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A Study of Reduced-Dose Radiation in Patients with Metastatic Tumors with a Genetic Change
Trial Status: active
This phase II trial investigates whether reduced-dose radiation is an effective treatment in patients with ATM mutated tumors that have spread to other places in the body (metastatic), and whether reduced-dose radiation is sufficient to control local disease progression. Radiation delivered to metastatic tumors causes damage to the DNA (genetic information) in the cancer cells, which causes the cells to die. An ATM mutation reduces cancer cells’ ability to fix damage to their DNA, which makes it more likely that the radiation will kill the cells. Lower doses of radiation may cause fewer side effects than standard doses. Reduced-dose radiation therapy may help control the disease in patients with metastatic tumors with an ATM mutation.
Inclusion Criteria
Histologically confirmed malignancy with at least one metastatic lesion referred for palliative radiotherapy
Pathogenic mutation in ATM (somatic and germline allowed)
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Age >= 18 years
Able to provide informed consent
Patients at reproductive potential must agree to practice an effective contraceptive method during radiation treatments
Expected life expectancy of at least 6 months
Exclusion Criteria
Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances
Serious medical co-morbidities precluding radiotherapy
Pregnant or breast-feeding women
Lesions excluded from de-escalation include regions in which the risk of local disease progression is unacceptably high, including central nervous system (CNS) disease and cord compression, and areas in which re-irradiation would not be feasible, including spinal cord overlap
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05010031.
I. To assess the 6 month treatment failure rate in patients with pathogenic mutations in ATM treated with reduced dose radiotherapy.
SECONDARY OBJECTIVES:
I. To define 2 month treatment failure rate.
II. To determine treatment toxicity using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
III. To determine rate of reirradiation.
IV. To determine local progression free survival.
V. To assess time to change in systemic therapy.
VI. To determine overall survival.
VII. To determine the appropriate level of dose reduction.
VIII. To examine the impact of radiation therapy (RT) in monoallelic and biallelic mutants separately.
OUTLINE: Patients are assigned to 1 of 2 groups.
GROUP I (CLOSED TO ACCRUAL AS OF 1/21/2026): Patients undergo radiation therapy for 2 sessions. Patients may also undergo positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI) throughout study.
GROUP II: Patients undergo radiation therapy for 1 session. Patients may also undergo PET, CT and MRI throughout study.
After completion of study treatment, patients are followed up at 2, 6, and 12 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
