A Phase II Study of Bevacizumab in Adults With Recurrent Respiratory Papillomatosis (RRP)
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.
• Age \>= 18 years old.
• Histologically confirmed diagnosis of RRP.
• Individuals must require procedure(s) to remove papillomatous disease per standard of care.(not required for re-treatment)
• 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 (not required for re-treatment):
‣ 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)
⁃ Tracheostomy.
• ECOG performance status of 0-1.
• Individuals 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
∙ OR
∙ Creatinine Clearance (CrCl): \>=60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal (calculated using the Cockcroft-Gault formula).
• 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
‣ Individuals 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 individual is also acceptable.
⁃ Breastfeeding individuals must be willing to discontinue breastfeeding from study treatment initiation through 6 months after bevacizumab treatment discontinuation.
⁃ All individuals must have the ability to understand and willingness to sign a written informed consent.
⁃ All individuals must be willing to undergo mandatory biopsy during the study (not applicable for re-treatment).