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

Primary Purpose

Uveal Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Stereotactic Body Radiation Therapy
Ziv-Aflibercept
Sponsored by
Sidney Kimmel Cancer Center at Thomas Jefferson University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Uveal Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

  • Sidney Kimmel Cancer Center at Thomas Jefferson University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

A. Stereotactic body radiation therapy, ziv-aflibercept

B. Stereotactic body radiation therapy, ziv-aflibercept

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Incidence of grade 3 or higher toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
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

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.
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.

Full Information

First Posted
October 17, 2018
Last Updated
January 4, 2023
Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03712904
Brief Title
Stereotactic Body Radiation Therapy and Aflibercept in Treating Patients With Uveal Melanoma
Official Title
Phase II Randomized Trial of Stereotactic Radiotherapy (SRT) Followed by Intravitreal Aflibercept Injection for Patients With Ocular Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
August 9, 2019 (Actual)
Primary Completion Date
September 20, 2022 (Actual)
Study Completion Date
December 23, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uveal Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A. Stereotactic body radiation therapy, ziv-aflibercept
Arm Type
Experimental
Arm Description
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.
Arm Title
B. Stereotactic body radiation therapy, ziv-aflibercept
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiation Therapy
Other Intervention Name(s)
SBRT, Stereotactic Ablative Body Radiation Therapy
Intervention Description
Undergo radiation
Intervention Type
Biological
Intervention Name(s)
Ziv-Aflibercept
Other Intervention Name(s)
724770, 862111-32-8, AVE0005, Eylea, Vascular Endothelial Growth Factor Trap
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Incidence of grade 3 or higher toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Description
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
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Radiation maculopathy rate defined as ophthalmoscopic detection of macular edema perivascular sheathing
Description
Will be estimated separately in each arm with the corresponding exact binomial 90% confidence interval.
Time Frame
At 2 years
Title
Radiation papillopathy rate defined as ophthalmoscopic detection of peripapillary encircling nerve fiber layer infarction
Description
Will be estimated separately in each arm with the corresponding exact binomial 90% confidence interval.
Time Frame
At 2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenyin Shi, MD, PhD
Organizational Affiliation
Sidney Kimmel Cancer Center at Thomas Jefferson University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Cancer Center at Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States

12. IPD Sharing Statement

Links:
URL
http://hospitals.jefferson.edu/
Description
Thomas Jefferson University Hospital

Learn more about this trial

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

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