Recurrent Respiratory PapillomatosisPhase 2NCT02859454
Avelumab for People With Recurrent Respiratory Papillomatosis
A Phase 2 study testing Avelumab in people with Recurrent Respiratory Papillomatosis and Juvenile Laryngeal Papilloma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Recurrent Respiratory Papillomatosis, Juvenile Laryngeal Papilloma, Laryngeal Papilloma, Recurrent
- What is being tested?
- Avelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Aug 2016to 15 Sep 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase II Study of Avelumab in Subjects With Recurrent Respiratory Papillomatosis
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.
Read more
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.
Read the 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.
- Conditions
- Recurrent Respiratory Papillomatosis, Juvenile Laryngeal Papilloma, Laryngeal Papilloma, Recurrent, Respiratory Papillomatosis, Human Papilloma Virus
- Being tested
- Avelumab
- Keywords
- PD-L1 Expression, Human Papilloma Virus (HPV), Juvenile-onset Disease, Papillomatous Lesions, Monoclonal Antibody
- Medical subject headings
- Recurrent respiratory papillomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabDrug
Also called Bavencio
Avelumab 10 mg/kg intravenous (IV) every 2 weeks for up to 6 doses.
| Study group | Role | What they receive |
|---|---|---|
| Avelumab | Experimental | Avelumab 10 mg/kg intravenous (IV) every 2 weeks for up to 6 doses. Receives: Drug: Avelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
The Voice Handicap Index-10 questionnaire (as measured by derkay score) consists of 10 questions and determines whether a participant has a voice handicap. The scoring options for each question range from 0 (for never) to 4 (for always). The total scores (combined value from all 10 questions) range from 0 - 40. Higher scores represent a worse voice handicap. Lower scores represent a less voice handicap.
Measured: 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
Partial response is assessed by flexible nasopharyngolaryngoscopy and/or tracheoscopy using the Derkay staging system if the patient does not have pulmonary disease. 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. Partial response is a decrease in Derkay anatomic score of 30% or greater.
Measured: 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
Partial response assessed by imaging using RECIST v1.1. is defined as a ≥ 30% decrease in the sum of the longest diameters of target lesions compared with baseline.
Measured: 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
The duration of clinical responses to Avelumab is calculated from the protocol end of treatment endoscopic debulking to the next clinically indicated endoscopic debulking procedure.
Measured: 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
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Measured: Date treatment consent signed to date off study, approximately 28 months and 20 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2016 (estimated)
- Study start6 Aug 2016
- Primary completion30 Jun 2018
- Study completion15 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Recurrent Respiratory PapillomatosisStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Scott Norberg, D.O., National Cancer Institute (NCI)
- Investigators
- Scott Norberg, DO, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02859454
- Sponsor's protocol ID
- 160160
- Other IDs
- 16-C-0160
- Status last verified
- Nov 2021
- First submitted
- 6 Aug 2016
- Last updated
- 2 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34462327Allen 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.
PubMed 31053174
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Avelumab in Subjects With Recurrent Respiratory Papillomatosis
- ClinicalTrials.gov ID
- NCT02859454
- Acronym / sponsor ID
- 160160
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 6 Aug 2016 (actual)
- Primary completion
- 30 Jun 2018 (actual)
- Study completion
- 15 Sep 2021 (actual)
- First posted
- 9 Aug 2016 (estimated)
- Results
- Posted 14 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Avelumab | Experimental | Drug: AvelumabAvelumab 10 mg/kg intravenous (IV) every 2 weeks for up to 6 doses. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Histological diagnosis of RRP confirmed by pathology report from a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
- 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.
- White blood cells (WBC) > 2000/microL
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvelumabAlso: BavencioAvelumab 10 mg/kg intravenous (IV) every 2 weeks for up to 6 doses. | Drug | Avelumab |
Primary outcome
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
Time frame: 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
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.
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
Time frame: 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
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.
5 secondary outcomes
Effect of Treatment With Avelumab on Voice Handicap Index-10 Score
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Date treatment consent signed to date off study, approximately 28 months and 20 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34462327Robbins 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.
- Derived from this study: PubMed 31053174Allen 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruitingPhase 1/2
Efficacy of Booster Injection With Gardasil-9 Vaccine on Intersurgical Interval* for Adults With Recurrent Respiratory Papillomatosis*
Recurrent Respiratory Papillomatosis (RRP)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Norberg, DO principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avelumab in people with Recurrent Respiratory Papillomatosis and Juvenile Laryngeal Papilloma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02859454, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2021.