Stereotactic Body Radiation Therapy and Aflibercept in Treating Patients With Uveal Melanoma

• ClinicalTrials.gov Identifier: NCT03712904
• Recruitment Status: Completed
• First Posted: October 19, 2018
• Last Update Posted: January 6, 2023
• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Uveal Melanoma	Radiation: Stereotactic Body Radiation Therapy; Biological: Ziv-Aflibercept	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Randomized Trial of Stereotactic Radiotherapy (SRT) Followed by Intravitreal Aflibercept Injection for Patients With Ocular Melanoma
• Actual Study Start Date: August 9, 2019
• Actual Primary Completion Date: September 20, 2022
• Actual Study Completion Date: December 23, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Radiation: Stereotactic Body Radiation Therapy; Undergo radiation; Other Names: SBRT; Stereotactic Ablative Body Radiation Therapy
Experimental: 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.	Biological: Ziv-Aflibercept; Given IV; Other Names: 724770; 862111-32-8; AVE0005; Eylea; Vascular Endothelial Growth Factor Trap

Outcome Measures

Primary Outcome Measures :

1. Incidence of grade 3 or higher toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 2 years ]
   Will be determined by patients who experience grade >= 3 toxicity related to stereotactic radiation therapy and/or intravitreal aflibercept. Will be tested using one-sided exact binomial test with alpha 0.05. The two arms will be combined for the primary analysis

Secondary Outcome Measures :

1. Radiation maculopathy rate defined as ophthalmoscopic detection of macular edema perivascular sheathing [ Time Frame: At 2 years ]
   Will be estimated separately in each arm with the corresponding exact binomial 90% confidence interval.
2. Radiation papillopathy rate defined as ophthalmoscopic detection of peripapillary encircling nerve fiber layer infarction [ Time Frame: At 2 years ]
   Will be estimated separately in each arm with the corresponding exact binomial 90% confidence interval.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Pennsylvania

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

Sidney Kimmel Cancer Center at Thomas Jefferson University

Regeneron Pharmaceuticals

Investigators

• Principal Investigator: Wenyin Shi, MD, PhD; Sidney Kimmel Cancer Center at Thomas Jefferson University

More Information

Additional Information:

Sidney Kimmel Cancer Center at Thomas Jefferson University 

Thomas Jefferson University Hospital 

• Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT03712904
• Other Study ID Numbers: 18P.457
• First Posted: October 19, 2018
• Last Update Posted: January 6, 2023
• Last Verified: January 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Aflibercept; Endothelial Growth Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents