RECRUITING

Study of Preoperative Radiation Therapy in Participants With Resectable Recurrent Abdominal Adrenocortical Carcinoma

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Background: Adrenocortical carcinoma (ACC) is a rare cancer of the adrenal glands. ACC often returns after tumors are removed with surgery. Less than 35% of people with ACC survive 5 years after diagnosis. Objective: To test a new type of external beam RT before surgery in people with ACC. Eligibility: People aged 18 years and older with ACC that came back after treatment but may be safely removed with surgery. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of their heart function. They will have imaging scans. A small sample of tumor tissue may be collected if one is not available. They will undergo laparoscopy: Small incisions will be made in the abdomen so that a thin tube with a light and camera can be inserted to view the organs. RT comes from a machine that aims radiation at tumors. Participants will receive preoperative RT in daily fractions over approximately 2-3 weeks, followed by a planned surgical resection about 4 weeks after the completion of RT. Visits will last 30 to 60 minutes. Participants will undergo surgery to remove their tumors about 4 weeks after they finish RT. They will stay in the hospital 1 to 3 weeks after surgery. Participants will have follow-up visits for 10 years after surgery.

Official Title

A Phase I Dose-escalation Study of Preoperative Radiation Therapy in Participants With Resectable Recurrent Abdominal Adrenocortical Carcinoma

Quick Facts

Study Start:2025-09-08

Study Completion:2040-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06487481

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 120 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * Individuals of childbearing potential must agree to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) prior to RT and continue until at least 4 months following cytoreduction surgery. * Nursing (including breastfeeding) participants must agree to discontinue nursing prior to RT and continue until at least 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."	* 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 RT; 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.

Inclusion Criteria

Exclusion 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.
* Individuals of childbearing potential must agree to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) prior to RT and continue until at least 4 months following cytoreduction surgery.
* Nursing (including breastfeeding) participants must agree to discontinue nursing prior to RT and continue until at least 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."

* 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 RT; 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.

Contacts and Locations

Study Contact

Kristine J Villaruel

CONTACT

(240) 858-7033

kristinejoy.villaruel@nih.gov

Naris Nilubol, M.D.

CONTACT

(240) 760-6154

niluboln@mail.nih.gov

Principal Investigator

Naris Nilubol, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Naris Nilubol, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-09-08

Study Completion Date2040-12-01

Study Record Updates

Study Start Date2025-09-08

Study Completion Date2040-12-01

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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