Pazopanib for Hereditary Hemorrhagic Telangiectasia

(Paz Trial)

Not currently recruiting at 12 trial locations

Overseen By Cassi Friday, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Cure HHT

Must not be taking: VEGF inhibitors, Bevacizumab

Disqualifiers: Cerebral AVMs, Pulmonary AVMs, Recent malignancies, Heart disease, others

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: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a daily dose of Pazopanib (also known as Votrient or pazopanib hydrochloride) can reduce nosebleeds in individuals with hereditary hemorrhagic telangiectasia (HHT), a condition causing frequent bleeding and anemia. Participants will receive either the drug or a placebo and will be monitored for nosebleed severity and blood loss over 24 weeks. Suitable candidates have a confirmed or probable diagnosis of HHT, experience frequent nosebleeds, and require regular iron treatments or blood transfusions. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications that are on a prohibited list for at least 14 days or 5 half-lives of the drug (whichever is longer) before starting the study and for the duration of the study. However, the specific medications on this list are not detailed in the provided information.

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

The trial requires participants to stop using certain medications that are on a prohibited list at least 14 days before starting the study and for the duration of the study. However, the specific medications on this list are not detailed in the provided information.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that most people tolerate pazopanib well. Previous studies identified common side effects such as fatigue, diarrhea, and changes in hair color, while serious side effects were less common. The FDA has already approved pazopanib for other uses, which supports its safety profile. However, since reactions to medications can vary, monitoring for any new symptoms is crucial. Always consult a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for HHT?

Pazopanib is unique because it targets hereditary hemorrhagic telangiectasia (HHT) by inhibiting specific proteins called tyrosine kinases, which are involved in the formation of abnormal blood vessels. Unlike traditional treatments for HHT, which often focus on managing symptoms like bleeding, pazopanib aims to address the underlying vascular issues. Researchers are excited about this treatment because it offers a potential way to reduce the frequency and severity of bleeding episodes, a major issue for patients with this condition. Additionally, its oral administration makes it convenient for patients, potentially improving adherence and quality of life.

What evidence suggests that Pazopanib might be an effective treatment for hereditary hemorrhagic telangiectasia?

Research has shown that Pazopanib might help reduce bleeding in people with hereditary hemorrhagic telangiectasia (HHT). Studies have found that it can decrease the frequency of nosebleeds, a common symptom of HHT. Pazopanib blocks certain signals in the body that cause bleeding. In this trial, participants will receive either Pazopanib or a placebo to evaluate its effectiveness. In some cases, Pazopanib has helped patients with severe, ongoing bleeding that does not improve with other treatments. While these results are promising, further research is needed to confirm its effectiveness for everyone with HHT. ^{1 2 3 5 6}

Who Is on the Research Team?

James R Gossage, MD

Principal Investigator

Augusta University

Are You a Good Fit for This Trial?

This trial is for individuals with hereditary hemorrhagic telangiectasia (HHT) who experience severe nosebleeds and anemia. Participants must be able to monitor their blood pressure at home, not start new HHT therapies during the study, and women of childbearing age must use effective contraception. People with certain medical conditions or on prohibited medications cannot join.

Inclusion Criteria

Women of childbearing potential must agree to abstinence or to use an acceptable double method contraception until 4 weeks after drug termination with pregnancy testing throughout the trial

I have been diagnosed with hereditary hemorrhagic telangiectasia.

I agree not to have nasal vein treatments or start new HHT therapies while in the study.

Exclusion Criteria

I am taking medication that can affect my heart's rhythm.

Inability or unwillingness to discontinue prohibited medications

Recent participation in a clinical trial with investigational product

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part B

Participants receive either 150 mg Pazopanib or placebo daily for 24 weeks to assess effects on nose bleed severity and anemia

24 weeks

Visits every 3 weeks for dosing intervals

Extension Study Part C

Participants who complete Part B may continue with active drug for an additional 24 weeks to further assess effects on nose bleeds and safety

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pazopanib
• Placebo oral capsule

Trial Overview

The trial tests if Pazopanib can reduce nosebleed severity in HHT patients over a 24-week period compared to a placebo. It also monitors blood loss and safety. Patients will take the drug daily and have regular check-ups to assess the impact on their condition.

How Is the Trial Designed?

Group I: Part C Pazopanib - 150 mg Experimental Treatment 1 Intervention

Pazopanib 150 mg oral daily dosing (six 25 mg Pazopanib capsules).

Group II: Part B (Severe Anemia) Pazopanib - 150 mg Active Control 1 Intervention

150 mg pazopanib oral capsules (six 25 mg placebo capsules daily).

Group III: Part B (Severe Epistaxis) Pazopanib - 150 mg Active Control 1 Intervention

Pazopanib 150 mg oral daily dosing (six 25 mg Pazopanib capsules).

Group IV: Part B (Severe Anemia) Placebo Placebo Group 1 Intervention

Placebo oral capsules (six 25 mg placebo capsules daily).

Group V: Part B (Severe Epistaxis) Placebo Placebo Group 1 Intervention

Placebo oral capsules (six 25 mg placebo capsules daily).

