Bevacizumab in Adults With Recurrent Respiratory Papillomatosis (RRP)

Eligibility Criteria

• * Age \>= 18 years old.
• * Histologically confirmed diagnosis of RRP.
• * Participants must require procedure(s) to remove papillomatous disease per standard of care.
• * A history of 2 or more surgeries within 12 months prior to treatment initiation in order to control laryngeal and/or tracheal RRP (not required for re-treatment).
• * At least one of the following:
• * A Derkay score of 8 or greater
• * Measurable disease per RECIST 1.1 (participants with pulmonary RRP only)
• * Tracheal involvement with RRP that has required two or more clinical interventions in the last 12 months (two or more clinical interventions not required for re-treatment)
• * Tracheostomy.
• * ECOG performance status of 0-1.
• * Participants must have adequate organ and marrow function as defined below:
• * White blood cells (WBC): \>2,000/microL
• * Absolute neutrophil count (ANC): \>=1,500/microL
• * Hemoglobin: \>9.0 g/dL
• * Platelets: \>=100,000/microL
• * Total bilirubin: \<=1.5 mg/dL, except in participants with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dL
• * Aspartate aminotransferase (AST) /Alanine aminotransferase (ALT): \<=2.5 X institutional upper limit of normal (ULN)
• * Creatinine: within normal institutional limits
• * Prothrombin time (PT) /International normalized ratio (INR) and Partial thromboplastin time (PTT): \<=1 X institutional ULN. In participants on anticoagulation, coagulation tests should be within a therapeutic range.
• * Urinalysis: Urine dipstick \< 2+ proteinuria. In participants with \>=2+ proteinuria on dipstick urinalysis should undergo a 24-hour urine collection and must demonstrate \<=1g of protein in 24 hours to be eligible
• * Participants must have received their last systemic therapy for RRP \> 4 weeks or 5 half-lives, whichever is longer, prior to treatment initiation, except for systemic bevacizumab which must be \> 1 year prior to treatment initiation (not applicable for re-treatment)
• * Individuals able to become pregnant and their partners must agree to use highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization ) for the duration of bevacizumab treatment and up to 6 months after completion of bevacizumab treatment. Note: abstinence, defined as no heterosexual sexual intercourse when this is in line with the preferred and usual lifestyle of the participant is also acceptable.
• * Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 6 months after bevacizumab treatment discontinuation.
• * All participants must have the ability to understand and willingness to sign a written informed consent.
• * All participants must be willing to undergo mandatory biopsy during the study.
• * History of abdominal fistula or gastrointestinal perforation within 6 months prior to treatment initiation.
• * Major surgery within 4 weeks prior to treatment initiation.
• * Non-healing wound, active ulcer, or untreated bone fracture.
• * History of hemoptysis (\>2.5 mL of bright red blood per episode) within 1 month prior to treatment initiation.
• * Evidence of bleeding diathesis or significant coagulopathy (with or without current therapeutic anticoagulation).
• * Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to treatment initiation.
• * Inadequately controlled hypertension (defined as systolic blood pressure (BP) \>150 mmHg and/or diastolic blood pressure \> 100 mmHg), an average of 3 BP readings on 2 sessions will be used to measure blood pressure if initial reading indicates inadequately controlled hypertension. NOTE: anti-hypertensive therapy to achieve blood pressures below these parameters is allowed.
• * Prior history of hypertensive crisis or hypertensive encephalopathy.
• * Persisting toxicity related to prior therapy of Grade \>1 per Common Terminology Criteria for Adverse Events (CTCAE) v 5.0. NOTE: alopecia, sensory neuropathy Grade \<=2 are acceptable.
• * Known active alcohol or drug abuse.
• * History of allergy to study drug components.
• * Pregnancy (confirmed with Beta-Human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test in WOCBP performed at screening).
• * Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.