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....
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]).
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.
Single group
PRGN-2012
DrugPRGN-2012 (5x10\^11 PU) will be administered on Days 85, 100, 128, and 170.
Bevacizumab
DrugAdministration 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).
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.
To determine the recurrence-free interval of laryngotracheal papillomatous disease after combination treatment
The time to recurrence of papillomatous disease after completion of treatment will be recorded and reported descriptively.
To determine the safety of the combination of bevacizumab and PRGN-2012
AEs will be reported by type and grade.
To determine the treatment-free interval (either medical or surgical) after completion of treatment with combination systemic bevacizumab and PRGN-2012
Reported descriptively by measuring the duration between completion of combination treatment and the time to the requirement of the first clinical intervention (either medical or surgical) following completion of protocol therapy.
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
The fraction of participants with a pulmonary RRP partial response and a pulmonary RRP complete response will be reported in all treated pulmonary participants, along with 95% confidence intervals for each.
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