating Kaposi Sarcoma. However, Timolol, a similar type of drug, has shown promise in treating Kaposi Sarcoma in some cases, suggesting that drugs in this category might have potential, but more studies are needed. ^{1 2 3 4 5}

How is the drug Propranolol unique in treating Kaposi Sarcoma?

Propranolol is unique in treating Kaposi Sarcoma because it is a beta-blocker (a type of drug that reduces blood pressure) typically used for heart conditions, but it is being explored for its potential to treat this cancer, which currently lacks a well-defined standard treatment. ^{2 3 4 6 7}

Research Team

Lee Ratner, MD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with Kaposi Sarcoma, a cancer caused by the KS herpesvirus. It's looking for participants who need new treatment options, including those in countries with limited access to current treatments or HIV positive patients not responding well despite antiretroviral therapy.

Inclusion Criteria

I can swallow pills.

My Kaposi's sarcoma has worsened on ART after 12-24 weeks, needing more treatment.

I weigh more than 40 kg.

Exclusion Criteria

I have asthma or another obstructive airway disease.

I have hepatitis C that is either not cured or still detectable.

I don't have another cancer that could affect this treatment's study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants begin at 1/2 the target dose for 7 days, followed by a tolerability assessment. If tolerated, they continue with the full/target dose for 7 days, then the target dose for 12 weeks. Depending on response, treatment may continue for an additional 8 weeks.

22 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Propranolol

Trial Overview The study tests Propranolol Hydrochloride, known for blocking blood vessel growth and inflammation. The goal is to see if it can treat Kaposi Sarcoma effectively. Researchers hope at least 45% of patients will show major improvement.

Participant Groups

Group I: Propranolol Experimental Treatment 1 Intervention

Begin at 1/2 the target dose for 7 days (14 doses), followed by a tolerability assessment. Patients who tolerate the 1/2 dose will begin the full/target dose for 7 days (14 doses), after which tolerability will be assessed. Patients who do not tolerate the full/target dose will decrease to a 1/2 dose for 2 days and then discontinue treatment; these patients will be withdrawn from the study and replaced. Those who continue will take the target dose for 12 weeks. At 12-week time point, one of the following paths will be taken: * Complete response or partial response: continue taking propranolol at the target dose for another 8 weeks, followed by a reduced dose (1/2 the target) for 7 days, then discontinue treatment * No response (stable disease/disease progression):reduced dose (1/2 the target) for 7 days, then discontinue treatment

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?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

References

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

Timing of highly active antiretroviral therapy and chemotherapy for Kaposi's sarcoma in patients with HIV infection. [2013]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Oral etoposide for Kaposi's Mediterranean sarcoma. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Intralesional chemotherapy for Kaposi's sarcoma. [2019]

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

Failed Treatment of Classic Kaposi's Sarcoma with Topical Timolol: Case Report and Review of the Literature. [2020]

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

Impact of highly active antiretroviral therapy on the presenting features and outcome of patients with acquired immunodeficiency syndrome-related Kaposi sarcoma. [2006]

6. Australia pubmed.ncbi.nlm.nih.gov

Allergic contact dermatitis caused by timolol eyedrop application for classic Kaposi sarcoma. [2021]

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

Phase II evaluation of low-dose oral etoposide for the treatment of relapsed or progressive AIDS-related Kaposi's sarcoma: an AIDS Clinical Trials Group clinical study. [2016]