Use of Cidofovir for Recurrent Respiratory Papillomatosis

Phase 4

Completed

Conditions: Recurrent Respiratory Papillomatosis

Interventions: Drug: Placebo
Drug: Cidofovir

Registration Number: NCT00205374

Lead Sponsor: University of Wisconsin, Madison

Brief Summary: Recurrent respiratory papillomatosis (RRP) is the most common benign neoplasm of the larynx in the pediatric population. The impact of the disease on patients and families can be tremendous due to the need for frequent treatment. It would be highly beneficial to develop effective medical therapies as adjunctive measures to surgical ablation with the goal of reducing the frequency of reoccurrence.

Detailed Description: The focus of the present study is to evaluate the usefulness of cidofovir injection in diminishing the frequency and magnitude of papilloma recurrences in adult and pediatric RRP patients. Briefly, patients will be randomized into either a treatment (cidofovir injection) or a placebo group. The following measures will be made at each of 6 data collection time points, over the course of one year: (1) tumor load, based upon a published staging system for papilloma, (2) degree of respiratory obstruction for phonation, as assessed by phonation threshold pressures, and (3) general health, on validated health inventories (SF12 and Voice Handicap Index for adults; PedsQL (Trademarked) for children) and via measures of height weight and days absent from school or daycare, where applicable, for children. A repeated measures analysis will allow examination of time by treatment interactions to determine if the cidofovir injection group has fewer, or less severe, recurrences than the placebo group.

Specifically, we will answer the following questions in this investigation:

1. Does cidofovir injection reduce the frequency of RRP recurrences?

2. Does cidofovir injection reduce the magnitude of RRP, as assessed with a proposed staging system for RRP (Derkay et al., 1998) and measures of phonatory threshold pressure?

3. Does cidofovir injection improve general health, as assessed by height, weight and days absent from school in pediatric patients and health inventories (general health and voice-related) in children and adults?

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

Inclusion Criteria

4 surgeries for RRP in last 12 months

Exclusion Criteria

Renal insufficiency
Nephrotoxic drugs in the last 7 days
Sulfa allergies
Currently treated with systemic or topical HPV chemotherapeutic agents
Females of childbearing potential with a positive pregnancy test
Women who are breast feeding

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	On the baseline study day, patients will be randomized into either a treatment group (cidofovir injection) or a placebo group. A restricted randomization procedure, in groups of 4, will be used to encourage uniformity in sample sizes between groups.
Cidofovir	Cidofovir	Cidofovir (Vistide) is a commercially available agent approved by the FDA for the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). The drug is not FDA approved for the treatment of RRP at this time. However, recent case reports have been encouraging with regard to the effectiveness of the agent in the treatment of RRP. The FDA has granted this study a "safe to proceed" designation with IND 58,481.

Primary Outcome Measures

Name	Time	Method
Change in Papilloma Severity	Baseline, 2 months, and 12 months	Derkay Severity Score. Minimum Score is Zero. Maximum score is 86. Treatment of RRP with cidofovir injection will be considered efficacious if drug group patients experience clinically or statistically significant changes in papilloma severity and inter-surgery time intervals (relative to pre-treatment assessments), when compared with placebo group patients. The scale rates - Voice (normal 0, abnormal 1, aphonic 2) Stridor (absent 0, present with activity 1, present at rest 2) Urgency of the intervention (scheduled 0, elective 1, urgent 2, emergent 3) Respiratory distress (none 0, mild 1, mod 2, severe 3, extreme 4). For multiple anatomical sites (18 or more) in the upper airway, left and right sides, lesions are rated as 0=none, 1=surface lesion, 2=raised lesion, and 3=bulky lesion). A higher rating value indicates more advanced disease and a worse outcome.

Secondary Outcome Measures

Name	Time	Method
12-month Change in Voice Handicap Index (VHI) Score	2 months, and 12 months	Voice Handicap Index. This scale rates a patient's perception of voice related handicap in the domains of functional, physical, and emotional. There are 10 questions for each domain. Each question is rated by the subject on a 5-point scale, never =0, almost never =1, sometimes =2, almost always =3, always =4). A lower total score or domain score indicates improved, or less, voice handicap. Thus, the maximum total score is 4 X 30 = 120. For each domain, the maximum score is 4 X 10 = 40. Scores of 0 are the lowest possible score. In the paper we say that the Maximum score is 100, but obviously is it actually 120. Complete scale = 0-120. Lower score indicates improved perceived voice-realted quality of life.