Trial Title:
A Study to Give Treatment Inside the Eye to Treat Retinoblastoma
NCT ID:
NCT05504291
Condition:
Bilateral Retinoblastoma
Childhood Intraocular Retinoblastoma
Group D Retinoblastoma
Stage I Retinoblastoma
Unilateral Retinoblastoma
Conditions: Official terms:
Retinoblastoma
Carboplatin
Etoposide
Vincristine
Etoposide phosphate
Melphalan
Mechlorethamine
Podophyllotoxin
Nitrogen Mustard Compounds
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo aqueous humor and tissue sample collection
Arm group label:
Treatment (CVE, melphalan)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Given IV
Arm group label:
Treatment (CVE, melphalan)
Other name:
Blastocarb
Other name:
Carboplat
Other name:
Carboplatin Hexal
Other name:
Carboplatino
Other name:
Carboplatinum
Other name:
Carbosin
Other name:
Carbosol
Other name:
Carbotec
Other name:
CBDCA
Other name:
Displata
Other name:
Ercar
Other name:
JM-8
Other name:
JM8
Other name:
Nealorin
Other name:
Novoplatinum
Other name:
Paraplatin
Other name:
Paraplatin AQ
Other name:
Paraplatine
Other name:
Platinwas
Other name:
Ribocarbo
Intervention type:
Drug
Intervention name:
Etoposide
Description:
Given IV
Arm group label:
Treatment (CVE, melphalan)
Other name:
Demethyl Epipodophyllotoxin Ethylidine Glucoside
Other name:
EPEG
Other name:
Lastet
Other name:
Toposar
Other name:
Vepesid
Other name:
VP 16
Other name:
VP 16-213
Other name:
VP 16213
Other name:
VP-16
Other name:
VP-16-213
Other name:
VP-16213
Other name:
VP16
Other name:
VP16213
Intervention type:
Procedure
Intervention name:
Examination Under Anesthesia
Description:
Undergo imaging of the eye during EUA
Arm group label:
Treatment (CVE, melphalan)
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (CVE, melphalan)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
Melphalan
Description:
Given I-VITRE
Arm group label:
Treatment (CVE, melphalan)
Other name:
Alanine Nitrogen Mustard
Other name:
CB-3025
Other name:
L-PAM
Other name:
L-Phenylalanine Mustard
Other name:
L-Sarcolysin
Other name:
L-Sarcolysin Phenylalanine mustard
Other name:
L-Sarcolysine
Other name:
Melphalan for Injection-Hepatic Delivery System
Other name:
Melphalanum
Other name:
Phenylalanine Mustard
Other name:
Phenylalanine Nitrogen Mustard
Other name:
Sarcoclorin
Other name:
Sarkolysin
Other name:
WR-19813
Intervention type:
Procedure
Intervention name:
Ultrasound Biomicroscopy
Description:
Undergo UBM during EUA
Arm group label:
Treatment (CVE, melphalan)
Other name:
Ultrasound Biomicroscopy (UBM)
Intervention type:
Drug
Intervention name:
Vincristine
Description:
Given IV
Arm group label:
Treatment (CVE, melphalan)
Other name:
LCR
Other name:
Leurocristine
Other name:
VCR
Other name:
Vincrystine
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.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the feasibility of administering intravitreal melphalan by cycle 6 when
given in combination with systemic carboplatin, vincristine, and etoposide (CVE) for the
treatment of Group D retinoblastoma with vitreous seeding.
SECONDARY OBJECTIVES:
I. To determine the safety and toxicity profile associated with intravitreal melphalan in
combination with systemic CVE for the treatment of Group D retinoblastoma with vitreous
seeding.
II. To evaluate the efficacy of intravitreal melphalan in conjunction with systemic
chemotherapy in Group D intraocular retinoblastoma with vitreous seeding.
EXPLORATORY OBJECTIVES:
I. To determine if eyes that become eligible for injection at cycle 3 or later would have
been eligible for injection at diagnosis by retrospective central review of examination
under anesthesia (EUA) and ultrasound biomicroscopy (UBM) images from diagnosis.
II. To validate and standardize the extraction, storage and collection protocols across
multiple centers to demonstrate that aqueous humor from eyes undergoing therapy have high
enough tumor-derived deoxyribonucleic acid (DNA) concentration for whole genome
sequencing and RB1 testing.
III. To explore the relationship between highly-recurrent retinoblastoma (RB) somatic
copy number alterations (SCNAs) and ocular salvage as well as tumor fraction (% of tumor
DNA) as a marker of minimal residual disease and risk of intraocular disease relapse.
IV. To evaluate the effects of intravitreal melphalan therapy in the histopathology of
enucleated eyes for progressive or recalcitrant retinoblastoma while on therapy.
V. To evaluate the long-term visual potential of eyes salvaged using intravitreal
therapy.
OUTLINE:
CYCLES 1-2: Patients receive CVE regimen consisting of: carboplatin intravenously (IV)
over 15-60 minutes on days 1 and 2 of each cycle, vincristine IV on day 1 of each cycle,
and etoposide IV over 90-120 minutes on day 1 and 2 of each cycle. Treatment repeats
every 28 days for up to 2 cycles in the absence of disease progression or unacceptable
toxicity. Patients also undergo ultrasound biomicroscopy (UBM) and imaging of the eye
during a procedure called examination under anesthesia (EUA) at baseline and prior to
each cycle. NOTE: UBM is completed prior to cycle 1 only.
