National Ophthalmic Genotyping and Phenotyping Network (eyeGENE(R)), Stage 3-Expansion of DNA and Data Repositories for Rare Inherited Ophthalmic Diseases

Trial Title: National Ophthalmic Genotyping and Phenotyping Network (eyeGENE(R)), Stage 3-Expansion of DNA and Data Repositories for Rare Inherited Ophthalmic Diseases

NCT ID: NCT06487481

Condition: Adrenocortical Carcinoma (ACC)
Recurrent Adrenocortical Carcinoma (ACC)
Recurrent Abdominal Adrenocortical Carcinoma (ACC)
Carcinoma, Adrenocortical
Carcinoma, Adrenal Cortical

Conditions: Official terms:
Carcinoma
Adrenocortical Carcinoma
Recurrence

Conditions: Keywords:
external beam radiation therapy (EBRT)
abdominal adrenocortical carcinoma (ACC)
preoperative radiation
Mitotane
Maximum Tolerated Dose (MTD)
Surgical Resection
in-field intraabdominal progression-free survival (PFS)
out-of-field intraabdominal progression-free survival (PFS)
DNA damage repair markers
oxidative stress response

Study type: Interventional

Study phase: Phase 1

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Radiation
Intervention name: Preoperative external beam radiation therapy (EBRT)
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 DL3) based on assigned Cohort and Dose Level (DL). Cohorts are by mitotane status at enrollment: Cohort 1 (with detectable mitotane levels), Cohort 2 (never had or without detectable mitotane levels), Cohort 3 (either).
Arm group label: Preop RT + surgery

Intervention type: Procedure
Intervention name: Surgical resection
Description: Planned surgical resection (all participants) 4-8 weeks after completion of the preoperative radiotherapy (EBRT)
Arm group label: Preop RT + surgery

Summary: Background: The eyeGENE(R) program is a research resource for inherited eye conditions which includes genotypic and phenotypic data, imaging, and a corresponding biobank of DNA samples from people with a variety of eye diseases. Since 2007 this registry has been helping researchers learn more about the genetic sources for many inherited eye diseases. These findings helped them create better treatments. Now researchers want to expand eyeGENE(R) to include more people for certain eye diseases. Objective: To collect information and DNA samples for the study of eye diseases. Primary objective -To expand the current eyeGENE(R) data repository with targeted participant accrual Secondary objectives - To enhance recruitment for clinical trials and investigations in inherited eye diseases - To establish genotype-phenotype correlations for rare eye diseases Eligibility: People of any age with certain eye diseases. These can include aniridia; Best disease; blue-cone monochromacy; corneal dystrophy; and disorders of pigmentation, such as albinism. Relatives unaffected by the eye disease of interest may also be needed. Design: Researchers will select participants based on their diagnosis. The data may include images and test results from eye exams. Participants will provide a sample of saliva. They will receive a kit with written instructions. They will spit in a tube and mail it to the NIH. Participants may be asked to provide a blood sample. The blood may be drawn at the NIH or at a local clinic. The eyeGENE(R) repository will offer researchers data about the participants eye conditions. The data may include pictures of their eyes, results of genetic testing, and history of other diseases. Researchers will be able to see data such as age and gender, but they will not see names, dates of birth, or contact information.

Detailed description: Background: - Although surgical resection is the treatment of choice in participants with localized or regionalized primary and recurrent abdominal adrenocortical carcinoma (ACC), loco-regional recurrence following complete resection of ACC occurs in 50-80% of the participants, most commonly in the first five years postoperatively. - Retrospective single institutional series report improvement in local control with postoperative adjuvant radiotherapy (RT) in selected participants with ACC. - Preoperative RT is used in several abdominal and retroperitoneal malignancies to improve local control. There is no prospective data available for the use of this treatment approach for participants with resectable ACC. - We hypothesize that preoperative RT alone is safe and can result in a lower loco-regional recurrence in participants with resectable recurrent ACC with no peritoneal carcinomatosis. Thus, this phase I dose-escalation trial aims to evaluate the safety and feasibility of preoperative radiation in participants with resectable recurrent ACC. - Health-related quality of life (QOL) is a well-accepted tool to measure the outcome of cancer treatments. SF-36 v2 questionnaire has been frequently used to evaluate the QOL in participants with cancer. There is no study evaluating the difference in QOL in participants with resectable recurrent ACC undergoing preoperative RT and surgery. Objectives: -To determine the maximum tolerated dose and the safety and toxicity profile of preoperative external beam radiation therapy (EBRT) with or without standard of care mitotane, before surgical resection in participants with resectable ACC Eligibility: - Age >= 18 years - Pathological confirmation of ACC with clinical evidence of abdominal recurrence - ECOG 0-2 - Surgically resectable disease at presentation with no or limited extra-abdominal disease and without ACC peritoneal carcinomatosis based on a diagnostic laparoscopy at screening. - The last dose of chemotherapy treatment except for mitotane more than 4 weeks prior to starting treatment with this protocol, and participants must have recovered from chemotherapy. - No prior abdominal radiation - No contraindication to abdominal radiotherapy Design: - This study will enroll up to 24 evaluable participants as follows: - Participants will be enrolled in Cohort 1 or 2 based on mitotane use or serum level. Up to 6-18 evaluable participants per these cohorts (i.e., resectable ACC with and without mitotane use) will be enrolled to assess the safety of 3-level dose-escalating preoperative EBRT. - Participants will be enrolled in Cohort 3 regardless of mitotane use or serum level, and will only start enrollment when we observe no DLTs in > 1 participant in Cohort 1 at Dose Level 1. Up to 12 evaluable participants will be enrolled in this cohort. - Preoperative assessment of QOL using a standardized questionnaire (SF-36 v2) will be obtained at baseline. - Participants will be treated with preoperative external beam radiation therapy (EBRT) daily 5 days/week (M-F), followed by a planned surgical resection, 4-8 weeks after the completion of EBRT. - A standard 3 + 3 design will be used to determine the MTD of dose-escalated EBRT, with 3 dose levels (DL1- 30 Gy delivered in 10 fractions, DL2-36 Gy in 12 fractions, DL3-42 Gy in 14 fractions). - Postoperative surveillance imaging studies and laboratory tests will be performed every 3 months in the first 3 years, then every 6 months thereafter in years 4-10. FDG-PET scan will be performed every 6 months postoperatively in the first 3 years, then every year in years 4-10. Additional assessments may be performed if clinically indicated.

