Clinical trial NCT01460810: Safety and Efficacy of Silicone Oil Tamponade for Surgical Attenuation of Radiation Damage in Choroidal Melanoma
Official title: A Prospective Pilot Study of Surgical Radiation Shielding With Vitrectomy & Silicone Oil Tamponade for the Protection of Radiation-induced Ocular Injury in the Treatment of Choroidal Melanoma With Radioactive Iodine-125 Plaque Brachytherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Choroidal Melanoma
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2011-10-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: A prospective, experimental, case series of 20 patients, with choroidal melanoma, in which pars plana vitrectomy and Silicone oil as vitreous substitute will be used as intraocular shielding for attenuating the deleterious effects of radiation dose delivered to healthy ocular tissue during Iodine-125 plaque brachytherapy treatment and assess if the treatment can reduce the incidence and severity of radiation-induced adverse effects like radiation retinopathy and permanent loss of vision.

Detailed description: Melanoma arising from the choroid and ciliary body is the most common primary intraocular cancer. The Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of I-125 brachytherapy versus enucleation for medium-sized choroidal melanoma (2.5-10.0 mm in thickness and ≤ 16 mm in diameter) showed that, for patients who met the eligibility criteria, there was no statistically significant difference in all-cause mortality between I-125 brachytherapy and enucleation 5, 10, and 12 years following treatment. The COMS trial supported the use of globe-conserving I-125 brachytherapy. Following brachytherapy, however, visual acuity in the treated eye generally declined at a rate of approximately 2 lines of visual acuity per year and nearly 45% of patients lost ambulatory vision (≤20/200) in the treated eye by 3 years.

Adverse effects of plaque brachytherapy include cataract, radiation-associated proliferative retinopathy, maculopathy and papillopathy. Radiation maculopathy, which may result in decreased central vision, cystoid macular edema (CME), macular ischemia, and chorioretinal atrophy, was reported in other series in 18% to 43% of treated eyes within 5 years after brachytherapy. Typical onset occurred 18-24 months following treatment. Primary risk factors for radiation papillopathy and maculopathy were total radiation dose to the affected structures, proximity of the tumor to the affected structures and systemic conditions such as diabetes mellitus. No treatment for radiation maculopathy or papillopathy has been proven to be effective in a randomized clinical trial.

Radiation injury to vital structures may be avoided or shielded with the use of materials such as lead that have a higher effective atomic number and density than tissue. However, solid metals are not amenable to use within the eye (Figure 1).

There have been previous efforts to try to use a vitreous substitute in order to protect intraocular structures from the deleterious effects of radiations. In an animal study, Finger et al, demonstrated that iodinated contrast agents (iophendylate, iohexol, and iopamidol) could block radiation intraocularly. But these substances were highly toxic and could not be retained in the eye due to high water solubility.

The technique of vitrectomy and oil tamponade during plaque brachytherapy has been performed previously in humans by Dr. Tara McCannel at UCLA. During a paper presentation at the 2010 meeting of the American Society of Retina Specialist in Vancouver, BC, the first series of 10 patients were presented, and no complications of the technique were reported. It is now a commonly applied technique at this center for treatment of choroidal melanoma (Oncology Times 2010; 32(14):36, UCLA, Clinical Update 2011; 20(1):1, 4)

In this prospective pilot study the investigators propose that patients will undergo standard plaque placement for treatment of their ocular melanoma in addition to pars plana vitrectomy and silicone oil infusion. When patients return for their scheduled plaque removal one week later, they will also undergo removal of the silicone oil from the eye. Placement of silicone oil should not alter the radiation dose delivered to the tumor, as there is no physical space between the tumor and the radioactive plaque for silicone oil to be present. The reduction in radiation to healthy ocular structures by using the oil technique may be sufficient to avoid the clinical complications caused by radiation-induced injury.

Eligibility criteria: Inclusion Criteria:

* All treatment-naïve patients with clinical diagnosis of primary choroidal melanoma, amenable to treatment with plaque brachytherapy, aged 18 or older regardless gender, race/ethnicity or existing medical condition unless they are specifically mentioned as exclusion criteria.
* Patients with best corrected visual acuity of 20/400 or better in the study eye.
* Patients in whom the calculated dose of radiation to the optic nerve or macula is \> 25 Gray (Gy).

Tumor inclusion criteria:

* Unilateral choroidal melanoma, medium size as defined by COMS classification:

  1. At least 2.5 mm in height, but no more than 10 mm in height (no more than 8.0 mm whenever the tumor was near the optic disc), and
  2. No more than 16.0 mm In diameter, regardless the shape by ultrasound.

Exclusion Criteria:

* History of previous treatment for the choroidal melanoma.
* Pregnancy.
* Patients with any impairment which prevent attending follow-up appointments.
* The presence of concomitant significant life-treating medical conditions that significantly reduces the life expectancy to less than three years.
* The presence of other vision-treating ophthalmic condition, not directly related with choroidal melanoma which is likely to going to require intraocular surgery in the next three years.
* Clinical or radiological evidence of the presence of metastatic disease.
* The presence of significant media opacity (e.g. cataract) that precludes the investigator's ability to grade the tumor, performs retina surgery, or performs follow-up assessments.
* Patients that do not accept the informed consent

Tumor exclusion criteria:

* Inability to successfully grade, stage and delineate the tumor by ultrasound.
* Tumor location that will prevent the correct placement of the plaque or have significant risk of optic nerve damage during plaque placement.
* Tumors that involved the anterior chamber angle, the iris or have detectable extrascleral extension.
* Tumor margin location \< 1000 µm from the fovea.

Primary outcomes:
measure: Vision Loss
timeFrame: 1 year
Secondary outcomes:
measure: Severe Visual Loss
timeFrame: 3 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Eye Center
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Scott C Oliver, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Raul Velez-Montoya, MD
role: PRINCIPAL_INVESTIGATOR
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