Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis
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|ClinicalTrials.gov Identifier: NCT04724980|
Recruitment Status : Recruiting
First Posted : January 26, 2021
Last Update Posted : May 11, 2021
Recurrent respiratory papillomatosis (RRP) is a rare disease. It is caused by the human papillomavirus (HPV). RRP affects the upper and lower respiratory tracts. It is difficult to treat and can be fatal. Researchers want to see if PRGN-2012 can help.
To find a safe, tolerable dose of PRGN-2012 and to see if it works in treating RRP.
Adults 18 and older who have RRP
Participants will be screened with a medical history and physical exam. They will have blood tests and viral studies. They may have a computed tomography (CT) scan of the neck and/or chest. The structures inside their nose, throat, larynx (voice box), and upper windpipe will be viewed using a small tube with a built-in camera (endoscope). Their arm veins will be evaluated. They will have a pregnancy test, if needed.
Screening tests will be repeated during the study.
Participants will have surgery. Their papilloma will be removed. They will have another surgery if it grows back. They will have to stay at the hospital for 1 to 2 days after each surgery.
Participants will complete questionnaires about how much RRP affects their voice.
Participants will get PRGN-2012 as an injection under the skin on days 1, 15, 43, and 85.
Participants may have optional leukapheresis.
Participants will have visits 6, 12, and 24 weeks after their last dose of PRGN-2012. These visits will assess the safety of PRGN-2012 and disease response to the treatment. After the 24-week visit, participants will be called every 3 months for 2 years.
Participation will last for up to 3 years.
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Respiratory Papillomatosis Papillomavirus Infections Papillomaviridae||Drug: PRGN-2012||Phase 1|
Recurrent respiratory papillomatosis (RRP) is a rare papillomatous disease of the aerodigestive tract that is caused by Human Papilloma Virus (HPV) types 6 or 11.
RRP can progress to cause severe voice disturbance, airway compromise, fatal pulmonary lesions, and invasive cancers.
There is no proven effective systemic therapy for RRP that leads to cure. Participants require repeated surgical procedures for disease debridement and control.
A recently completed phase II clinical trial investigating avelumab in subjects with RRP demonstrated an acceptable safety profile from avelumab and a high rate of partial responses, but no participants were cured.
Laboratory analysis revealed that the ability to measure infiltration of papillomas by HPV antigen-specific T-cells is rare.
A therapeutic vaccine may induce de novo HPV antigen-specific T-cell responses and decrease incidence of recurrence after surgical debulking.
To determine the safety and tolerability and recommended phase II adjuvant dosing of PRGN-2012.
Histologically confirmed diagnosis of laryngeal RRP
A history of 2 or more interventions in the last 12 months for the control of RRP
Age 18 years and older
Eastern Oncology Cooperative Group (ECOG) Performance Score of 0 or 1
This is a phase I, 3+3 dose escalation clinical trial evaluating PRGN-2012 at two dose levels (1x10^11 and 5x10^11 particle units (PU)) administered as adjuvant therapy after standard-of-care debulking surgery.
Participants will receive up to 4 separate injections of PRGN-2012 in separate limbs.
The study will enroll up to 3-6 subjects at each dose level, and 12 subjects treated at the maximum tolerated dose.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis|
|Actual Study Start Date :||March 16, 2021|
|Estimated Primary Completion Date :||October 20, 2022|
|Estimated Study Completion Date :||October 20, 2023|
Experimental: Dose Levels
Adjuvant PRGN-2012 at escalating doses
This is a phase I, 3+3 dose escalation clinical trial evaluating PRGN-2012 at two dose levels (1x10^11 and 5x10^11 particle units (PU)) administered as adjuvant therapy prior to standard-of-care debulking surgery.
- to determine the safety and tolerability and recommended phase II adjuvant dosing (RP2D) of PRGN-2012 [ Time Frame: 1 month ]The toxicities experienced by patients at each dose level will be reported per dose level. The grade as well as the type of toxicity will be tabulated per dose level. The fraction of patients who experience a DLT will be identified at a given dose level, with information reported about the number and grade of each type of DLT identified.
- Time to recurrence of papillomatous disease after completion of treatment will be recorded [ Time Frame: 1 year ]Time to recurrence of papillomatous disease after completion of treatment will be recorded. The frequency of surgery in the 12 months before or after treatment will be assessed across all treated patients for a statistically significant difference using Wilcoxon matched-pairs analysis.
- Frequency of debulking surgery during the 12 months pre and 12 months post treatment [ Time Frame: 1 year ]Time to recurrence of papillomatous disease after completion of treatment will be recorded. The frequency of surgery in the 12 months before or after treatment will be assessed across all treated patients for a statistically significant difference using Wilcoxon matched-pairs analysis.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04724980
|Contact: Erin W Ferraro, R.N.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Scott M Norberg, D.O.||National Cancer Institute (NCI)|