Bevacizumab in Adults With Recurrent Respiratory Papillomatosis (RRP)

NCT05797246 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001572001572-C
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Human Papilloma Virus; Dose Escalation; laryngotracheal disease; papillomatous disease

Outcome Measures

Primary Outcomes (1)

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

  Determined by measuring the mean duration between successive clinically indicated surgeries in the 12 months during treatment for that participant and determining whether that duration is longer than the mean duration between successive clinically indicated surgeries in the 12 months prior to treatment by one month or more. This fraction of participants who are classified as having a success will be reported along with a 95% confidence interval.

  1 year

Secondary Outcomes (4)

• Rate of pulmonary RRP partial response (PR) and complete response (CR) by RECIST 1.1 in participants with pulmonary disease.

  6 weeks after completion of treatment

• Recurrence free interval after treatment

  Weeks 6, 12, 24 and remote assessment (if needed)

• The safety of systemic bevacizumab in participants with aggressive RRP

  42 days after the study agent was last administered

• The rate of papilloma regrowth by determining the percentage of participants with an increase in their surgery-free interval after treatment with systemic bevacizumab

  Weeks 6, 12, 24 after completion of treatment, every 3 months after that with the last evaluation performed at 1 year after completion of study treatment

Study Arms (1)

Arm 1

EXPERIMENTAL

Bevacizumab treatment course

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

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.

Arm 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

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

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Scott M Norberg, D.O.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2023
• First Posted: April 4, 2023
• Study Start: August 2, 2023
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: May 29, 2026

Record last verified: 2026-01-22

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)