Bevacizumab in Adults With Recurrent Respiratory Papillomatosis (RRP)

• Status: Not yet recruiting
• Trial end date: 2026-11-02
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Bevacizumab

Criteria

• INCLUSION 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.

• At least one of the following:

• A Derkay score of 8 or greater

• Measurable disease per RECIST 1.1 (participants with pulmonary RRP only)

• 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

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

• Urinalysis: No proteinuria. Urine dipstick < 2. 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

• Women of child-bearing potential (WOCBP) and men 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.

EXCLUSION CRITERIA:

-History of significant (i.e., active) cardiovascular disease or thromboembolic event:

cerebral vascular accident/stroke (within 6 months prior to treatment initiation), myocardial infarction (within 6 months prior to treatment initiation), unstable angina, congestive heart failure (>= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication as assessed by EKG.

• 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.