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

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Metastatic Cancer

Intervention / Treatment
-----------------
* Radiation: Palliative radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
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. Concomitant pathogenic mutation in p53 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm, phase II noninferiority, prospective trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: radiation<br>Subjects will receive reduced dose radiation to radiographically progressive lesions identified on imaging (including asymptomatic bone metastases). | Radiation: Palliative radiotherapy<br>* The first cohort of 26 evaluable patients will be treated with 4Gyx2, followed by a 6 month observation period post-RT to assess for treatment failures. If 7 or more failures are observed, cohort 1 will be closed and 4Gyx3 will be explored in the second cohort. If at most 6 failures are detected in the first cohort, dose will be further reduced to 4Gyx1 for the second cohort. Radiation therapy will be delivered according to department standards, including normal tissue constraints per hypofractionated guidelines. All techniques including conventional, 3D-CRT, or IMRT technique may be used. Image guidance at the time of treatment delivery to verify patient positioning may be chosen at the discretion of the treating radiation oncologist according to department standards.<br>|

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 | 6 month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pathogenic Mutations, ATM (ataxia telangiectasia mutated), 21-310, Reduced-dose Radiation