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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

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