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

Eligibility 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.