Effect of Ranibizumab on Malignant Conjunctival Neoplasia

Phase 1

Completed

Brief Summary: The purpose of this study is to test the safety and tolerability of subconjunctival injection of ranibizumab in the treatment of malignant conjunctival neoplasia using the incidence and severity of adverse events.

Our secondary objective is to assess the efficacy of ranibizumab treatment on malignant conjunctival neoplasia by evaluating tumor destruction or reduction as documented by slit-lamp photography and ultrasonographic imaging and the regression of blood vessels.

Detailed Description: Ranibizumab is a recently approved vascular endothelial growth factor (VEGF) inhibitor shown to be effective in treating exudative macular degeneration. Its analog, Avastin has also been employed to treat macular edema, proliferative diabetic retinopathy and wet age related macular degeneration. Ranibizumab binds to and inhibits vascular endothelial growth factor A (VEGF-A), which has been shown to cause neovascularization and leakage in models of ocular angiogenesis. Binding to VEGF-A prevents ranibizumab's interaction with VEGFR-1 and -2 receptors on the surface of endothelial cells, thereby reducing proliferation, vascular leakage, and angiogenesis.

Given that conjunctival tumors require the formation of new blood vessels to supply the proliferating cells, we propose a study to evaluate the effect of subconjunctival ranibizumab as a primary intervention in patients with conjunctival tumors.

Recruitment & Eligibility

Inclusion Criteria

Ability to provide written informed consent and comply with study assessments for the full duration of the study
Age > 21 years
Tumors whose treatment with standard therapy would cause significant visual morbidity
Diagnosis of biopsy proven malignant conjunctival neoplasia and are
Recurrent disease
Multi-focal disease
Diffuse disease

Exclusion Criteria

Extension of tumor into eye or orbit.
Regional spread or metastatic disease
Pregnancy (positive pregnancy test) or lactation.
Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.
Current infection or inflammation in either eye
Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
Participation in another simultaneous medical investigation or trial

Arm && Interventions

Group	Intervention	Description
Subconjunctival ranibizumab	ranibizumab	Patients will receive subconjunctival ranibizumab every 2-4 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Patients Assessed for Safety and Tolerability	2 years	To test the safety and tolerability of subconjunctival injection of ranibizumab in the treatment of malignant conjunctival neoplasia - using comparative slit lamp examination \[anterior segment and ocular adnexal examination for adverse events (eg abrasion, melting), visual acuity (number of patients with decrease in visual acuity), and blood pressure at each visit (number of patients with increased blood pressure from baseline), and monthly urinalyis (number of patients with abnormal protein level in urine).

Secondary Outcome Measures

Name	Time	Method
Evaluating Tumor Destruction or Reduction	2 years	To evaluate the efficacy of treatment using comparative slit lamp examinations (anterior segment and ocular adnexal exam) to evaluate tumor volume, from baseline to month 12, and 24. To report on the number of patients with improvement in tumor volume.