Bevacizumab in Adults With Recurrent Respiratory Papillomatosis (RRP)

Neoplasms Clinical Trial

Official title: A Phase II Study of Bevacizumab in Adults With Recurrent Respiratory Papillomatosis (RRP)

Status Recruiting

Clinical Trial Summary

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.

Clinical Trial Description

Background:

• Recurrent respiratory papillomatosis (RRP) is a rare papillomatous disease of the respiratory tract that is caused by Human Papilloma Virus (HPV) types 6 or 11.

• RRP can progress to cause severe voice disturbance, airway compromise, fatal pulmonary lesions, and rarely invasive cancers.

• There is no approved systemic therapy for RRP. Participants require repeated surgical procedures for disease debridement and control.

• Translational research studies have shown high levels of vascularity in papilloma tissue driven in part by high levels of vascular endothelial growth factor (VEGF)-A mRNA, vascular endothelial growth factor receptors (VEGFR)-1 and VEGFR-2 and elevated serum levels of VEGF-A, particularly in cases of aggressive RRP.

• Papillomas are also infiltrated by immunosuppressive myeloid and regulatory T-cells.

• Systemic inhibition of VEGF signaling may reduce VEGF-driven angiogenesis in papillomas and reduce chemotaxis and expansion of immunosuppressive myeloid cells and regulatory T-cells.

• Bevacizumab is a recombinant humanized monoclonal antibody that binds all active forms of VEGF-A.

• Bevacizumab is FDA approved for the treatment of metastatic colorectal cancer, non-small cell lung cancer, metastatic renal cell carcinoma, recurrent glioblastoma, cervical cancer, epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer and was selected for its demonstrated activity in a variety of cancers and for its acceptable safety profile.

• Use of systemic bevacizumab in patients with severe and/or tracheal RRP has not been studied prospectively in controlled clinical studies, but clinical safety and activity has been reported in retrospective single institution case series.

Objective:

-To determine the percentage of participants with an increase in their surgery-free interval during treatment with systemic bevacizumab

Eligibility:

• Histologically confirmed diagnosis of RRP

• A history of 2 or more surgeries in the last 12 months in order to control laryngeal and/or tracheal RRP

• At least one of the following:

• A Derkay score of 8 or greater

• Pulmonary RRP with disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

• Tracheostomy

• Age >=18 years old

• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1

Design:

• This is a phase II, single arm clinical trial evaluating systemic bevacizumab.

• Participants will receive bevacizumab (10 mg/kg IV) every three weeks for 3 cycles and then every 6 weeks for a total treatment course of 11 cycles for approximately 1 year total.

• Operative examination under anesthesia (EUA) with biopsies for research and possible papilloma debulking for safety will be performed before dose 1 and following dose 2, optional EUA for research biopsies will be performed at cycles 6 and 11.

• Participants may undergo standard-of-care operative EUA with papilloma cleanout during the 1-year treatment period as clinically indicated at the NIH.

• The mean surgery-free interval during the 1-year treatment period will be compared to the mean surgery-free interval in the 12 months prior to treatment.

• Participants will also be assessed for papilloma recurrence and surgery-free interval at 6, 12, 24 weeks and every 3 months after that until 1 year following completion of treatment.

• A total of 20 evaluable participants will be treated on study. ;

Related Conditions & MeSH terms

• Communicable Diseases
• Disease Attributes
• DNA Virus Infections
• Infections
• Neoplasms
• Neoplasms by Histologic Type
• Neoplasms, Glandular and Epithelial
• Neoplasms, Squamous Cell
• Papilloma
• Papillomavirus Infections
• Pathologic Processes
• Recurrence
• Respiratory Tract Diseases
• Respiratory Tract Infections
• Tumor Virus Infections
• Virus Diseases

• NCT number: NCT05797246
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Melissa Missy L Wheatley
• Phone: (240) 858-3391
• Email: melissa.wheatley@nih.gov
• Status: Recruiting
• Phase: Phase 2
• Start date: August 2, 2023
• Completion date: November 2, 2026