CYCLES 3+: Patients receive CVE regimen as in cycles 1-2. Patients also undergo EUA prior
to each cycle to determine eligibility to receive melphalan. If found eligible, patients
receive intravitreal injection of melphalan once between days -14 to 14 of each cycle.
Patients who are not eligible for melphalan for any cycle receive CVE only regimen for
that cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease
progression or unacceptable toxicity. NOTE: Patients may be eligible to receive
additional cycles of melphalan alone (maximum of 6 injections).
Additionally, patients undergo magnetic resonance imaging and may undergo aqueous humor
and tissue sample collection throughout the trial.
After completion of study treatment, patients are followed up at 4 weeks, then every 3
months for 1 year, and then every 3-6 months for years 2-5.
Criteria for eligibility:
Criteria:
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
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
Gender:
All
Minimum age:
N/A
Maximum age:
18 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Children's Hospital of Alabama
Address:
City:
Birmingham
Zip:
35233
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
205-638-9285
Email:
oncologyresearch@peds.uab.edu
Investigator:
Last name:
Elizabeth D. Alva
Email:
Principal Investigator
Facility:
Name:
Children's Hospital Los Angeles
Address:
City:
Los Angeles
Zip:
90027
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
323-361-4110
Investigator:
Last name:
Rachana Shah
Email:
Principal Investigator
Facility:
Name:
Lucile Packard Children's Hospital Stanford University
Address:
City:
Palo Alto
Zip:
94304
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-694-0012
Email:
ccto-office@stanford.edu
Investigator:
Last name:
Jay Michael S. Balagtas
Email:
Principal Investigator
Facility:
Name:
Children's Hospital Colorado
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
303-764-5056
Email:
josh.b.gordon@nsmtp.kp.org
Investigator:
Last name:
Sandra Luna-Fineman
Email:
Principal Investigator
Facility:
Name:
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Address:
City:
Atlanta
Zip:
30329
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
404-785-2025
Email:
Leann.Schilling@choa.org
Investigator:
Last name:
Thomas A. Olson
Email:
Principal Investigator
Facility:
Name:
C S Mott Children's Hospital
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-865-1125
Investigator:
Last name:
Laura Sedig
Email:
Principal Investigator
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Daniel Willis
Email:
Principal Investigator
Facility:
Name:
Duke University Medical Center
Address:
City:
Durham
Zip:
27710
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
888-275-3853
Investigator:
Last name:
Jessica M. Sun
Email:
Principal Investigator
Facility:
Name:
Children's Hospital Medical Center of Akron
Address:
City:
Akron
Zip:
44308
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
330-543-3193
Investigator:
Last name:
Erin Wright
Email:
Principal Investigator
Facility:
Name:
Cleveland Clinic Foundation
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
866-223-8100
Email:
TaussigResearch@ccf.org
Investigator:
Last name:
Matteo M. Trucco
Email:
Principal Investigator
Facility:
Name:
Saint Jude Children's Research Hospital
Address:
City:
Memphis
Zip:
38105
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
888-226-4343
Email:
referralinfo@stjude.org
Investigator:
Last name:
Carlos Rodriguez-Galindo
Email:
Principal Investigator
Facility:
Name:
Dell Children's Medical Center of Central Texas
Address:
City:
Austin
Zip:
78723
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
512-628-1902
Email:
TXAUS-DL-SFCHemonc.research@ascension.org
Investigator:
Last name:
Shannon M. Cohn
Email:
Principal Investigator
Facility:
Name:
UT Southwestern/Simmons Cancer Center-Dallas
Address:
City:
Dallas
Zip:
75390
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
214-648-7097
Email:
canceranswerline@UTSouthwestern.edu
Investigator:
Last name:
Daniel C. Bowers
Email:
Principal Investigator
Facility:
Name:
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
713-798-1354
Email:
burton@bcm.edu
Investigator:
Last name:
Murali M. Chintagumpala
Email:
Principal Investigator
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-632-6789
Email:
askmdanderson@mdanderson.org
Investigator:
Last name:
Najat C. Daw
Email:
Principal Investigator
Facility:
Name:
Primary Children's Hospital
Address:
City:
Salt Lake City
Zip:
84113
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
801-585-5270
Investigator:
Last name:
Matthew Dietz
Email:
Principal Investigator
Facility:
Name:
Children's Hospital of Wisconsin
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
414-955-4727
Email:
MACCCTO@mcw.edu
Investigator:
Last name:
Kerri Becktell
Email:
Principal Investigator
Facility:
Name:
Perth Children's Hospital
Address:
City:
Perth
Zip:
6009
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Email:
helpdesk@childrensoncologygroup.org
Investigator:
Last name:
Marianne B. Phillips
Email:
Principal Investigator
Facility:
Name:
Centre Hospitalier Universitaire Sainte-Justine
Address:
City:
Montreal
Zip:
H3T 1C5
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
514-345-4931
Email:
yvan.samson@umontreal.ca
Investigator:
Last name:
Monia Marzouki
Email:
Principal Investigator
Start date:
November 4, 2022
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Children's Oncology Group
Agency class:
Other
Source:
Children's Oncology Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05504291