Recurrent Respiratory Papillomatosis
Conditions
Brief 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.
Interventions
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.
DRUGSaline
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.
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Activity Variable Was the Recurrence of Recurrent Respiratory Papillomatosis (RRP) in Bevacizumab Treated and the Un-treated Vocal Fold in the Same Patient During and at the End of the 6-month Treatment Period. | 6 months | Prior to each treatment,the area of reappearance of disease was measured and the % change from baseline was calculated. The change was then added to the % change from the previous treatment to generate a cumulative total % change of reappearance of RRP from baseline. The additive nature of this parameter resulted in % greater than 100% if the area of vocal fold affected by the RRP increased over the baseline measurement. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group Avastin Subjects received Avastin in the more diseased vocal fold and saline in the other. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Group Avastin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age Continuous | 47.5 years STANDARD_DEVIATION 8.6 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
The Primary Activity Variable Was the Recurrence of Recurrent Respiratory Papillomatosis (RRP) in Bevacizumab Treated and the Un-treated Vocal Fold in the Same Patient During and at the End of the 6-month Treatment Period.
Prior to each treatment,the area of reappearance of disease was measured and the % change from baseline was calculated. The change was then added to the % change from the previous treatment to generate a cumulative total % change of reappearance of RRP from baseline. The additive nature of this parameter resulted in % greater than 100% if the area of vocal fold affected by the RRP increased over the baseline measurement.
Time frame: 6 months
Population: All subjects were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bevacizumab Treated Vocal Fold | The Primary Activity Variable Was the Recurrence of Recurrent Respiratory Papillomatosis (RRP) in Bevacizumab Treated and the Un-treated Vocal Fold in the Same Patient During and at the End of the 6-month Treatment Period. | 85.3 total percentage change | Standard Deviation 68.6 |
| Untreated Vocal Fold | The Primary Activity Variable Was the Recurrence of Recurrent Respiratory Papillomatosis (RRP) in Bevacizumab Treated and the Un-treated Vocal Fold in the Same Patient During and at the End of the 6-month Treatment Period. | 225.3 total percentage change | Standard Deviation 191.1 |