Recruiting
Phase 1

EBRT

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06487481

Conditions

Adrenocortical Carcinoma (ACC)

Recurrent Adrenocortical Carcinoma (ACC)

Recurrent Abdominal Adrenocortical Carcinoma (ACC)

Carcinoma, Adrenocortical

Carcinoma, Adrenal Cortical

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Surgical resection

Preoperative RT

Study Details

Brief summary:

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.

Conditions

Adrenocortical Carcinoma (ACC)

Recurrent Adrenocortical Carcinoma (ACC)

Recurrent Abdominal Adrenocortical Carcinoma (ACC)

Carcinoma, Adrenocortical

Carcinoma, Adrenal Cortical

Study ID

NCT06487481

Start date

Sep 10, 2026

Status verified date

Mar 11, 2026

Completion date

Dec 1, 2040

Anticipated

Primary completion date

Dec 1, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

  • 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.
  • 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."

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 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.

Study Design

Enrollment

32 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Preop RT + surgery

Preoperative RT at escalating doses followed by surgical resection

Interventions

Surgical resection

Planned surgical resection (all participants) 4 weeks after completion of the preoperative RT

Preoperative RT

Preoperative RT at escalating doses in daily fractions over approximately 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).

Primary outcome measure

  • Determine the maximum tolerated dose (MTD) and safety and toxicity profile of preoperative external beam radiation therapy (RT) with or without standard-of-care mitotane, before surgical resection in participants with resectable recurrent ACC [ Time Frame: from the start of RT and for 30 days after its completion ]

Central Contacts and Locations

Central contacts

Kristine J Villaruel

(240) 858-7033kristinejoy.villaruel@nih.gov

Naris Nilubol, M.D.

(240) 760-6154niluboln@mail.nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

National Cancer Institute Referral Office

888-624-1937ncimo_referrals@mail.nih.gov

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 8, 2026

Last verified

Mar 11, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-08.