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