Combination Bevacizumab and PRGN-2012 in Adults With Recurrent Respiratory Papillomatosis (RRP)
A Phase II Study of Combination Bevacizumab and PRGN-2012 in Adults With Recurrent Respiratory Papillomatosis (RRP)
2 other identifiers
interventional
50
1 country
1
Brief Summary
Background: Recurrent respiratory papillomatosis (RRP) is a rare disease that causes wart-like growths called papillomas to grow in the airway, most often in the voice box, windpipe, or lungs. These growths can make it hard to speak or breathe. Surgery can remove the papillomas, but they often come back. In some cases, they can become cancerous. Objective: This study istesting whether two treatments used together (PRGN-2012, a vaccine-based treatment and bevacizumab, a drug that affects blood vessel growth) can help control RRP and reduce the chance that papillomas will grow back. Eligibility: Adults aged 18 years and older may be able to join the study if they have RRP and meet certain treatment history requirements. This may include people who have previously received PRGN-2012 or bevacizumab, or people who have needed more than 2 surgeries to remove papillomas. Design: Before starting treatment, participants will have screening tests to make sure the study is safe for them. These tests may include a physical exam with blood and urine tests, heart function testing, imaging scans, and an endoscopy. During an endoscopy, a thin, flexible tube with a small camera will look at the inside of the nose, throat, voice box, and upper windpipe. Participants will receive study treatment during 7 clinic visits over about 6 months. Bevacizumab is given through a vein amd PRGEN-2012 is given as an injection under the skin of the arm or leg. Participants may receive 1 or both drugs at each visit. After completing treatmen, participants will return for 4 follow-up visits over 1 year. These visits may include repeat imaging, blood and urine tests, and other exams. After that, the study team will contact participantsby phone or email every 3 months for 2 years. If their RRP gets worse during the follow-up period, they may be able to receive a second course of treatment using the same schedule....
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Aug 2026
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 8, 2026
CompletedFirst Posted
Study publicly available on registry
August 11, 2026
CompletedStudy Start
First participant enrolled
August 16, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2029
Study Completion
Last participant's last visit for all outcomes
July 1, 2030
August 11, 2026
August 5, 2026
2.9 years
August 8, 2026
August 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To determine the complete response rate, defined as the percentage of participants who do not require an intervention (either medical or surgical) in the 12 months following completion of treatment with combination systemic bevacizumab and PRGN-...
Determined by measuring the number of participants (evaluable for clinical response) who do not require an intervention (either medical or surgical) in the 12 months following completion of treatment. This fraction of participants who are classified as having a complete response at 12 months will be reported along with 80% and 95% two-sided confidence intervals. For participants receiving re-treatment, any increase in their treatment-free interval following re-treatment will not be used for evaluation of the primary endpoint.
From baseline to 12 months after treatment
Secondary Outcomes (5)
To determine the recurrence-free interval of laryngotracheal papillomatous disease after combination treatment
Baseline through 3 years after treatment
To determine the safety of the combination of bevacizumab and PRGN-2012
Between the first dose of drug on D1 through 6 weeks, as well as on the 6-week safety follow-up visit. After 6-week safety follow-up visit, only adverse events that are serious and related to the study interventions
To determine the treatment-free interval (either medical or surgical) after completion of treatment with combination systemic bevacizumab and PRGN-2012
Up to 3 years after treatment
To determine the overall response rate (ORR) of pulmonary RRP defined as complete response (CR) and partial response (PR) by RECIST 1.1 in participants with measurable pulmonary disease after combination treatment
Baseline and 6 weeks after completion of treatment
To determine the treatment-free interval (either medical or surgical) after completion of retreatment with combination systemic bevacizumab and PRGN-2012
Baseline through 3 years after treatment
Study Arms (1)
Arm 1
EXPERIMENTALParticipants with RRP will be given Bevacizumab and PRGN-2012
Interventions
Administration of IV bevacizumab will be done on D1, D22, D43, D85, and D170 at a dose of 10 mg/kg during Course 1 (and Course 2 if applicable).
Eligibility Criteria
You may qualify if:
- Histological or cytological diagnosis of RRP confirmed by pathology report. Note: If there is no documentation or archival sample, a biopsy will be done to confirm the diagnosis.
- Age \>= 18 years old.
- A history of 2 or more surgeries or use of IV bevacizumab in order to control laryngeal and/or tracheal RRP within 12 months prior to the study treatment initiation.
- Previous treatment with PRGN-2012 (zopapogene imadenovec \[Papzimeos\]).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Participants must have an adequate organ and marrow function as defined below:
- White blood cells (WBC) \>2,000/mcL
- Absolute neutrophil count (ANC) \>= 1,000/mcL
- Hemoglobin \> 9.0 g/dL
- Platelets \>= 100,000/mcL
- Total bilirubin \<= 1.5 mg/dL. Note: participants with Gilbert s Syndrome must have a total bilirubin \< 3.0 mg/dL
- Aspartate aminotransferase (AST) \<= 2.5 X institutional upper limit of normal (ULN)
- Alanine aminotransferase (ALT) \<=2.5 X institutional 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.
- +5 more criteria
You may not qualify if:
- History of significant cardiovascular disease or thromboembolic event: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (\>= New York Heart Association Classification Class II) occurring within 12 months prior to the study treatment initiation
- Serious cardiac arrhythmia requiring medication as assessed by electrocardiogram (EKG) at screening.
- Any investigational agents within 4 weeks prior to the study treatment initiation.
- Systemic medical RRP therapy within 4 weeks or 3 half-lives, whichever is longer prior to the study treatment initiation.
- Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to the study treatment initiation. Note: Inhaled, topical intranasal or intraocular steroids, and adrenal replacement doses \<10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- History of abdominal fistula or gastrointestinal perforation within 12 months prior to the study treatment initiation.
- Major surgery within 4 weeks prior to the study treatment initiation. Note: The surgery is considered major if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges).
- Non-healing wounds, active ulcer, or untreated bone fracture.
- History of hemoptysis (\>2.5 mL of bright red blood per episode) within 1 month prior to the study treatment initiation.
- History of serious hemorrhage (CTCAE Grade 4) within 12 months prior to the study 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 the study treatment initiation.
- Inadequately controlled hypertension (defined as systolic blood pressure (BP) \>150 mmHg and/or diastolic blood pressure \> 100 mmHg). Note: an average of 3 BP readings on 2 sessions will be used to measure blood pressure if the initial reading indicates inadequately controlled hypertension. 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 CTCAE. Note: Alopecia, sensory neuropathy Grade \<= 2 are acceptable.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Scott M Norberg, D.O.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 8, 2026
First Posted
August 11, 2026
Study Start (Estimated)
August 16, 2026
Primary Completion (Estimated)
July 1, 2029
Study Completion (Estimated)
July 1, 2030
Last Updated
August 11, 2026
Record last verified: 2026-08-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
- Access Criteria
- Clinical data will be made available upon request and with the permission of the study PI.
This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review.