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Trial record 1 of 1 for:    NCT02859454.
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Avelumab for People With Recurrent Respiratory Papillomatosis

This study is currently recruiting participants.
See Contacts and Locations
Verified May 30, 2017 by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT02859454
First received: August 6, 2016
Last updated: June 30, 2017
Last verified: May 30, 2017
  Purpose

Background:

Recurrent respiratory papillomatosis (RRP) is a rare disease caused by human papillomavirus. It can cause voice changes, airway compromise, pulmonary lesions, and cancers. 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

CT scans

Apheresis: An 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.


Condition Intervention Phase
Recurrent Respiratory Papillomatosis Juvenile Laryngeal Papilloma Laryngeal Papilloma, Recurrent Respiratory Papillomatosis Human Papilloma Virus Drug: Avelumab Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase II Study of Avelumab in Subjects With Recurrent Respiratory Papillomatosis

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):

Primary Outcome Measures:
  • Complete response rate [ Time Frame: End of treatment ]

Secondary Outcome Measures:
  • Effect of treatment with avelumab on Derkay and Voice Handicap Index-10 scores [ Time Frame: End of treatment ]
  • Partial response rate for avelumab [ Time Frame: End of treatment ]
  • Duration of clinical responses to avelumab [ Time Frame: Time to progression ]

Estimated Enrollment: 40
Study Start Date: August 4, 2016
Estimated Study Completion Date: June 30, 2023
Estimated Primary Completion Date: June 30, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Avelumab 10 mg/kg IV every 2 weeks for up to 6 doses.
Drug: Avelumab
Avelumab 10 mg/kg IV every 2 weeks for up to 6 doses.

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 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.
  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

RRP CRITERIA:

  • Histological diagnosis of RRP confirmed by pathology report from a 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 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:
  • WBC > 2000/microL
  • Neutrophils > 1500/microL
  • Platelets > 100 times10(3)/microL
  • Hemoglobin > 9.0 g/dL
  • Serum creatinine < 1.5 times 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
  • AST/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 partner s vasectomy; Other Effective Methods are defined as: latex condom, diaphragm and cervical cap.
    • Seronegative for 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 DNA 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, HCV Viral Load and be HCV 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-PD-1, anti-PD-L1, anti-PD-L2, anti-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 NCI-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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02859454

Contacts
Contact: Erin W Ferraro, R.N. (240) 760-6163 erin.ferraro@nih.gov

Locations
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      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Christian S Hinrichs, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02859454     History of Changes
Other Study ID Numbers: 160160
16-C-0160
Study First Received: August 6, 2016
Last Updated: June 30, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
PD-L1 Expression
Human Papilloma Virus (HPV)
Juvenile-onset Disease
Papillomatous Lesions
Monoclonal Antibody

Additional relevant MeSH terms:
Papilloma
Respiratory Tract Infections
Papillomavirus Infections
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Infection
Respiratory Tract Diseases
DNA Virus Infections
Virus Diseases
Tumor Virus Infections

ClinicalTrials.gov processed this record on July 24, 2017