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

NCT06487481 | Recruiting Phase 1

• 2 other identifiers: 10001587001587-C
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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

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

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

Outcome Measures

Primary Outcomes (1)

• 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

  Fraction of participants with a dose-limiting toxicity (DLT) will be reported at each dose level

  from the start of RT and for 30 days after its completion

Secondary Outcomes (5)

• Determine the 30-day postoperative complications per Clavien-Dindo classification

  baseline, until 30 days after cytoreductive surgery

• Determine the objective response of ACC within the radiation treatment field per RECIST criteria

  baseline, every 3-6 months after cytoreductive surgery for up to 10 years after surgery

• Assess in-field intraabdominal progression-free survival (PFS)

  baseline, every 3-6 months after cytoreductive surgery for up to 10 years after surgery

• Determine overall survival (OS) through 10 years postoperatively

  baseline, every 3-6 months after cytoreductive surgery for up to 10 years after surgery

• Assess quality of life measured by Short Form-36 Health Survey version 1.0 (SF-36 V1) questionnaire

  baseline, 4 weeks after RT, and then 2 weeks, 4 weeks, 6 months and 12 months after surgery

Study Arms (1)

Preop RT + surgery

EXPERIMENTAL

Preoperative RT at escalating doses followed by surgical resection

Procedure: Surgical resection; Radiation: Preoperative RT

Interventions

Surgical resection PROCEDURE

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

Preop RT + surgery

Preoperative RT RADIATION

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).

Preop RT + surgery

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Adrenocortical Carcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Study Officials

• Naris Nilubol, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristine J Villaruel

CONTACT

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

Naris Nilubol, M.D.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2024
• First Posted: July 5, 2024
• Study Start (Estimated): May 11, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2040
• Last Updated: May 6, 2026

Record last verified: 2026-03-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested from other researchers within 10 years after the completion of the primary endpoint by contacting the Principal Investigator.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)