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Anesthetics

Radiation given daily for 5 days in a row each week (except for Saturdays, Sundays, and holidays). The whole treatment will take about 4-6 weeks. Ophthalmic examination under anesthesia including dilated eye exam, ocular fundus photography (Ret-Cam), ocular echography and neuro-radiologic assessment (as deemed necessary)

Radiation given daily for 5 days in a row each week (except for Saturdays, Sundays, and holidays). The whole treatment will take about 4-6 weeks.

Proton Beam Radiation Therapy

Ophthalmic examination under anesthesia including dilated eye exam, ocular fundus photography (Ret-Cam), ocular echography and neuro-radiologic assessment (as deemed necessary)

Ophthalmic EUA

Dan Gombos, MD

The purpose of this trial is to evaluate proton beam radiation therapy as an alternative to external photon beam irradiation in children with retinoblastoma as a means of local tumor control and ocular retention.

External photon beam radiation therapy (which is current standard of care) has been used in the treatment of retinoblastoma. It is a form of radiation therapy in which the radiation is delivered by a machine pointed at the area to be radiated.

Proton beam radiation therapy is a form of external photon beam radiation therapy, but it may be more effective because its adjusted dosing delivers less radiation to surrounding areas of the tumor, which helps preserve other tissues and cause fewer side effects.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. Your eye doctor will perform an assessment of your eye, including an exam while you are under anesthesia. This exam will include a dilated eye exam, photography of your affected eye (by a Ret-Cam), ultrasound of your affected eye, and imaging scans, such as computed tomography (CT) or magnetic resonance imaging (MRI), if the doctor thinks it is necessary. The assessments will be done to check and confirm the status of the disease.

After diagnosis of retinoblastoma, the study doctor will first see if external photon beam radiation therapy is a reasonable treatment option for you. If external photon beam radiotherapy is deemed appropriate for you, you will be eligible to receive proton beam radiation therapy in this study.

If you are found to be eligible to take part in this study, you will be treated with proton beam radiation therapy. Treatment will begin within 1 week of referral to the M. D. Anderson Proton Center. It will be given daily for 5 days in a row each week (except for Saturdays, Sundays, and holidays). The whole treatment will take about 4-6 weeks.

Within 2-4 weeks after completion of therapy, you will have an eye exam performed under anesthesia (like the one during screening). You will have repeated eye exams under anesthesia, depending on the appearance and response of the tumor to therapy. This will occur about every 1-4 months.

You will continue to have these eye exams until the tumors are considered to be stable or unless your disease gets worse.

If the disease gets worse or you experience any intolerable side effects, you may be taken off treatment.

You will be required to have lifelong eye and medical assessments to continue to monitor you for disease. If no disease is found 5 years after completion of proton beam radiation therapy, you will be considered free of disease. You will then have annual (yearly) eye and pediatric assessment through adulthood.

This is an investigational study. Up to 20 patients will take part in this study. All will be enrolled at M.D. Anderson.

Proton Beam Radiation Therapy for Intraocular and Periocular Retinoblastoma

A Phase II Trial of Proton Beam Radiation Therapy for Intra- and Periocular Retinoblastoma

Where proton beam radiation therapy used as an alternative to external photon beam irradiation in children with retinoblastoma as a means of local tumor control and ocular retention, local tumor control measured for participants with a globe as tumor regression with ocular retention, and for post enucleation measured as lack of orbital tumor recurrence.

M.D. Anderson Cancer Center

Proton Beam Radiation Therapy given daily for 5 days in a row each week where whole treatment takes about 4-6 weeks. Ophthalmic examination under anesthesia including dilated eye exam, ocular fundus photography (Ret-Cam), ocular echography and neuro-radiologic assessment (as deemed necessary).

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

No analysis performed as a result of small study population.

Dan Gombos, MD/Professor, Ophthalmology

No analysis performed. Study did not meet anticipated enrollment.

Rate of Local Control in the Globe at 12 Months

Overall Study

Antineoplastic Agents

Dermatologic Agents

Amino Acids

Etoposide

Carboplatin

Vincristine

Melphalan

Etoposide phosphate

Podophyllotoxin

Mechlorethamine

Nitrogen Mustard Compounds

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Keratolytic Agents

Phenylalanine

Alanine

Biospecimen Collection

Examination Under Anesthesia

Ultrasound Biomicroscopy

Site Public Contact

Elizabeth D. Alva

Jay Michael S. Balagtas

Sandra Luna-Fineman

Laura Sedig

Daniel Willis

Jessica M. Sun

Erin Wright

Rabi Hanna

Carlos Rodriguez-Galindo

Shannon M. Cohn

Daniel C. Bowers

Murali M. Chintagumpala

Najat C. Daw

Marianne B. Phillips

Rachana Shah

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.

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).

After completion of study treatment, patients are followed up periodically until 5 years from study enrollment.

A Study to Give Treatment Inside the Eye to Treat Retinoblastoma

Intravitreal Melphalan for Intraocular Retinoblastoma

In order to determine if eyes that become eligible for injection at cycle 3 or later would have been eligible for injection at diagnosis, the retrospective central review on images from diagnosis for eyes that are eligible for injection at cycle 3 or later will be summarized.

Extract tumor-derived deoxyribonucleic acid (DNA), from aqueous humor, for whole genome sequencing and retinoblastoma (RB)1 testing.

Will explore the relationship between highly-recurrent RB SCNAs and tumor fraction (% of tumor DNA) as a marker of minimal residual disease and risk of intraocular disease relapse.

Will explore the relationship between highly-recurrent RB 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.

Will be calculated along with the 95% confidence interval. The number of evaluable eyes for this aim will depend on the ocular salvage rate.

Eligible patients who retain the affected eye will be evaluated for visual acuity. The visual acuity will be evaluated prior to cycle 1 and at one year from end of therapy, if age-appropriate. The visual acuity data will be summarized by evaluation time points.

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.

Any eligible patient who receives protocol therapy will be considered as evaluable for toxicity.

Any eligible patient who receives protocol therapy will be considered as evaluable for EFS. Patients who need non-protocol chemotherapy, external beam radiotherapy, or enucleation 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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Proton Beam Radiation Therapy for Intraocular and Periocular Retinoblastoma	NCT00432445	Retinoblastoma	Proton Beam Rad... Ophthalmic EUA	-	M.D. Anderson Cancer Center
A Study to Give Treatment Inside the Eye to Treat Retinoblastoma	NCT05504291	Bilateral Retin... Childhood Intra... Group D Retinob... Stage I Retinob... Unilateral Reti...	Biospecimen Col... Carboplatin Etoposide Examination Und... Melphalan Ultrasound Biom... Vincristine	- 18 Years	Children's Oncology Group

Spots Global Cancer Trial Database for examination under anesthesia