A Study of Reduced-dose Radiation in People With Metastatic Tumors With a Genetic Change

Phase II Study to Examine Precision Radiation in Patients With Pathogenic Mutations in ATM

This study will test whether reduced-dose radiotherapy is an effective treatment for metastatic tumors with an ATM mutation. The researchers want to find the lowest dose of radiation that would still be effective to treat these tumors.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Cancer
• Intervention / Treatment: Radiation: Palliative radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Daniel Gomez, MD; Phone Number: 212-639-2087
• Study Contact Backup: Name: Amy Xu, MD, PhD; Phone Number: 646-888-6863; Email: xua@mskcc.org

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (All protocol activities)
      • Contact: Amy Xu, MD, PhD; Phone Number: 646-888-6863
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (All protocol activities)
      • Contact: Amy Xu, MD, PhD; Phone Number: 646-888-6863
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (All protocol activities)
      • Contact: Amy Xu, MD, PhD; Phone Number: 646-888-6863
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Commack (All protocol activities)
      • Contact: Amy Xu, MD, PhD; Phone Number: 646-888-6863
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (All protocol activities)
      • Contact: Amy Xu, MD, PhD; Phone Number: 646-888-6863
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All protocol activities)
      • Principal Investigator: Amy Xu, MD, PhD
      • Contact: Daniel Gomez, MD; Phone Number: 212-639-2087
      • Contact: Amy Xu, MD, PhD; Phone Number: 646-888-6863
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (All protocol activities)
      • Contact: Amy Xu, MD, PhD; Phone Number: 646-888-6863

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed malignancy with at least one metastatic lesion referred for palliative radiotherapy
• Pathogenic mutation in ATM (somatic and germline allowed)
• 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 CNS disease and cord compression, and areas in which re-irradiation would not be feasible, including spinal cord overlap.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: radiation; Subjects will receive reduced dose radiation to radiographically progressive lesions identified on imaging (including asymptomatic bone metastases). The study uses a prespecified 2-stage design with early stopping after the first stage to evaluate whether treatment-failure rates are acceptably low relative to a historical benchmark.

Radiation: Palliative radiotherapy; Initial cohort (stage 1) of patients will receive 4Gy x 2. They will be re-evaluated at 2 and 6 months (+/- 2 weeks). Accounting for anticipated survival times of these patients, we expect to have 12 evaluable patients from 20 enrolled patients. For stage 2 dose reduction will be explored across two palliative regimens, with timepoint for local failure adjusted accordingly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment failure rate of irradiated lesion	Defined as (i) radiographic progression or (ii) re-irradiation to the treated site. If PET is performed, radiographic criteria will be evaluated per PERCIST	up to 12 months

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Amy Xu, MD, PhD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2021
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: August 11, 2021
• First Submitted That Met QC Criteria: August 12, 2021
• First Posted (Actual): August 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Reduced-dose Radiation; Pathogenic Mutations; ATM (ataxia telangiectasia mutated); 21-310
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Neoplasms; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Neoplastic Processes; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Hereditary Sensory and Autonomic Neuropathies
• Other Study ID Numbers: 21-310

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No