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)
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
Single group
Surgical resection
Procedure/SurgeryPlanned surgical resection (all participants) 4 weeks after completion of the preoperative RT
Preoperative RT
RadiationPreoperative 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).
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
Determine the 30-day postoperative complications per Clavien-Dindo classification
Assessment of 30-day postoperative RT complications determined by Clavien-Dindo classification (frequency and and severity)
Determine the objective response of ACC within the radiation treatment field per RECIST criteria
Objective response determined by RECIST, results as fraction in evaluable participants and by 95% confidence interval of the median
Assess in-field intraabdominal progression-free survival (PFS)
In-field intraabdominal progression-free survival (PFS) determined by RECIST using the Kaplan-Meier method and by 95% confidence interval of the median
Determine overall survival (OS) through 10 years postoperatively
Overall survival (OS) up to 10 years postoperatively determined by RECIST using the Kaplan-Meier method and by 95% confidence interval of the median
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