Phase 2 N=13 Treatment

Avelumab for People With Recurrent Respiratory Papillomatosis

Recurrent Respiratory Papillomatosis · Juvenile Laryngeal Papilloma · Laryngeal Papilloma, Recurrent · Respiratory Papillomatosis · Human Papilloma Virus

Bottom Line

View on ClinicalTrials.gov: NCT02859454 ↗

Enrolled (actual)

Serious AEs

15.4%

Results posted

May 2019

Primary outcome: Primary: Number of Patients With Laryngotracheal Recurrent Respiratory Papillomatosis (RPP) Who Achieve a Complete Response With Avelumab as Measured by Derkay Score Calculated From Clinical Endoscopy — 0 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Avelumab (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Jun 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Patients With Laryngotracheal Recurrent Respiratory Papillomatosis (RPP) Who Achieve a Complete Response With Avelumab as Measured by Derkay Score Calculated From Clinical Endoscopy	—	—
PRIMARY Number of Patients With Pulmonary Recurrent Respiratory Papillomatosis (RPP) Who Achieve a Complete Response With Avelumab as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Calculated From Chest Computed Tomography (CT) Scans	—	—
SECONDARY Effect of Treatment With Avelumab on Voice Handicap Index-10 Score	26; 22; 23; 9; 12; 3	—
SECONDARY Number of Patients With Laryngotracheal Recurrent Respiratory Papillomatosis (RPP) Who Achieve a Partial Response With Avelumab as Measured by Derkay Score Calculated From Clinical Endoscopy	6	—
SECONDARY Number of Patients With Pulmonary Recurrent Respiratory Papillomatosis (RPP) Who Achieve a Partial Response With Avelumab as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Calculated From Chest Computed Tomography (CT) Scans	—	—
SECONDARY Duration of Clinical Responses to Avelumab	14.7	—
SECONDARY Number of Participants With Serious and Non-serious Adverse Events	13	—

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 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 vitili

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Data sourced from ClinicalTrials.gov (NCT02859454). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.