Bevacizumab for Treatment of Recurrent Respiratory Papillomatosis (RRP)
Condition: Recurrent Respiratory Papillomatosis
MeSH terms: Respiratory Tract Infections; Papillomavirus Infections; Papilloma; Recurrence
Intervention: Avastin® (bevacizumab); Saline
Intervention description: Bevacizumab injections (~7.5-12.5mg in 0.3 - 0.5 c.c.) into diseased vocal folds in conjunction with 532 nm pulsed-KTP laser photoangiolysis, administered every 6 ±1 weeks, for a total of 5 treatments. No patient will have an injection volume exceed 0.5 cc. for any single treatment. If initial results indicate a benefit, as described below, an extension of the active treatment period will be permitted up to a total treatment duration of 18 months.; A sham injection with saline (0.3-0.5 cc) has been administered to the other vocal fold as the control. This therapy will be administered once every 6 ± 1 week for 6 months, with the same vocal fold selected for the initial treatment always getting the drug injection.
Intervention MeSH terms: Bevacizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      This phase I single center open labeled study is planned to assess the safety and
      tolerability of bevacizumab for treating patients with bilateral Recurrent Respiratory
      Papillomatosis (RRP). Approximately 20 patients will receive bevacizumab directly injected
      into the vocal folds. Patients who enroll in the protocol will be injected with bevacizumab
      in one vocal fold that represents the more diseased of the two folds. A sham injection with
      saline will be administered to the other vocal fold as the control. This therapy will be
      administered once every 6 ± 1 week for 6 months, with the same vocal fold selected for the
      initial treatment always getting the drug injection. The investigator will also treat lesions
      by laser photoangiolysis of both vocal folds using the 532 nm potassium-titanyl-phosphate
      (KTP) laser.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients with dysphonia that have been diagnosed with Recurrent
             Respiratory Papillomatosis (RRP) of the vocal folds

          -  Age between 18 and 60 years old

          -  Female patients must be surgically sterilized, postmenopausal, or employ adequate
             contraception. Criteria for menopause are surgical menopause (hysterectomy,
             oophorectomy) or age > 45 years with absence of menses for greater than 12 months and
             an elevated serum Hormone, follicle-stimulating (FSH) (> 25 mIU/mL). Tubal ligation
             with menses within the past 12 months is not considered to be surgical sterilization.

          -  Have bilateral glottal papillomatosis (i.e., involving both the right and left vocal
             folds)

          -  Willing and able to comply with the investigational nature of the study and able to
             communicate well with investigators.

          -  Ability to comprehend and willingness to provide written informed consent in
             accordance with institutional and regulatory guidelines.

        Exclusion Criteria:

          -  Have known sensitivity to bevacizumab

          -  Have been treated systemically with bevacizumab within 4 months (approximately 6
             half-lives).

          -  Have hematocrits < 30, elevated PT or PTT levels more than 1.2 X the upper limit of
             normal (ULN) or absolute platelet counts below the lower limit of normal (LLN).

          -  Have absolute neutrophil counts below 1500

          -  Have urine dipsticks positive for ≥3+ proteinuria will have spot urine collections and
             those patients with urine protein to urine creatinine ratios greater than 1.5.

          -  Have a history of congestive heart failure, angina that remains symptomatic despite
             medications, myocardial infarction or coronary artery disease-related procedure within
             the past 6 months (including angioplasty, stent placement, bypass graft surgery) or
             who have prosthetic heart valves.

          -  Have significant uncontrolled hypertension (systolic blood pressure above 160 and/or
             diastolic blood pressure above 100).

          -  Have had surgeries within 1 month of enrollment or who have un-healed surgical
             incisions at screening.

          -  Have a history of thromboembolic events, gastro-intestinal (GI) ulcer or bleeding, or
             with a history of wound dehiscence.

          -  Female patients that are pregnant, nursing or plan to nurse during the up to 18 months
             of treatment period.

          -  Patients with a history of bleeding disorders, documented platelet dysfunction,
             current use of anti-platelet drugs, or abnormal prothrombin time (PT) or activated
             partial thromboplastin timea (PTT) laboratory values as defined in number 3 above.