Genetic Research for Inherited Eye Diseases

Overseen By Naris Nilubol, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Chemotherapy, Immunotherapy, Investigational therapies

Disqualifiers: Prior radiation, Infection, Uncontrolled diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new radiation therapy approach for individuals with adrenocortical carcinoma (ACC), a rare cancer of the adrenal glands, to determine if it prevents cancer recurrence after surgery. The treatment uses preoperative external beam radiation therapy (EBRT) before surgically removing the tumors. Participants should have ACC that has returned after previous treatments but can still be safely removed with surgery. The study seeks individuals suitable for both radiation therapy and surgery. Participants will undergo radiation treatment for about 2-3 weeks, followed by surgery approximately 4 weeks later, with follow-ups for 10 years. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants may continue mitotane if they have used it before, at the discretion of the treating investigator. It's best to discuss your specific medications with the trial team.

What prior data suggests that this external beam radiation therapy is safe for treating ACC?

Research has shown that radiation therapy before surgery can sometimes cause serious side effects, especially around the eyes. However, using different types of radiation, such as proton beam therapy, might reduce the risk of problems like cataracts and other eye issues.

Studies on surgery for tumors indicate that it is generally safe. Most patients retain their vision, and only a few experience major issues like bleeding or retinal detachment.

Since this trial is in its early phase, researchers are primarily focused on assessing safety. Early-phase trials usually involve small groups of people to closely monitor any side effects. Although there is limited safety data, the information collected will help understand how well people tolerate the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for inherited eye diseases, which often focus on managing symptoms or slowing progression, this new approach combines preoperative radiation therapy (RT) with surgical resection. Researchers are excited because the escalating doses of preoperative RT aim to shrink abnormal tissue before surgery, potentially making the surgical procedure more effective and less invasive. This combination could offer a more targeted attack on the underlying genetic issues, providing hope for improved outcomes and vision preservation.

What evidence suggests that preoperative external beam radiation therapy might be an effective treatment for adrenocortical carcinoma?

Research shows that external beam radiation therapy (EBRT), a treatment in this trial, effectively treats tumors. Studies have found that EBRT can save about 46% of eyes in certain cases, demonstrating its ability to shrink tumors or halt their growth. Surgical resection, another treatment option in this trial, involves removing tumors through surgery and often serves as a strong option for many cancers. It has successfully preserved or improved function in other tumor types. In this trial, using EBRT before surgery aims to reduce tumor size, facilitating easier and more successful surgical removal. Although data on adrenocortical carcinoma (ACC) is limited, this approach draws on promising results from other cancers. ^{2 6 7 8 9}

Who Is on the Research Team?

Naris Nilubol, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

The eyeGENE(R) Stage 3 trial is for people of any age with certain inherited eye diseases, such as aniridia, Best disease, blue-cone monochromacy, corneal dystrophy, and pigmentation disorders like albinism. Unaffected relatives may also participate.

Inclusion Criteria

Breastfeeding participants must discontinue breastfeeding until 4 months following cytoreductive surgery

Ability to understand and willingness to sign a written informed consent document

I agree to have a biopsy of my tumor before starting the study treatment.

Exclusion Criteria

I have had another type of cancer in the past 3 years.

I have an adrenal tumor that hasn't been fully diagnosed.

I have had radiation therapy to my abdomen before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Preoperative Radiation Therapy

Participants receive external beam radiation therapy (EBRT) 5 days a week for 2 to 3 weeks

2-3 weeks

5 visits per week (in-person)

Surgery

Participants undergo surgical resection of tumors 4 to 8 weeks after completing EBRT

1-3 weeks (hospital stay)

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits for 10 years

10 years

Every 3 months for 3 years, then every 6 months for 7 years (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Preoperative external beam radiation therapy (EBRT)
• Surgical resection

Trial Overview This study aims to expand a DNA and data repository by collecting saliva or blood samples from participants with rare eye diseases. The collected information will help establish links between genetics and symptoms of these conditions.

How Is the Trial Designed?

Group I: Preop RT + surgery Experimental Treatment 2 Interventions

Preoperative RT at escalating doses followed by surgical resection

Surgical resection is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Surgical resection for:

• Sinonasal melanoma
• Cancerous tumors
• Benign tumors

Approved in United States as Surgical resection for:

• Sinonasal melanoma
• Cancerous tumors
• Benign tumors
• Mediastinal masses
• Esophageal cancers

Approved in Canada as Surgical resection for:

• Sinonasal melanoma
• Cancerous tumors
• Benign tumors

Approved in Japan as Surgical resection for:

• Sinonasal melanoma
• Cancerous tumors
• Benign tumors

Approved in China as Surgical resection for:

• Sinonasal melanoma
• Cancerous tumors
• Benign tumors

Approved in Switzerland as Surgical resection for:

• Sinonasal melanoma
• Cancerous tumors
• Benign tumors

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7989770/

Clinical Spectrum and Outcomes of Ocular and Periocular ... High-dose EBRT for inoperable MMST can lead to a wide array of severe ocular/periocular complications. AMT serves as a potentially useful treatment modality.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7852425/

Prognostic Factors for Eye Globe Salvage by External Beam ... Radiation is associated with a 36%–51% risk of second cancers in heritable retinoblastoma that increases with patient's age, which is more than three times the ...

3. researchgate.net researchgate.net/publication/339365092_The_role_of_external_beam_radiation_therapy_for_retinoblastoma_after_failure_of_combined_chemoreduction_and_focal_consolidation_therapy

(PDF) The role of external beam radiation therapy for ... Results indicated that external beam radiation therapy was able to save 46% of the eyes with a follow-up of 75 months. 84 These results suggest ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/aos.13729

Cosmetic results of enucleation and/or external beam ... External beam radiation therapy (EBRT) resulted in orbital and mid-facial growth retardation (Imhof et al. 1996) and increased the risk of ...

5. jamanetwork.com jamanetwork.com/journals/jamaophthalmology/fullarticle/416124

External Beam Radiation Salvage Therapy in Transgenic ... ObjectiveTo determine the efficacy of low-dose 'salvage' external beam radiationtherapy (EBRT) following failed subconjunctival carboplatin chemotherapy.

6. careacross.com careacross.com/clinical-trials/trial/NCT06487481

National Ophthalmic Genotyping and Phenotyping Network ... Description: Preoperative external beam radiation therapy (EBRT) at escalating doses daily 5 days/week (M-F) for 2-3 weeks; 2 weeks (DL1), or 3 weeks (DL2 or ...

7. mdpi.com mdpi.com/2072-6694/13/8/1862

Feasibility of Proton Beam Therapy as a Rescue ... This possibly reduces not only ocular side effects such as cataract development, orbital fat atrophy, and the incidence of bone growth abnormalities, but ...

8. researchgate.net researchgate.net/publication/24241929_Salvage_external_beam_radiotherapy_after_failed_primary_chemotherapy_for_bilateral_retinoblastoma_Rate_of_eye_and_vision_preservation

Salvage external beam radiotherapy after failed primary ... This is a retrospective observational case series. The outcome measures after EBRT are: rate of eye preservation, rate of tumour control, visual ...

9. nei.nih.gov nei.nih.gov/about/news-and-events/news/scientists-find-similar-survival-rates-eye-cancer-therapies

Scientists Find Similar Survival Rates for Eye Cancer Therapies Researchers reported that patients had similar survival rates regardless of whether their eyes were treated with external beam radiation prior to removal of the ...