Pazopanib is already approved in United States, European Union, China for the following indications:

Approved in United States as Votrient for:

• Advanced renal cell carcinoma (kidney cancer)
• Soft tissue sarcoma

Approved in European Union as Votrient for:

• Advanced renal cell carcinoma (kidney cancer)
• Soft tissue sarcoma

Approved in China as pazopanib for:

• Metastatic renal cell carcinoma (mRCC)

Who Is Running the Clinical Trial?

Cure HHT

Lead Sponsor

Trials

4

Recruited

10,400+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

In a proof-of-concept study involving seven patients with hereditary hemorrhagic telangiectasia (HHT), pazopanib at a low dose of 50 mg daily led to significant reductions in epistaxis duration and improvements in hemoglobin levels, indicating its potential efficacy for treating HHT-related bleeding.

The study reported no serious adverse events, with only one severe adverse event leading to withdrawal, suggesting that pazopanib can be safely administered at lower doses than typically used for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia. Faughnan, ME., Gossage, JR., Chakinala, MM., et al.[2022]

Pazopanib, a multikinase inhibitor, was approved by the US FDA in October 2009 for treating advanced renal cell carcinoma, highlighting its significance in cancer therapy.

The drug targets vascular endothelial growth factor receptors, which play a crucial role in tumor growth and blood vessel formation, making it an effective option for managing this type of kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib. Bukowski, RM., Yasothan, U., Kirkpatrick, P.[2021]

A patient with hereditary hemorrhagic telangiectasia (HHT) experienced severe nosebleeds that did not respond to multiple treatments, including six cycles of bevacizumab, but showed dramatic improvement after starting pazopanib, a drug that targets VEGF receptor-2 signaling.

After beginning pazopanib at a dose of 100 mg, the patient not only saw significant reductions in epistaxis but also normalized hemoglobin and iron levels, eliminating the need for iron infusions and blood transfusions for 12 months, suggesting pazopanib's potential efficacy in treating HHT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib effective for bevacizumab-unresponsive epistaxis in hereditary hemorrhagic telangiectasia. Parambil, JG., Woodard, TD., Koc, ON.[2021]

Pazopanib significantly improves progression-free survival in patients with chemotherapy-failing nonadipocytic soft tissue sarcomas, increasing it from 1.6 months to 4.6 months based on Phase II and Phase III clinical trials.

The safety profile of pazopanib is manageable, allowing for high dose intensity over time, making it a viable option as part of the standard care for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib, a new therapy for metastatic soft tissue sarcoma. Verweij, J., Sleijfer, S.[2021]

In a study using a mouse model of hereditary hemorrhagic telangiectasia (HHT), the antiangiogenic drugs sorafenib and a pazopanib analog significantly improved anemia and reduced gastrointestinal bleeding, while erlotinib worsened anemia.

The findings suggest that oral antiangiogenic tyrosine-kinase inhibitors are more effective for treating gastrointestinal bleeding in HHT patients than for preventing the development of skin arteriovenous malformations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective effects of oral antiangiogenic tyrosine kinase inhibitors on an animal model of hereditary hemorrhagic telangiectasia. Kim, YH., Kim, MJ., Choe, SW., et al.[2023]

In a study of 13 patients with hereditary hemorrhagic telangiectasia (HHT) treated with pazopanib for a median of 22 months, all patients achieved transfusion independence, indicating the drug's effectiveness in managing severe bleeding associated with HHT.

Pazopanib significantly improved hemoglobin levels and reduced epistaxis severity, with a 93% reduction in RBC transfusions and a 92% decrease in iron infusions during the first 3 months of treatment, while being well-tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia. Parambil, JG., Gossage, JR., McCrae, KR., et al.[2022]

Antiangiogenic therapies, such as intravenous bevacizumab, oral pazopanib, and oral thalidomide, have shown to be effective and safe in managing bleeding associated with hereditary hemorrhagic telangiectasia (HHT), providing durable hemostasis and improving patients' quality of life.

Despite the promising results, there is a lack of comprehensive guidelines for the clinical use of these therapies in HHT, highlighting the need for further research and expert guidance to optimize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Antiangiogenic Therapies for Bleeding in Hereditary Hemorrhagic Telangiectasia: A Practical, Evidence-Based Guide for Clinicians. Al-Samkari, H.[2022]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6510884/

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PAZOPANIB CLINICAL TRIAL

Researchers want to determine if the investigational drug, Pazopanib, will lessen nosebleed severity in patients with Hereditary Hemorrhagic Telangiectasia (HHT) ...

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mayo.edu

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Effects of Pazopanib on Hereditary Hemorrhagic ...

Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT. We analyzed outcomes of HHT patients with ...

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pubmed.ncbi.nlm.nih.gov

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Pazopanib in treatment of hereditary hemorrhagic ...

Pazopanib may be a reasonable option for patients with HHT with epistaxis or gastrointestinal bleeding that are refractory to standard treatment.

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uclahealth.org

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Effects of Pazopanib on Hereditary Hemorrhagic ...

The investigators will study whether Pazopanib, taken daily for 24 weeks, will reduce the severity of nose bleeds in patients with hereditary hemorrhagic ...