Bewacyzumab u dorosłych z nawracającą brodawczakowatością dróg oddechowych (RRP)

• INCLUSION CRITERIA:

• Age >= 18 years old.

• Histologically confirmed diagnosis of RRP.

• Individuals must require procedure(s) to remove papillomatous disease per standard of care.(not required for re-treatment)

• 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 (not required for re-treatment):

  • 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)
  • Tracheostomy.

• ECOG performance status of 0-1.

• Individuals 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

  • Individuals 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 individual is also acceptable.
  • Breastfeeding individuals must be willing to discontinue breastfeeding from study treatment initiation through 6 months after bevacizumab treatment discontinuation.
  • All individuals must have the ability to understand and willingness to sign a written informed consent.
  • All individuals must be willing to undergo mandatory biopsy during the study (not applicable for re-treatment).

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.