This study is currently recruiting participants.
Number
001572-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Fetuses;Pregnant Women
Keywords
Human Papilloma Virus; Dose Escalation; laryngotracheal disease; papillomatous disease
Recruitment Keyword(s)
None
Condition(s)
Respiratory Tract Diseases; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Tumor Virus Infections; Infections; Virus Diseases; DNA Virus Infections; Pathologic Processes; Disease Attributes; Recurrence; Papilloma; Respiratory Tract Infections; Papillomavirus Infections
Investigational Drug(s)
Bevacizumab-bvzr Bevacizumab
Investigational Device(s)
Intervention(s)
Drug: Bevacizumab
Supporting Site
National Cancer Institute
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.
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INCLUSION CRITERIA: -Age >= 18 years old. -Histologically confirmed diagnosis of RRP. -Participants must require procedure(s) to remove papillomatous disease per standard of care. -A history of 2 or more surgeries within 12 months prior to treatment initiation in order to control laryngeal and/or tracheal RRP (not required for re-treatment). -At least one of the following: --A Derkay score of 8 or greater --Measurable disease per RECIST 1.1 (participants with pulmonary RRP only) --Tracheal involvement with RRP that has required two or more clinical interventions in the last 12 months (two or more clinical interventions not required for re-treatment) --Tracheostomy. -ECOG performance status of 0-1. -Participants must have adequate organ and marrow function as defined below: --White blood cells (WBC): >2,000/microL --Absolute neutrophil count (ANC): >=1,500/microL --Hemoglobin: >9.0 g/dL --Platelets: >=100,000/microL --Total bilirubin: <=1.5 mg/dL, except in participants with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dL --Aspartate aminotransferase (AST) /Alanine aminotransferase (ALT): <=2.5 X institutional upper limit of normal (ULN) --Creatinine: within normal institutional limits OR Creatinine Clearance (CrCl): >=60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal (calculated using the Cockcroft-Gault formula). --Prothrombin time (PT) /International normalized ratio (INR) and Partial thromboplastin time (PTT): <=1 X institutional ULN. In participants on anticoagulation, coagulation tests should be within a therapeutic range. --Urinalysis: Urine dipstick < 2+ proteinuria. In participants with >=2+ proteinuria on dipstick urinalysis should undergo a 24-hour urine collection and must demonstrate <=1g of protein in 24 hours to be eligible -Participants must have received their last systemic therapy for RRP > 4 weeks or 5 half-lives, whichever is longer, prior to treatment initiation, except for systemic bevacizumab which must be > 1 year prior to treatment initiation (not applicable for re-treatment) -Individuals able to become pregnant and their partners must agree to use highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization ) for the duration of bevacizumab treatment and up to 6 months after completion of bevacizumab treatment. Note: abstinence, defined as no heterosexual sexual intercourse when this is in line with the preferred and usual lifestyle of the participant is also acceptable. -Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 6 months after bevacizumab treatment discontinuation. -All participants must have the ability to understand and willingness to sign a written informed consent. -All participants must be willing to undergo mandatory biopsy during the study. EXCLUSION CRITERIA: -History of significant (i.e., active) cardiovascular disease or thromboembolic event: cerebral vascular accident/stroke (within 6 months prior to treatment initiation), myocardial infarction (within 6 months prior to treatment initiation), unstable angina, congestive heart failure (>= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication as assessed by EKG. -History of abdominal fistula or gastrointestinal perforation within 6 months prior to treatment initiation. -Major surgery within 4 weeks prior to treatment initiation. -Non-healing wound, active ulcer, or untreated bone fracture. -History of hemoptysis (>2.5 mL of bright red blood per episode) within 1 month prior to treatment initiation. -Evidence of bleeding diathesis or significant coagulopathy (with or without current therapeutic anticoagulation). -Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to treatment initiation. -Inadequately controlled hypertension (defined as systolic blood pressure (BP) >150 mmHg and/or diastolic blood pressure > 100 mmHg), an average of 3 BP readings on 2 sessions will be used to measure blood pressure if initial reading indicates inadequately controlled hypertension. NOTE: anti-hypertensive therapy to achieve blood pressures below these parameters is allowed. -Prior history of hypertensive crisis or hypertensive encephalopathy. -Persisting toxicity related to prior therapy of Grade >1 per Common Terminology Criteria for Adverse Events (CTCAE) v 5.0. NOTE: alopecia, sensory neuropathy Grade <=2 are acceptable. -Known active alcohol or drug abuse. -History of allergy to study drug components. -Pregnancy (confirmed with Beta-Human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test in WOCBP performed at screening). -Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.
