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

Phase 1

Recruiting

• Conditions: Carcinoma, Adrenocortical; Recurrent Adrenocortical Carcinoma (ACC); Carcinoma, Adrenal Cortical; Recurrent Abdominal Adrenocortical Carcinoma (ACC); Adrenocortical Carcinoma (ACC)

• Registration Number: NCT06487481
• Lead Sponsor: National Cancer Institute (NCI)

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.

Detailed Description

Background:

* Although surgical resection is the treatment of choice in participants with localized or regionalized primary and recurrent abdominal adrenocortical carcinoma (ACC), loco-regional recurrence following complete resection of ACC occurs in 50-80% of the participants, most commonly in the first five years postoperatively.

* Retrospective single institutional series report improvement in local control with postoperative adjuvant radiotherapy (RT) in selected participants with ACC.

* Preoperative RT is used in several abdominal and retroperitoneal malignancies to improve local control. There is no prospective data available for the use of this treatment approach for participants with resectable ACC.

* We hypothesize that preoperative RT alone is safe and can result in a lower loco-regional recurrence in participants with resectable recurrent ACC with no peritoneal carcinomatosis. Thus, this phase I dose-escalation trial aims to evaluate the safety and feasibility of preoperative RT in participants with resectable recurrent ACC.

* Health-related quality of life (QOL) is a well-accepted tool to measure the outcome of cancer treatments. SF-36 V1 questionnaire has been frequently used to evaluate the QOL in participants with cancer. There is no study evaluating the difference in QOL in participants with resectable recurrent ACC undergoing preoperative RT and surgery.

Objectives:

-To determine the maximum tolerated dose and the safety and toxicity profile of preoperative external beam RT with or without standard of care mitotane, before surgical resection in participants with resectable ACC

Eligibility:

* Age \>= 18 years

* Pathological confirmation of ACC with clinical evidence of abdominal recurrence

* ECOG 0-2

* Surgically resectable disease at presentation with no or limited extra-abdominal disease and without ACC peritoneal carcinomatosis based on a diagnostic laparoscopy at screening.

* The last dose of chemotherapy treatment except for mitotane more than 4 weeks prior to starting treatment with this protocol, and participants must have recovered from chemotherapy.

* No prior abdominal RT

* No contraindication to abdominal RT

Design:

* This study will enroll up to 24 evaluable participants as follows:

* Participants will be enrolled in Cohort 1 or 2 based on mitotane use or serum level. Up to 6-18 evaluable participants per these cohorts (i.e., resectable ACC with and without mitotane use) will be enrolled to assess the safety of 3-level dose-escalating preoperative RT.

* Participants will be enrolled in Cohort 3 regardless of mitotane use or serum level, and will only start enrollment when we observe no DLTs in \> 1 participant in Cohort 1 at Dose Level 1. Up to 12 evaluable participants will be enrolled in this cohort.

* Preoperative assessment of QOL using a standardized questionnaire (SF-36 V1) will be obtained at baseline.

* Participants will be treated with preoperative RT, followed by a planned surgical resection, 4 weeks after the completion of RT.

* A standard 3 + 3 design will be used to determine the MTD of dose-escalated RT, with 3 dose levels (DL1- 30 Gy delivered in 10 fractions, DL2-36 Gy in 12 fractions, DL3-42 Gy in 14 fractions).

* Postoperative surveillance imaging studies and laboratory tests will be performed every 3 months in the first 3 years, then every 6 months thereafter in years 4-10. FDG-PET scan will be performed every 6 months postoperatively in the first 3 years, then every year in years 4-10. Additional assessments may be performed if clinically indicated.

Study Timeline

• Study First Submitted: 2024-07-03
• Study First Submitted QC: 2024-07-03
• Study First Posted: 2024-07-05
• Status Verified: 2025-08-29
• Last Update Submitted: 2025-09-08
• Last Update Posted: 2025-09-09
• Study Start: 2025-09-14
• Primary Completion: 2030-12-01
• Study Completion: 2040-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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	from the start of RT and for 30 days after its completion	Fraction of participants with a dose-limiting toxicity (DLT) will be reported at each dose level

Secondary Outcome Measures

Name	Time	Method
Determine the 30-day postoperative complications per Clavien-Dindo classification	baseline, until 30 days after cytoreductive surgery	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	baseline, every 3-6 months after cytoreductive surgery for up to 10 years after surgery	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)	baseline, every 3-6 months after cytoreductive surgery for up to 10 years after surgery	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	baseline, every 3-6 months after cytoreductive surgery for up to 10 years after surgery	Overall survival (OS) up to 10 years postoperatively determined by RECIST using the Kaplan-Meier method and by 95% confidence interval of the median
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	Quality of life (QOL) measured by SF-36 V1 questionnaire evaluated using appropriate paired tests and descriptive results

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States