Bevacizumab for Respiratory Warts

Overseen By Scott M Norberg, D.O.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Cardiovascular disease, Hypertension, Drug abuse, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

Duration: 1 year

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Recurrent respiratory papillomatosis (RRP) is a rare disease that causes wart-like growths in the airways. These growths come back when removed; some people may need 2 or more surgeries per year to keep their airways clear. Better treatments are needed. Objective: To see if a drug called bevacizumab can reduce the number of surgeries needed in people with RRP. Eligibility: People aged 18 and older with recurrent RRP; they must need surgery to remove the growths in their airways. Design: Participants will be screened. Their ability to breathe and speak will be evaluated. They will have an endoscopy: a flexible tube with a light and camera will be inserted into their nose and throat. They will have a test of their heart function and imaging scans of their chest. Participants will have surgery to remove the growths in their airways. Bevacizumab is given through a small tube placed in a vein in the arm. After the surgery, participants will receive 11 doses of this drug: every 3 weeks for 3 doses, and then every 6 weeks for 8 more doses. They will come to the clinic for each dose; each visit will be about 8 hours. Tissue samples of the growths will be collected after the second treatment; this will be done under general anesthesia. Participants may undergo apheresis: Blood will be drawn from a needle in an arm. The blood will pass through a machine that separates out the cells needed for the study. The remaining blood will be returned to the body through a second needle. Follow-up will continue for 1 year after the last treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have stopped any systemic therapy for RRP more than 4 weeks or 5 half-lives before starting the trial, except for bevacizumab, which must be stopped more than 1 year prior.

Is bevacizumab safe for treating respiratory warts?

Bevacizumab, also known as Avastin, has been used safely in various conditions, but it can cause side effects like high blood pressure, protein in urine, and bleeding. These side effects are usually mild to moderate and manageable, but more severe issues like bleeding in the lungs have been reported in some cases. ^{1 2 3 4 5}

How is the drug Bevacizumab unique in treating respiratory warts?

Bevacizumab is unique because it targets and inhibits vascular endothelial growth factor (VEGF), which is involved in the growth of blood vessels that support the warts. Unlike other treatments, it can be administered systemically (throughout the body) or directly into the lesions, offering a novel approach for severe cases that do not respond to other therapies. ^{1 2 6 7 8}

Research Team

Scott M Norberg, D.O.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with recurrent respiratory papillomatosis (RRP) needing frequent surgeries for airway growth removal. Must have had at least two surgeries in the past year, be willing to sign consent and undergo biopsies, have good organ function and performance status, not received certain treatments recently, and agree to contraception if applicable.

Inclusion Criteria

I've had 2 or more surgeries in the last year for laryngeal or tracheal RRP.

I am 18 years old or older.

I have a Derkay score of 8 or more, measurable disease, a tracheostomy, or I am mostly self-sufficient.

Exclusion Criteria

I have not coughed up more than a teaspoon of bright red blood in the last month.

I haven't had a serious heart issue or stroke in the last 6 months.

I have not had a gut perforation or abnormal connection in my belly in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Surgery

Participants will have surgery to remove the growths in their airways

1 day

1 visit (in-person)

Treatment

Participants receive bevacizumab every 3 weeks for 3 doses, then every 6 weeks for 8 more doses

1 year

11 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Regular assessments every 3 months

Treatment Details

Interventions

• Bevacizumab

Trial Overview The trial is testing Bevacizumab's effectiveness in reducing surgery frequency for RRP patients. Participants will receive the drug intravenously post-surgery every three weeks initially then every six weeks, accompanied by evaluations including endoscopy and heart function tests.

Participant Groups

Group I: Arm 1 Experimental Treatment 1 Intervention

Bevacizumab treatment course

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

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

A study involving 43 adult patients receiving higher doses of bevacizumab (15 to 88 mg) for recurrent respiratory papillomatosis (RRP) showed no local or systemic complications, indicating that higher doses are relatively safe.

The treatment was effective, as 63 out of 100 injection sessions included KTP laser photoangiolysis before bevacizumab, and no dysfunction was observed in patients, suggesting that this combination may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and dosing of bevacizumab (avastin) for the treatment of recurrent respiratory papillomatosis. Best, SR., Friedman, AD., Landau-Zemer, T., et al.[2017]

Bevacizumab, a VEGF inhibitor, showed significant and sustained improvement in controlling severe juvenile-onset recurrent respiratory papillomatosis (RRP) over a 5-year period, despite the patient being refractory to other treatments.

