Avelumab for People With Recurrent Respiratory Papillomatosis
Condition: Recurrent Respiratory Papillomatosis; Juvenile Laryngeal Papilloma; Laryngeal Papilloma, Recurrent; Respiratory Papillomatosis; Human Papilloma Virus
MeSH terms: Respiratory Tract Infections; Papillomavirus Infections; Papilloma; Laryngeal Neoplasms; Recurrence
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      Recurrent respiratory papillomatosis (RRP) is a rare disease caused by human papillomavirus.
      It can cause voice changes, airway compromise, pulmonary lesions, and cancers. Programmed
      death-ligand 1 (PD-L1) is a protein on cells. It may be able to stop or decrease the immune
      system s response to viruses such as human papillomavirus. The drug Avelumab interferes with
      the activity of PD-L1. Researchers want to see if Avelumab treats RRP and study its side
      effects.

      Objective:

      To see if Avelumab works in treating RRP and is safe.

      Eligibility:

      People ages 18 and older with aggressive RRP that has not responded to available treatments

      Design:

      Participants will be screened with:

      Medical history

      Previously collected tumor tissue

      Physical exam

      Blood, urine, and heart tests

      Endoscopy procedure: A small tube with a camera is used to look in the nose, throat, larynx,
      and upper windpipe.

      Before starting treatment, participants will have:

      Endoscopy under anesthesia. A sample of papilloma will be taken.

      Voice handicap questionnaire

      Computed tomography (CT) scans

      Apheresis: An intravenous (IV) is inserted into an arm vein. White blood cells are separated
      from the rest of the blood and stored for research. The rest of the blood is returned through
      the same IV or one in the other arm.

      Participants will get the study drug by IV every 2 weeks for up to 12 weeks.

      Participants will repeat the previous tests throughout the study.

      If they respond to treatment, participants will be evaluated every 6 weeks (3 times), then
      every 12 weeks (3 times), then every 26 weeks (2 times) until their disease progresses.

      Participants will be evaluated 30 days after their last infusion. They will then be contacted
      annually.
    

Detailed description: 
      Background

        -  Recurrent respiratory papillomatosis (RRP) is a rare papillomatous disease of the
           aerodigestive tract that is caused by the Human Papilloma Virus (HPV).

        -  RRP can progress to cause airway compromise, fatal pulmonary lesions, and invasive
           cancers.

        -  There is no effective systemic therapy for RRP. Patients require repeated interventional
           procedures for disease control.

        -  Study of a small number of RRP samples has shown programmed death-ligand 1 (PD-L1)
           expression by inflammatory mononuclear cells and by papilloma epithelial cells.

        -  This clinical trial will evaluate the activity of a PD-L1-targeted drug, avelumab, in
           the treatment of RRP. This drug was selected for its demonstrated activity in a variety
           of cancers and for its acceptable safety profile.

      Objective

      -Determine the complete response rate for avelumab in the treatment of patients with RRP.

      Eligibility

        -  Histologically confirmed diagnosis of RRP.

        -  One of the following:

             -  A Derkay anatomic score of 10 or greater and a history of two or more endoscopic
                interventions in the last 12 months for control of RRP.

             -  Pulmonary RRP with pulmonary disease that is measurable by computed tomography
                scan.

             -  Tracheal involvement with RRP that has required either two or more endoscopic
                interventions in the last 12 months or a tracheostomy.

        -  Age 18 years or greater.

        -  Eastern Oncology Cooperative Group Performance Score of 0 or 1.

      Design

        -  Phase II clinical trial

        -  Simon optimal two-stage design with initial enrollment of 12 patients and expansion to
           37 patients if one or more complete response(s) is/are observed in the initial patients.
    

Intervention name(s): Avelumab
Intervention type(s): Drug
Intervention description(s): Avelumab 10 mg/kg intravenous (IV) every 2 weeks for up to 6 doses.
Other intervention name(s): Bavencio
Intervention MeSH terms: Avelumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: PD-L1 Expression; Human Papilloma Virus (HPV); Juvenile-onset Disease; Papillomatous Lesions; Monoclonal Antibody