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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT05504291
Registration number
NCT05504291
Ethics application status
Date submitted
4/08/2022
Date registered
17/08/2022
Date last updated
21/08/2024
Titles & IDs
Public title
A Study to Give Treatment Inside the Eye to Treat Retinoblastoma
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Scientific title
Intravitreal Melphalan for Intraocular Retinoblastoma
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Secondary ID [1]
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NCI-2022-06082
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Secondary ID [2]
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ARET2121
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Bilateral Retinoblastoma
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Childhood Intraocular Retinoblastoma
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Group D Retinoblastoma
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Stage I Retinoblastoma
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Unilateral Retinoblastoma
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Condition category
Condition code
Cancer
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Children's - Other
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Cancer
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Head and neck
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Eye
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Diseases / disorders of the eye
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Surgery - Biospecimen Collection
Treatment: Drugs - Carboplatin
Treatment: Drugs - Etoposide
Treatment: Surgery - Examination Under Anesthesia
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Drugs - Melphalan
Treatment: Surgery - Ultrasound Biomicroscopy
Treatment: Drugs - Vincristine
Experimental: Treatment (CVE, melphalan) - See Detailed Description
Treatment: Surgery: Biospecimen Collection
Undergo aqueous humor and tissue sample collection
Treatment: Drugs: Carboplatin
Given IV
Treatment: Drugs: Etoposide
Given IV
Treatment: Surgery: Examination Under Anesthesia
Undergo imaging of the eye during EUA
Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI
Treatment: Drugs: Melphalan
Given I-VITRE
Treatment: Surgery: Ultrasound Biomicroscopy
Undergo UBM during EUA
Treatment: Drugs: Vincristine
Given IV
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Intervention code [1]
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Treatment: Surgery
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Intervention code [2]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Feasibility success rate of intravitreal melphalan injection in combination with systemic chemotherapy
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Assessment method [1]
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A patient will be considered to have experienced intravitreal injection feasibility success if intravitreal melphalan can be delivered by cycle 6. If the treating physician does not inject because the eye has a full complete response (CR) for vitreous seeds after 2 cycles of systemic chemotherapy, it will be counted as a success in the feasibility analysis. Any feasibility evaluable patient who does not experience feasibility success will be considered a feasibility failure. For a bilateral patient with two Group D eyes with vitreous seeds, he/she will be categorized based on the worse results with the intent of being conservative, i.e., if intravitreal melphalan can be delivered in one eye but not the other by cycle 6 for any reason other than a CR of vitreal seeds, the patient will be deemed as experiencing a failure.
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Timepoint [1]
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Up to cycle 6 (1 cycle = 28 days)
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Secondary outcome [1]
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Percentage of patients with grade 3 or higher toxicities
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Assessment method [1]
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Any eligible patient who receives protocol therapy will be considered as evaluable for toxicity.
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Timepoint [1]
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Up to 30 days after last dose of study treatment
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Secondary outcome [2]
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Event-free survival (EFS)
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Assessment method [2]
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Any eligible patient who receives protocol therapy will be considered as evaluable for EFS. Patients who need non-protocol chemotherapy for either the study eye or non-study eye, external beam radiotherapy for either the study eye or non-study eye, or enucleation for the study eye will be considered as having a treatment failure and be considered as experiencing EFS events. The analysis will be conducted per patient level. The EFS along with the 95% confidence intervals will be estimated using the Kaplan-Meier method.