-Age >= 18 years old.
-Histologically confirmed diagnosis of RRP.
-Participants must require procedure(s) to remove papillomatous disease per standard of care.
-A history of 2 or more surgeries within 12 months prior to treatment initiation in order to control laryngeal and/or tracheal RRP (not required for re-treatment).
-At least one of the following:
--A Derkay score of 8 or greater
--Measurable disease per RECIST 1.1 (participants with pulmonary RRP only)
--Tracheal involvement with RRP that has required two or more clinical interventions in the last 12 months (two or more clinical interventions not required for re-treatment)
--Tracheostomy.
-ECOG performance status of 0-1.
-Participants must have adequate organ and marrow function as defined below:
--White blood cells (WBC): >2,000/microL
--Absolute neutrophil count (ANC): >=1,500/microL
--Hemoglobin: >9.0 g/dL
--Platelets: >=100,000/microL
--Total bilirubin: <=1.5 mg/dL, except in participants with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dL
--Aspartate aminotransferase (AST) /Alanine aminotransferase (ALT): <=2.5 X institutional upper limit of normal (ULN)
--Creatinine: within normal institutional limits
OR
Creatinine Clearance (CrCl): >=60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal (calculated using the Cockcroft-Gault formula).
--Prothrombin time (PT) /International normalized ratio (INR) and Partial thromboplastin time (PTT): <=1 X institutional ULN. In participants on anticoagulation, coagulation tests should be within a therapeutic range.
--Urinalysis: Urine dipstick < 2+ proteinuria. In participants with >=2+ proteinuria on dipstick urinalysis should undergo a 24-hour urine collection and must demonstrate <=1g of protein in 24 hours to be eligible
-Participants must have received their last systemic therapy for RRP > 4 weeks or 5 half-lives, whichever is longer, prior to treatment initiation, except for systemic bevacizumab which must be > 1 year prior to treatment initiation (not applicable for re-treatment)
-Individuals able to become pregnant and their partners must agree to use highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization ) for the duration of bevacizumab treatment and up to 6 months after completion of bevacizumab treatment. Note: abstinence, defined as no heterosexual sexual intercourse when this is in line with the preferred and usual lifestyle of the participant is also acceptable.
-Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 6 months after bevacizumab treatment discontinuation.
-All participants must have the ability to understand and willingness to sign a written informed consent.
-All participants must be willing to undergo mandatory biopsy during the study.
EXCLUSION CRITERIA:
-History of significant (i.e., active) cardiovascular disease or thromboembolic event:
cerebral vascular accident/stroke (within 6 months prior to treatment initiation), myocardial infarction (within 6 months prior to treatment initiation), unstable angina, congestive heart failure (>= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication as assessed by EKG.
-History of abdominal fistula or gastrointestinal perforation within 6 months prior to treatment initiation.
-Major surgery within 4 weeks prior to treatment initiation.
-Non-healing wound, active ulcer, or untreated bone fracture.
-History of hemoptysis (>2.5 mL of bright red blood per episode) within 1 month prior to treatment initiation.
-Evidence of bleeding diathesis or significant coagulopathy (with or without current therapeutic anticoagulation).
-Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to treatment initiation.
-Inadequately controlled hypertension (defined as systolic blood pressure (BP) >150 mmHg and/or diastolic blood pressure > 100 mmHg), an average of 3 BP readings on 2 sessions will be used to measure blood pressure if initial reading indicates inadequately controlled hypertension. NOTE: anti-hypertensive therapy to achieve blood pressures below these parameters is allowed.
-Prior history of hypertensive crisis or hypertensive encephalopathy.
-Persisting toxicity related to prior therapy of Grade >1 per Common Terminology Criteria for Adverse Events (CTCAE) v 5.0. NOTE: alopecia, sensory neuropathy Grade <=2 are acceptable.
-Known active alcohol or drug abuse.
-History of allergy to study drug components.
-Pregnancy (confirmed with Beta-Human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test in WOCBP performed at screening).
-Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.
Principal Investigator
Referral Contact
For more information: