Bevacizumab in Adults With Recurrent Respiratory Papillomatosis (RRP)
- Conditions
- Respiratory Tract DiseasesTumor Virus InfectionsPathologic ProcessesDisease AttributesRecurrenceNeoplasmsInfectionsNeoplasms, Squamous CellVirus DiseasesNeoplasms by Histologic Type
- Interventions
- Registration Number
- NCT05797246
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Background:
Recurrent respiratory papillomatosis (RRP) is a rare disease that causes wart-like growths in the airways. These growths come back when removed; some people may need 2 or more surgeries per year to keep their airways clear. Better treatments are needed.
Objective:
To see if a drug called bevacizumab can reduce the number of surgeries needed in people with RRP.
Eligibility:
People aged 18 and older with recurrent RRP; they must need surgery to remove the growths in their airways.
Design:
Participants will be screened. Their ability to breathe and speak will be evaluated. They will have an endoscopy: a flexible tube with a light and camera will be inserted into their nose and throat. They will have a test of their heart function and imaging scans of their chest.
Participants will have surgery to remove the growths in their airways.
Bevacizumab is given through a small tube placed in a vein in the arm. After the surgery, participants will receive 11 doses of this drug: every 3 weeks for 3 doses, and then every 6 weeks for 8 more doses. They will come to the clinic for each dose; each visit will be about 8 hours.
Tissue samples of the growths will be collected after the second treatment; this will be done under general anesthesia.
Participants may undergo apheresis: Blood will be drawn from a needle in an arm. The blood will pass through a machine that separates out the cells needed for the study. The remaining blood will be returned to the body through a second needle.
Follow-up will continue for 1 year after the last treatment.
- Detailed Description
Background:
* Recurrent respiratory papillomatosis (RRP) is a rare papillomatous disease of the respiratory tract that is caused by Human Papilloma Virus (HPV) types 6 or 11.
* RRP can progress to cause severe voice disturbance, airway compromise, fatal pulmonary lesions, and rarely invasive cancers.
* There is no approved systemic therapy for RRP. Participants require repeated surgical procedures for disease debridement and control.
* Translational research studies have shown high levels of vascularity in papilloma tissue driven in part by high levels of vascular endothelial growth factor (VEGF)-A mRNA, vascular endothelial growth factor receptors (VEGFR)-1 and VEGFR-2 and elevated serum levels of VEGF-A, particularly in cases of aggressive RRP.
* Papillomas are also infiltrated by immunosuppressive myeloid and regulatory T-cells.
* Systemic inhibition of VEGF signaling may reduce VEGF-driven angiogenesis in papillomas and reduce chemotaxis and expansion of immunosuppressive myeloid cells and regulatory T-cells.
* Bevacizumab is a recombinant humanized monoclonal antibody that binds all active forms of VEGF-A.
* Bevacizumab is FDA approved for the treatment of metastatic colorectal cancer, non-small cell lung cancer, metastatic renal cell carcinoma, recurrent glioblastoma, cervical cancer, epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer and was selected for its demonstrated activity in a variety of cancers and for its acceptable safety profile.
* Use of systemic bevacizumab in patients with severe and/or tracheal RRP has not been studied prospectively in controlled clinical studies, but clinical safety and activity has been reported in retrospective single institution case series.
* Bevacizumab resistance can develop in cancer patients due to a variety of tumor escape mechanisms that are unlikely to occur in RRP patients with normal endothelial cells, but bevacizumab re-treatment for recurrent RRP has not been evaluated in controlled clinical studies.
Objective:
-To determine the percentage of participants with an increase in their surgery-free interval during treatment with systemic bevacizumab
Eligibility:
* Histologically confirmed diagnosis of RRP
* A history of 2 or more surgeries in the last 12 months in order to control laryngeal and/or tracheal RRP
* At least one of the following:
* A Derkay score of 8 or greater
* Pulmonary RRP with disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Tracheal involvement with RRP that has required two or more clinical interventions in the last 12 months
* Tracheostomy
* Age \>=18 years old
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
Design:
* This is a phase II, single arm clinical trial evaluating systemic bevacizumab.
* Participants will receive bevacizumab (10 mg/kg IV) every three weeks for 3 cycles and then every 6 weeks for a total treatment course of 11 cycles for approximately 1 year total.
* Operative examination under anesthesia (EUA) with biopsies for research and possible papilloma debulking for safety will be performed before dose 1, optional EUA for research biopsies may be performed following dose 2 and at cycles 6 and 11.
* Participants may undergo standard-of-care operative EUA with papilloma cleanout during the 1-year treatment period as clinically indicated at the NIH.
* The mean surgery-free interval during the 1-year treatment period will be compared to the mean surgery-free interval in the 12 months prior to treatment.
* Participants will also be assessed for papilloma recurrence and surgery-free interval at 6, 12, 24 weeks and every 3 months after that until 1 year following completion of treatment.
* A total of 20 evaluable participants will be treated on study.
* During the follow up period, up to 15 participants who develop sufficient papilloma recurrence to require a clinical intervention may be re-treated with 11 additional cycles of bevacizumab (10 mg/kg IV) following the same schedule as the initial treatment.
* Prior to the initiation of re-treatment, an optional operative EUA with biopsies for research and possible papilloma debulking for safety may be performed.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1 Bevacizumab Bevacizumab treatment course
- Primary Outcome Measures
Name Time Method To determine the percentage of participants with an increase in their surgery-free interval during treatment with systemic bevacizumab. 1 year Determined by measuring the mean duration between successive clinically indicated surgeries in the 12 months during treatment for that participant and determining whether that duration is longer than the mean duration between successive clinically indicated surgeries in the 12 months prior to treatment by one month or more. This fraction of participants who are classified as having a success will be reported along with a 95% confidence interval.
- Secondary Outcome Measures
Name Time Method The safety of systemic bevacizumab in participants with aggressive RRP 42 days after the study agent was last administered Evaluation of safety will be done as follows: each participant will be evaluated for safety and toxicity, and the fraction of participants experiencing AEs will be reported by type and grade of AE
Recurrence free interval after treatment Weeks 6, 12, 24 and remote assessment (if needed) Time to recurrence of papillomatous disease after completion of treatment will be recorded and reported descriptively.
Rate of pulmonary RRP partial response (PR) and complete response (CR) by RECIST 1.1 in participants with pulmonary disease. 6 weeks after completion of treatment The fraction of participants with a pulmonary RRP partial response and a pulmonary RRP complete response will be reported in all treated pulmonary participants, along with 95% confidence intervals for each.
The rate of papilloma regrowth by determining the percentage of participants with an increase in their surgery-free interval after treatment with systemic bevacizumab Weeks 6, 12, 24 after completion of treatment, every 3 months after that with the last evaluation performed at 1 year after completion of study treatment The rate of papilloma regrowth will be determined by measuring the mean duration between successive clinically indicated surgeries in the 12 months after treatment for that participant and determining whether that duration is longer than the mean duration between successive clinically indicated surgeries in the 12 months prior to treatment by one month or more. This fraction of participants who are classified as having a success will be reported along with a 95% confidence interval.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States