Study of Preoperative Radiation Therapy in Participants With Resectable Recurrent Abdominal Adrenocortical Carcinoma
- Conditions
- Carcinoma, AdrenocorticalRecurrent Adrenocortical Carcinoma (ACC)Carcinoma, Adrenal CorticalRecurrent Abdominal Adrenocortical Carcinoma (ACC)Adrenocortical Carcinoma (ACC)
- Interventions
- Radiation: Preoperative external beam radiation therapy (EBRT)Procedure: Surgical resection
- 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 radiation therapy (external beam radiation therapy \[EBRT\]) 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.
EBRT comes from a machine that aims radiation at tumors. Participants will receive EBRT 5 days a week for 2 to 3 weeks. Visits will last 30 to 60 minutes.
Participants will undergo surgery to remove their tumors 4 to 8 weeks after they finish EBRT. 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 radiation 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 v2 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 radiation therapy (EBRT) 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 radiation
* No contraindication to abdominal radiotherapy
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 EBRT.
* 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 v2) will be obtained at baseline.
* Participants will be treated with preoperative external beam radiation therapy (EBRT) daily 5 days/week (M-F), followed by a planned surgical resection, 6-8 weeks after the completion of EBRT.
* A standard 3 + 3 design will be used to determine the MTD of dose-escalated EBRT, 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.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 32
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Preop RT + surgery Preoperative external beam radiation therapy (EBRT) Preoperative radiotherapy at escalating doses followed by surgical resection Preop RT + surgery Surgical resection Preoperative radiotherapy at escalating doses followed by surgical resection
- Primary Outcome Measures
Name Time Method Determine the maximum tolerated dose (MTD) and safety and toxicity profile of preoperative external beam radiation therapy (EBRT) with or without standard-of-care mitotane, before surgical resection from the start of EBRT 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 Assess quality of life measured by Short Form-36 Health Survey version 2.0 (SF-36 v2) questionnaire baseline, 6 weeks after EBRT, and then 2 weeks, 6 weeks, 6 months and 12 months after surgery Quality of life (QOL) measured by SF-36 v2 questionnaire evaluated using appropriate paired tests and descriptive results
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 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 the objective response of ACC in the field of radiation 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
Determine the 6 weeks postoperative complications per Clavien-Dindo classification baseline, until 6 weeks after cytoreductive surgery Assessment of 30-day postoperative EBRT complications determined by Clavien-Dindo classification (frequency and and severity)
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States