Criteria for eligibility:
Criteria:
- INCLUSION CRITERIA: - Age >= 18 years - Pathological confirmation of ACC by the Laboratory of Pathology, NCI. Note: Confirmation may be done from archival sample; fresh tissue is not required unless otherwise acquired for clinical purposes. - Measurable disease by RECISTv1.1. criteria at enrollment - Evidence of recurrent ACC amenable to surgical resection that can be performed at NIH Clinical Center (CC) - Must be suitable for external beam radiotherapy AND surgery in the opinion of the treating investigator (e.g., based on clinical history and imaging) - Participants with metastatic ACC outside the area(s) to be exposed to investigational treatments (e.g., liver parenchyma, lung[s], or bone[s]) must have disease that is amendable for a complete resection and/or catheter-based and/or radiation-based ablation. - Mitotane therapy- Participants may be receiving mitotane currently, have received it in the past, or never have received mitotane. However, participants will be evaluated in separate cohorts based on mitotane use and, as enrollment is sequential, not all participants may be eligible for the study at all times. Note: Participants with a history of mitotane use may continue on study at the discretion of the treating investigator. Participants will not initiate mitotane on study. - Participants must agree to undergo tumor biopsy of easily accessible tumor sites prior to study treatment. - Performance Status (ECOG) 0-2 - Adequate organ function, including: - Hemoglobin >= 9.0 gm/dL - ANC >= 1,500/mm^3 - Platelets >= 75,000/mm^3 - AST and ALT <= 3 x Upper Limit Normal (ULN) - Bilirubin <= 2 x ULN - Creatinine within normal institutional limits or creatinine clearance >60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal calculated using eGFR. - Sexually-active participants of childbearing potential must agree to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) prior to and for 4 months following cytoreduction surgery. - Breastfeeding participants must agree to discontinue breastfeeding until 4 months following cytoreductive surgery. - Ability of participant to understand and willingness to sign a written informed consent document - Participants must agree to co-enroll in tissue collection protocol 09C0242 "Prospective comprehensive molecular analysis of endocrine neoplasms." EXCLUSION CRITERIA: - Primary ACC or suspicious/indeterminate adrenal tumor without pathological confirmation - Prior abdominal radiation therapy - Participants who have received chemotherapy, immunotherapy, investigational therapy, or radiotherapy treatment within the last 4 weeks prior to starting treatment and/or have not recovered from toxicities to less than grade 2 CTCAE. - Infection requiring parenteral antibiotics - Suspected or proven ACC peritoneal metastasis - Pre-existing known or suspected radiation sensitivity syndromes - Prohibitive condition(s) to diagnostic laparoscopy - Participants who have an unacceptable risk for a major surgical procedure such as participants with high risks for major cerebro-cardiovascular (such as those who had doxorubicin exposure as based on screening echocardiogram and ECG) and pulmonary complications and those with estimated perioperative mortality greater than 15% per ACS NSQIP Surgical Risk calculator. - Participants receiving other investigational therapies - Participant pregnancy - Active systemic infections, coagulation disorders, or other major medical illnesses such as uncontrolled diabetes mellitus, uncontrolled hypertension (persistently grade 2 or worse), active severe cerebro-cardio-pulmonary diseases, and acute major organ dysfunction. - Acute intraabdominal conditions such as obstruction or peritonitis at the time of the evaluation or surgery. - Evidence at screening of or currently active CNS metastasis within 6 months of EBRT; participants with history of treated brain metastases with intracranial recurrence within 6 months prior to treatment. Note: Participants with any signs or symptoms suggestive of previously undiagnosed brain metastasis at screening or with a history of brain metastasis should receive imaging at screening; otherwise, imaging is not required. - HIV-positive participants with CD4 below 200 or who are not on anti-retroviral therapy - Participants who have a history of another primary malignancy from which the participant has been disease-free for < 3 years at the time of enrollment.

Gender: All

Minimum age: 18 Years

Maximum age: 120 Years

Healthy volunteers: No

Locations:

Facility:
Name: National Institutes of Health Clinical Center

Address:
City: Bethesda
Zip: 20892
Country: United States

Contact:
Last name: National Cancer Institute Referral Office

Phone: 888-624-1937
Email: ncimo_referrals@mail.nih.gov

Start date: November 17, 2024

Completion date: December 1, 2040

Lead sponsor:
Agency: National Cancer Institute (NCI)
Agency class: NIH

Source: National Institutes of Health Clinical Center (CC)

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06487481
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001587-C.html