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
Intervention: Avelumab
Intervention description: Avelumab 10 mg/kg intravenous (IV) every 2 weeks for up to 6 doses.
Intervention MeSH terms: Avelumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: PD-L1 Expression; Human Papilloma Virus (HPV); Juvenile-onset Disease; Papillomatous Lesions; Monoclonal Antibody

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Recurrent Respiratory Papillomatosis (RRP) CRITERIA:

          -  Histological diagnosis of RRP confirmed by pathology report from a Clinical Laboratory
             Improvement Amendments (CLIA)-certified laboratory.

             -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.

               -  Greater than or equal to 18 years of age.

               -  Able to understand and sign the Informed Consent Document.

               -  Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.

               -  Willing to undergo endoscopic evaluation with biopsies in compliance with this
                  protocol.

               -  No systemic therapy for RRP for four weeks prior to treatment.

               -  Screening laboratory values must meet the following criteria and should be
                  obtained within 14 days prior to first dose:

          -  White blood cells (WBC) > 2000/microL

          -  Neutrophils > 1500/microL

          -  Platelets > 100 times10(3)/microL

          -  Hemoglobin > 9.0 g/dL

          -  Serum creatinine < 1.5 times upper limit of normal (ULN) or creatinine clearance
             (CrCl) > 30 mL/min (measured or calculated using the Cockcroft-Gault formula below):

               -  Female CrCl: (140 - age in years) times weight in kg x 0.85/72 times serum
                  creatinine in mg/dL

               -  Male CrCl: (140 - age in years) times weight in kg x 1.00/72 times serum
                  creatinine in mg/Dl

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than or equal to
             2.5 times ULN; for subjects with documented metastatic disease to theliver, AST and
             ALT levels less than or equal to 5 times ULN

          -  Total Bilirubin less than or equal to 1.5 times ULN

               -  Sexually active subjects (men and women) and all subjects of reproductive
                  potential must agree to use two methods of contraception: one highly effective
                  and one other effective method for at least 28 days prior, throughout the
                  avelumab treatment and for at least 60 days after avelumab treatment. Highly
                  Effective Methods are defined as: Intrauterine device (IUD), hormonal (birth
                  control pills, injections, implants), tubal ligation and partners vasectomy;
                  Other Effective Methods are defined as: latex condom, diaphragm and cervical cap.

               -  Seronegative for human immunodeficiency virus (HIV) antibody. The experimental
                  treatment being evaluated in this protocol depends on an intact immune system.
                  Patients who are HIV seropositive can have decreased immune function and thus are
                  likely less responsive to the experimental treatment.

               -  Seronegative for hepatitis B antigen, positive hepatitis B tests can be further
                  evaluated by confirmatory tests (Hep B deoxyribonucleic acid (DNA) Quantification
                  (Quant), HBV Viral Load), and if confirmatory tests are negative, the patient can
                  be enrolled.

               -  Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C
                  antibody test is positive, then patients must be tested for the presence of
                  antigen by Hep C RNA Quant, Hepatitis C Virus (HCV) Viral Load and be HCV
                  ribonucleic acid (RNA) negative.

        EXCLUSION CRITERIA:

          -  Any severe acute or chronic medical or psychiatric conditions including recent (within
             the past year) or active suicidal ideation or behavior; liver, lung disease (with the
             exception of what is specified in inclusion criteria above), or laboratory
             abnormalities that, in the opinion of the investigators, may increase the risk
             associated with study participation or study drug administration, impair the ability
             of the subject to receive protocol therapy, or interfere with the interpretation of
             study results and in the judgment of the investigator, would make the patient
             inappropriate for entry into this study. Patients with mild to moderate asthma or
             chronic obstructive pulmonary disease (COPD) well controlled with oral or inhaled
             medications are permitted to enroll.

          -  Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
             residual hypothyroidism due to autoimmune condition only requiring hormone
             replacement, or psoriasis not requiring systemic treatment, are permitted to enroll.

          -  Subjects with a condition requiring systemic treatment with either corticosteroids (>
             10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
             days of study drug administration. Inhaled, topical intranasal or intro-ocular
             steroids, and adrenal replacement doses <10 mg daily prednisone equivalents are
             permitted in the absence of active autoimmune disease.

          -  Prior organ transplantation, including allogeneic stem cell transplantation.

          -  Prior treatment with an anti-programmed death-ligand 1 (PD-1), anti-PD-L1,
             anti-programmed death-ligand 2 (PD-L2), anti-cytotoxic T-lymphocyte associated protein
             4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell
             co-stimulation or immune checkpoint pathways.

          -  Patients who are receiving any other investigational agents

          -  Pregnant or breast feeding. Women of childbearing potential must have a negative
             pregnancy test at screening. Women of childbearing potential include women who have
             experienced menarche and who have not undergone successful surgical sterilization
             (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not
             postmenopausal. Post-menopause is defined as amenorrhea greater than or equal to 12
             consecutive months. Note: women who have been amenorrheic for 12 or more months are
             still considered to be of childbearing potential if the amenorrhea is possibly due to
             prior chemotherapy, anti-estrogens, ovarian suppression or any other reversible
             reason.

          -  History of allergy to study drug components.

        History of severe hypersensitivity reaction to any monoclonal antibody (Grade greater than
        or equal to 3 National Cancer Institute (NCI)-Common Terminology Criteria in Adverse Events
        (CTCAE) v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more
        features of partially controlled asthma).

          -  Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
             accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months
             prior to enrollment), unstable angina, congestive heart failure (greater than or equal
             to New York Heart Association Classification Class II), or serious cardiac arrhythmia
             requiring medication.

          -  Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however,
             alopecia, sensory neuropathy Grade less than or equal to 2 or other Grade less than or
             equal to 2 adverse events (AEs) not constituting a safety risk based on investigator's
             judgment are acceptable.

          -  Known alcohol or drug abuse.

          -  Vaccination within 4 weeks of the first dose of avelumab and while on trial is
             prohibited except for administration of inactivated vaccines.