Bevacizumab in Adults With Recurrent Respiratory Papillomatosis (RRP)

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. * Bevacizumab resistance can develop in cancer patients due to a variety of tumor escape mechanisms that are unlikely to occur in RRP patients with normal endothelial cells, but bevacizumab re-treatment for recurrent RRP has not been evaluated in controlled clinical studies. 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 * Tracheal involvement with RRP that has required two or more clinical interventions in the last 12 months * 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, optional EUA for research biopsies may be performed following dose 2 and 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. * During the follow up period, up to 15 participants who develop sufficient papilloma recurrence to require a clinical intervention may be re-treated with 11 additional cycles of bevacizumab (10 mg/kg IV) following the same schedule as the initial treatment. * Prior to the initiation of re-treatment, an optional operative EUA with biopsies for research and possible papilloma debulking for safety may be performed.