Avelumab for People With Recurrent Respiratory Papillomatosis
- Conditions
- Recurrent Respiratory PapillomatosisJuvenile Laryngeal PapillomaRespiratory PapillomatosisLaryngeal Papilloma, RecurrentHuman Papilloma Virus
- Interventions
- Registration Number
- NCT02859454
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 13
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Avelumab Avelumab Avelumab 10 mg/kg intravenous (IV) every 2 weeks for up to 6 doses.
- Primary Outcome Measures
Name Time Method 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 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 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.
- Secondary Outcome Measures
Name Time Method 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 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.
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 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.
Effect of Treatment With Avelumab on Voice Handicap Index-10 Score Baseline, 6 weeks, and 12 weeks after the first dose of Avelumab. 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.
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 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.
Number of Participants With Serious and Non-serious Adverse Events Date treatment consent signed to date off study, approximately 28 months and 20 days. 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.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States