However, after 3 years of treatment, the patient developed hypertension and proteinuria, along with evidence of glomerular thrombotic microangiopathy, highlighting the need for careful monitoring of renal complications in children receiving VEGF inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal Implications of Long-Term Systemic Bevacizumab for Recurrent Respiratory Papillomatosis. Robinson, CH., Hart-Matyas, M., Morgenstern, DA., et al.[2023]

Bevacizumab (Avastin) effectively targets VEGF to inhibit tumor angiogenesis, showing a safety profile that includes mostly mild to moderate side effects such as hypertension and proteinuria, which are manageable in clinical settings.

The side effects associated with bevacizumab, including rare but serious events like gastrointestinal perforation and arterial thrombosis, do not typically exacerbate the toxicity of standard chemotherapy, making it a suitable adjunct treatment for metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. Gordon, MS., Cunningham, D.[2015]

Bevacizumab, when combined with chemotherapy, significantly improves clinical outcomes and delays disease progression in patients with advanced non-squamous non-small-cell lung cancer (NSCLC), as demonstrated in pivotal phase III trials involving large patient populations.

The safety profile of bevacizumab is well-characterized, with manageable adverse events such as hypertension and bleeding, and the overall incidence of serious side effects is similar to that of placebo, indicating it can be safely administered in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging safety data for bevacizumab in advanced non-small-cell lung cancer. Hirsh, V.[2015]

Bevacizumab (Avastin®) is the only antiangiogenic agent approved for first-line treatment of advanced non-small-cell lung cancer (NSCLC) in eligible patients, effectively targeting the VEGF signaling pathway to inhibit tumor growth and metastasis.

While there are concerns about severe side effects like pulmonary hemorrhage, recent studies suggest that bevacizumab is safe and well-tolerated even in patients typically excluded from clinical trials, indicating potential for broader use in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in the treatment of NSCLC: patient selection and perspectives. Russo, AE., Priolo, D., Antonelli, G., et al.[2023]

In a study involving 3 children aged 3 to 6 years with severe recurrent respiratory papilloma (RRP), treatment with intralesional bevacizumab after surgical interventions led to increased time between necessary operations, suggesting a potential benefit in managing this condition.

Two of the children showed significant improvements in their RRP severity and quality of life scores, indicating that bevacizumab may help reduce the frequency of treatments, although further research is needed to confirm these findings and assess the overall efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of 532-nm pulsed potassium titanyl phosphate laser and adjuvant intralesional bevacizumab for aggressive respiratory papillomatosis in children: initial experience. Maturo, S., Hartnick, CJ.[2015]

A 12-year-old girl with severe recurrent laryngeal papillomatosis showed remarkable improvement after receiving intravenous bevacizumab, with complete resolution of her laryngeal disease and significant reduction in tracheal involvement within 3 months.

The use of systemic bevacizumab appears to be a safe and effective adjuvant therapy for severe papillomatosis, as the patient experienced no major or minor complications during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab chemotherapy for management of pulmonary and laryngotracheal papillomatosis in a child. Zur, KB., Fox, E.[2018]

Bevacizumab, a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), has shown promising efficacy in treating extensive cases of recurrent respiratory papillomatosis (RRP), which is caused by human papillomavirus (HPV).

This case report highlights the successful management of two patients with extensive airway and lung involvement of RRP using systemic bevacizumab, suggesting its potential as a treatment option beyond localized disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Center Experience of Two Cases. Bedoya, A., Glisinski, K., Clarke, J., et al.[2019]

References

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

Safety and dosing of bevacizumab (avastin) for the treatment of recurrent respiratory papillomatosis. [2017]

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

Renal Implications of Long-Term Systemic Bevacizumab for Recurrent Respiratory Papillomatosis. [2023]

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

Managing patients treated with bevacizumab combination therapy. [2015]

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

Emerging safety data for bevacizumab in advanced non-small-cell lung cancer. [2015]

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

Bevacizumab in the treatment of NSCLC: patient selection and perspectives. [2023]

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

Use of 532-nm pulsed potassium titanyl phosphate laser and adjuvant intralesional bevacizumab for aggressive respiratory papillomatosis in children: initial experience. [2015]

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

Bevacizumab chemotherapy for management of pulmonary and laryngotracheal papillomatosis in a child. [2018]

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

Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Center Experience of Two Cases. [2019]