Uveal Melanoma
Conditions
Brief summary
This phase II trial studies how well stereotactic body radiation therapy and aflibercept work in treating patients with uveal melanoma. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Aflibercept may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving stereotactic body radiation therapy followed by aflibercept may work better in treating patients with uveal melanoma.
Detailed description
PRIMARY OBJECTIVES: I. To assess the percentage of patients able to successfully complete their prescribed treatment of radiation and intravitreal ziv-aflibercept (aflibercept) injection (IAI) with an acceptable level of toxicity. SECONDARY OBJECTIVES: I. To assess for reduction in the incidence of 2-year rates of radiation maculopathy, radiation papillopathy, functional vision preservation, radiation glaucoma, and to assess 2-year local control and progression-free survival.
Interventions
RADIATIONStereotactic Body Radiation Therapy
Undergo radiation
BIOLOGICALZiv-Aflibercept
Given IV
Sponsors
Regeneron Pharmaceuticals
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Provide signed and dated informed consent form or have a Legally Authorized Representative (LAR) who can give consent * Willing to comply with all study procedures and be available for the duration of the study * Must be a candidate for radiation therapy * Karnofsky performance status (KPS) \>= 60 * Diagnosed with uveal melanoma either clinically or pathologically on biopsy * Uveal melanoma of one eye only * Localized uveal melanoma, with no evidence of metastasis * Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days prior to enrollment
Exclusion criteria
* Tumor thickness more than 14 mm as measured by ultrasound * Active collagen vascular disease * Any contraindication to intravitreal injections including: elevated intraocular pressure, ocular or periocular infection, active intraocular inflammation, or other determined by treating physician * Known allergic reactions to components of intravitreal Aflibercept * Patients with known hypercoagulable syndromes * Prior radiation to the eye or brain * Life expectancy less than 6 months * Blind in both eyes * Patients unable to receive contrast enhanced brain magnetic resonance imaging (MRI) * Deaf in both ears * Patients have hypersensitivity to intravitreal Aflibercept * Patients is on or within 1 month of systemic anti-VEGF treatment * Patients who are candidates for brachytherapy * Patients for whom enucleation is standard of care * Pregnancy or active breastfeeding. Sexually active men or women of childbearing potential who are unwilling to practice adequate contraception prior to the initial dose/start of the first treatment, during the study, and for at least 3 months after the last dose. Adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly * Contraception is not required for men with documented vasectomy * Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | Up to approximately 6 months | Percent of patients who experience Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade ≥3 toxicity related to SRT and/or intravitreal Aflibercept. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiation Maculopathy Rate Defined as Ophthalmoscopic Detection of Macular Edema Perivascular Sheathing | At 2 years | Will be estimated separately in each arm with the corresponding exact binomial 90% confidence interval. |
| Radiation Papillopathy Rate Defined as Ophthalmoscopic Detection of Peripapillary Encircling Nerve Fiber Layer Infarction | At 2 years | Will be estimated separately in each arm with the corresponding exact binomial 90% confidence interval. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A. Stereotactic Body Radiation Therapy, Ziv-aflibercept Patients undergo stereotactic body radiation therapy over 5 fractions every other week day during days 1-10. Patients then receive ziv-aflibercept IVI on the last day of radiation therapy and then every 2 months for up to 2 years in the absence of disease progression or unacceptable toxicity.
Stereotactic Body Radiation Therapy: Undergo radiation | 1 |
| B. Stereotactic Body Radiation Therapy, Ziv-aflibercept Patients undergo stereotactic body radiation therapy as in arm A. Patients then receive ziv-aflibercept IVI on the last day of radiation therapy and then every 4 months for up to 2 years in the absence of disease progression or unacceptable toxicity.
Ziv-Aflibercept: Given IV | 2 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | progression/eye removed before 2 years (unable to complete testing) | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | A. Stereotactic Body Radiation Therapy, Ziv-aflibercept | B. Stereotactic Body Radiation Therapy, Ziv-aflibercept | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 1 participants | 2 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 1 / 2 |
| other Total, other adverse events | 1 / 1 | 2 / 2 |
| serious Total, serious adverse events | 0 / 1 | 1 / 2 |
Outcome results
Primary
Incidence of Adverse Events
Percent of patients who experience Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade ≥3 toxicity related to SRT and/or intravitreal Aflibercept.
Time frame: Up to approximately 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A. Stereotactic Body Radiation Therapy, Ziv-aflibercept | Incidence of Adverse Events | 0 Participants |
| B. Stereotactic Body Radiation Therapy, Ziv-aflibercept | Incidence of Adverse Events | 0 Participants |
Secondary
Radiation Maculopathy Rate Defined as Ophthalmoscopic Detection of Macular Edema Perivascular Sheathing
Will be estimated separately in each arm with the corresponding exact binomial 90% confidence interval.
Time frame: At 2 years
Population: No participants were evaluable for this outcome. One participant withdrew consent, one experienced disease progression requiring eye removal prior to the assessment time point, and one died before reaching the two year mark. Subject who died was no longer a patient at the institution and their death was found through obituary search.
Secondary
Radiation Papillopathy Rate Defined as Ophthalmoscopic Detection of Peripapillary Encircling Nerve Fiber Layer Infarction
Will be estimated separately in each arm with the corresponding exact binomial 90% confidence interval.
Time frame: At 2 years
Population: No participants were evaluable for this outcome. One participant withdrew consent, one experienced disease progression requiring eye removal prior to the assessment time point, and one died before reaching the two year mark. Subject who died was no longer a patient at the institution and their death was found through obituary search.