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Timepoint [2]
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Up to 5 years
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Eligibility
Key inclusion criteria
* Patient must be < 18 years of age at enrollment
* Patient must have newly diagnosed intraocular (localized) retinoblastoma and meet one of the following criteria:
* Unilateral Group D retinoblastoma with vitreous seeding; OR
* Bilateral retinoblastoma with worst eye Group D, with vitreous seeding present and the contralateral eye is Group A-C; OR
* Bilateral Group D retinoblastoma with at least one eye with vitreous seeding; OR
* Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has been enucleated prior to any therapy. Note exclusion for high-risk features
* Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has not been enucleated prior to any therapy at the discretion of the treating physician. Note exclusion for patients with evidence of metastatic or extra orbital spread
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =<16 years of age
* Peripheral absolute neutrophil count (ANC) >= 750/uL (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Platelet count >= 75,000/uL (transfusion independent) (must be performed within 7 days prior to enrollment)
* A serum creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment):
* 1 month to < 6 months = 0.4 (male and female)
* 6 months to < 1 year = 0.5 (male and female)
* 1 to < 2 years = 0.6 (male and female)
* 2 to < 6 years = 0.8 (male and female)
* 6 to < 10 years = 1.0 (male and female)
* 10 to < 13 years = 1.2 (male and female)
* 13 to < 16 years = 1.5 (male) and 1.4 (female)
* >= 16 years = 1.7 (male) and 1.4 (female) OR - a 24-hour urine Creatinine clearance >= 70 mL/min/1.73 m^2 OR - a glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* For patients < 1 month of age, serum creatinine levels must be < 1.5 x the treating institution's creatinine upper limit of normal (ULN) for patients < 1 month of age or the creatinine clearance or radioisotope GFR must be >= 70 mL/min/1.73 m^2
* Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
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Minimum age
No limit
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Maximum age
18
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Patients with evidence of metastatic or extra-orbital spread
* Patients must not have an invasive infection at time of protocol entry
* Patients must not have had any prior anti-cancer therapy other than cryotherapy and/or laser therapy (green or infrared) to the study eye(s) and non-study eye, including systemic chemotherapy, intra-arterial chemotherapy, radioactive plaque, brachytherapy, or radiation therapy.
* Note: A study eye is defined as being Group D with vitreous seeding. Patients may have had enucleation of one eye as long as the remaining eye is Group D with vitreous seeds
* Patients with bilateral disease who undergo enucleation of a Group E eye prior to initiation of therapy and show evidence of high-risk histopathology features in the enucleated eye. High-risk histopathology includes choroid involvement >= 3 mm, post lamina optic nerve involvement, full thickness scleral invasion or optic nerve invasion to the cut end
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
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Study design
Purpose of the study
Treatment
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Allocation to intervention
NA
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
4/11/2022
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
31/12/2026
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Actual
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Sample size
Target
26
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
WA
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Recruitment hospital [1]
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Perth Children's Hospital - Perth
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Recruitment postcode(s) [1]
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6009 - Perth
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Recruitment outside Australia
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United States of America
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State/province [1]
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Alabama
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United States of America
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State/province [2]
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California
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Country [3]
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United States of America
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State/province [3]
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Colorado
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United States of America
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State/province [4]
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Michigan
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Country [5]
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United States of America
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Missouri
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United States of America
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North Carolina
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Country [7]
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United States of America
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Ohio
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Country [8]
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United States of America
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Tennessee
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Country [9]
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United States of America
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State/province [9]
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Texas
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United States of America
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State/province [10]
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Utah
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Country [11]
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Canada
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State/province [11]
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Quebec
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Funding & Sponsors
Primary sponsor type
Other
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Name
Children's Oncology Group
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This phase II trial tests the safety and side effects of adding melphalan (by injecting it into the eye) to standard chemotherapy in early treatment of patients with retinoblastoma (RB). RB is a type of cancer that forms in the tissues of the retina (the light-sensitive layers of nerve tissue at the back of the eye). It may be hereditary or nonhereditary (sporadic). RB is considered harder to treat (higher risk) when there are vitreous seeds present. Vitreous seeds are RB tumors in the jelly-like fluid of the eye (called the vitreous humor). The term, risk, refers to the chance of the cancer not responding to treatment or coming back after treatment. Melphalan is in a class of medications called alkylating agents. It may kill cancer cells by damaging their deoxyribonucleic acid (DNA) and stopping them from dividing. Other chemotherapy drugs given during this trial include carboplatin, vincristine, and etoposide. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Adding melphalan to standard chemotherapy early in treatment may improve the ability to treat vitreous seeds and may be better than standard chemotherapy alone in treating retinoblastoma.
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Trial website
https://clinicaltrials.gov/study/NCT05504291
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Rachana Shah
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Address
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Children's Oncology Group
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Fax
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Email
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Contact person for public queries
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Address
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Fax
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Email
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT05504291
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