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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05504291




Registration number
NCT05504291
Ethics application status
Date submitted
4/08/2022
Date registered
17/08/2022
Date last updated
17/05/2024

Titles & IDs
Public title
A Study to Give Treatment Inside the Eye to Treat Retinoblastoma
Scientific title
Intravitreal Melphalan for Intraocular Retinoblastoma
Secondary ID [1] 0 0
NCI-2022-06082
Secondary ID [2] 0 0
ARET2121
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bilateral Retinoblastoma 0 0
Childhood Intraocular Retinoblastoma 0 0
Group D Retinoblastoma 0 0
Stage I Retinoblastoma 0 0
Unilateral Retinoblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Head and neck
Eye 0 0 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Biospecimen Collection
Treatment: Drugs - Carboplatin
Treatment: Drugs - Etoposide
Treatment: Surgery - Examination Under Anesthesia
Treatment: Drugs - Melphalan
Treatment: Surgery - Ultrasound Biomicroscopy
Treatment: Drugs - Vincristine

Experimental: Treatment (CVE, melphalan) - See Detailed Description


Treatment: Surgery: Biospecimen Collection
Undergo correlative studies

Treatment: Drugs: Carboplatin
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Surgery: Examination Under Anesthesia
Undergo imaging of the eye during EUA

Treatment: Drugs: Melphalan
Given I-VITRE

Treatment: Surgery: Ultrasound Biomicroscopy
Undergo UBM during EUA

Treatment: Drugs: Vincristine
Given IV
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Feasibility success rate of intravitreal melphalan injection in combination with systemic chemotherapy
Timepoint [1] 0 0
Up to cycle 6 (1 cycle = 28 days)
Secondary outcome [1] 0 0
Percentage of patients with grade 3 or higher toxicities
Timepoint [1] 0 0
Up to 30 days after last dose of study treatment
Secondary outcome [2] 0 0
Event-free survival (EFS)
Timepoint [2] 0 0
Up to 5 years

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 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

- 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
Minimum age
No limit
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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 to the study eye(s),
including focal, local, or systemic chemotherapy 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 no reasonable expectation for any useful vision in the Group D eye as
determined by the treating physician

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
28
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05504291
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Rachana Shah
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05504291