Bevacizumab for Respiratory Warts

Overseen By Melissa L Wheatley

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug bevacizumab (also known as Avastin) can assist individuals with recurrent respiratory papillomatosis (RRP), a condition characterized by wart-like growths in the airways, in reducing the need for frequent surgeries. The goal is to determine if bevacizumab can decrease the number of surgeries required to manage these growths. Individuals who have undergone two or more surgeries in the past year to remove these growths may be suitable candidates for this trial. Participants will receive bevacizumab intravenously and attend regular clinic visits for about a year. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that bevacizumab is likely to be safe for humans?

Research has shown that bevacizumab is generally safe for people with recurrent respiratory papillomatosis (RRP). Studies have found that even higher doses are relatively safe for adults with this condition. Reports also suggest that systemic use of bevacizumab is well tolerated and helps reduce symptoms.

In some cases, applying bevacizumab directly to the growths in the airways led to significant improvement. Most patients experienced either complete remission (no more growths) or only a small return of the growths. Additionally, reports of safe treatment in children with RRP support its safety in adults.

Overall, evidence suggests that bevacizumab is a safe treatment option for people with RRP. However, as with any treatment, monitoring for side effects is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Bevacizumab is unique because it targets the blood vessels that supply respiratory warts, potentially reducing their size and number. Unlike standard treatments like surgical removal or laser therapy, which physically remove the warts, bevacizumab works by inhibiting angiogenesis, the process of new blood vessel formation. This approach could lead to less invasive and more effective management of respiratory warts, minimizing the need for repeated procedures. Researchers are excited about this treatment because it offers a novel way to tackle the root cause of the growths rather than just the symptoms.

What evidence suggests that bevacizumab might be an effective treatment for respiratory warts?

Research shows that bevacizumab, which participants in this trial will receive, holds promise for people with recurrent respiratory papillomatosis (RRP). Studies have found that in 95% of cases, bevacizumab reduces the need for repeated surgeries to remove airway growths. One study reported a 100% response rate after the third treatment. Bevacizumab blocks a protein that aids blood vessel growth, helping prevent the growths from returning. This method has proven effective even in the most severe cases of RRP. ^{2 3 6 7 8}

Who Is on the Research Team?

Scott M Norberg, D.O.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 need surgery to remove my papilloma as per my doctor's advice.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9363326/

Bevacizumab as treatment option for recurrent respiratory ... Efficacy of systemic bevacizumab. The outcomes of the studies describing efficacy of systemic bevacizumab are presented in Table 3. In 95% of the cases (41 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05797246

NCT05797246 | Bevacizumab in Adults With Recurrent ... 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.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2468548823000395

The effect of bevacizumab (Avastin) in treating Juvenile ... This report is a case analysis on the effect of bevacizumab (Avastin) in treating JoRRP. The new clinical remedy is based on case details and reported findings.

4. pure.johnshopkins.edu pure.johnshopkins.edu/en/publications/efficacy-of-systemic-bevacizumab-for-recurrent-respiratory-papill

Efficacy of Systemic Bevacizumab for Recurrent ... Conclusion: Systemic bevacizumab is effective in stabilizing progression in even the most severe cases of RRP, with both a dramatic reduction in laryngeal and ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/lary.31706

Quantifying Bevacizumab Efficacy in Recurrent Respiratory ... The overall response rate increased from 75% after the first treatment to 100% after the third. Among patients with localized lesions who ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23012897/

Safety and dosing of bevacizumab (avastin) for the ... Conclusions: This investigation provides evidence that higher doses of bevacizumab are relatively safe in adult patients with laryngeal RRP. Further refinements ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165587624002921

Evaluating the efficacy and safety of intralesional ... Where reported, complete remission or minimal recurrence was identified in 34/38 (89 %) patients following treatment with intralesional bevacizumab. However, ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)59345-0/fulltext

Systemic bevacizumab for the treatment of recurrent ... Systemic bevacizumab appears to be a safe and well tolerated treatment option for patients with severe RRP. It demonstrates promising efficacy on symptoms.