Avelumab for People With Recurrent Respiratory Papillomatosis

NCT02859454 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 16016016-C-0160
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

PD-L1 Expression; Human Papilloma Virus (HPV); Juvenile-onset Disease; Papillomatous Lesions; Monoclonal Antibody

Outcome Measures

Primary Outcomes (2)

• 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

  The Derkay is an objective score based on the number of sites and bulkiness of papillomas within the pharynx, larynx and trachea and a subjective score determined by voice and treating symptoms. Complete response is assessed by The Derkay Staging System which is defined as a physical exam and/or clinic-based flexible nasopharyngolaryngoscopy and/or tracheoscopy, exam under anesthesia with endoscopy and biopsies; no evidence of papillomas on physical exam and/or clinic based flexible nasopharyngolaryngoscopy and/or tracheoscopy; and no evidence of papillomas by exam under anesthesia (sedation or general anesthesia) with endoscopy and biopsies.

  Disease response was performed at 6 and 12 weeks after the first dose of Avelumab. Patients who experience a complete response will be evaluated every 6 weeks x 3, then every 12 weeks x 3, then every 26 weeks x 2 or until disease progression,up to 3 years

• 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

  Complete response is measured by The Response Criteria in Solid Tumors (RECIST) v1.1 calculated from chest CT scans. Complete response is absence of disease (e.g., lesions) by imaging.

  Disease response was performed at 6 and 12 weeks after the first dose of Avelumab. Patients who experience a complete response will be evaluated every 6 weeks x 3, then every 12 weeks x 3, then every 26 weeks x 2 or until disease progression,up to 3 years

Secondary Outcomes (5)

• Effect of Treatment With Avelumab on Voice Handicap Index-10 Score

  Baseline, 6 weeks, and 12 weeks after the first dose of Avelumab.

• 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

  Disease response was performed at 6 and 12 weeks after the first dose of Avelumab. Patients who experience a complete response will be evaluated every 6 weeks x 3, then every 12 weeks x 3, then every 26 weeks x 2 or until disease progression,up to 3 years

• 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

  Disease response was performed at 6 and 12 weeks after the first dose of Avelumab. Patients who experience a complete response will be evaluated every 6 weeks x 3, then every 12 weeks x 3, then every 26 weeks x 2 or until disease progression, up to 3 year

• Duration of Clinical Responses to Avelumab

  Disease response was performed at 6 and 12 weeks after the first dose of Avelumab. Patients who experience a complete response will be evaluated every 6 weeks x 3, then every 12 weeks x 3, then every 26 weeks x 2 or until disease progression,up to 4.5 yrs

• Number of Participants With Serious and Non-serious Adverse Events

  Date treatment consent signed to date off study, approximately 28 months and 20 days.

Study Arms (1)

Avelumab

EXPERIMENTAL

Avelumab 10 mg/kg intravenous (IV) every 2 weeks for up to 6 doses.

Drug: Avelumab

Interventions

Avelumab DRUG

Avelumab 10 mg/kg intravenous (IV) every 2 weeks for up to 6 doses.

Also known as: Bavencio

Avelumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Robbins Y, Friedman J, Clavijo PE, Sievers C, Bai K, Donahue RN, Schlom J, Sinkoe A, Hinrichs CS, Allen C, Abdul Sater H, Gulley JL, Norberg S. Dual PD-L1 and TGF-b blockade in patients with recurrent respiratory papillomatosis. J Immunother Cancer. 2021 Aug;9(8):e003113. doi: 10.1136/jitc-2021-003113.

  PMID: 34462327 DERIVED

• Allen CT, Lee S, Norberg SM, Kovalovsky D, Ye H, Clavijo PE, Hu-Lieskovan S, Schlegel R, Schlom J, Strauss J, Gulley JL, Trepel J, Hinrichs CS. Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis. J Immunother Cancer. 2019 May 3;7(1):119. doi: 10.1186/s40425-019-0603-3.

  PMID: 31053174 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Recurrent respiratory papillomatosis

Interventions

avelumab

Results Point of Contact

• Title: Scott Norberg, DO
• Organization: National Cancer Institute

scott.norberg@nih.gov

301-275-9668

Study Officials

• Scott Norberg, DO

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 6, 2016
• First Posted: August 9, 2016
• Study Start: August 6, 2016
• Primary Completion: June 30, 2018
• Study Completion: September 15, 2021
• Last Updated: November 2, 2021
• Results First Posted: May 14, 2019

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)