Inclusion Criteria:  Histologically confirmed diagnosis of cancer with clear evidence of metastasis on imaging. Subjects with locally advanced or recurrent (non-metastatic) cancer for whom palliative RT is indicated may also be enrolled. Scheduled to receive palliative RT delivered as 4 Gray × 5 daily fractions at the discretion of the treating radiation oncologist. The radiation plan should be designed to optimally limit the radiation dose delivered to normal tissues using conformal treatment plans and protocol-specified limits.  One or more of the following sites of metastasis:  Skin Subcutaneous or soft tissue Any other site that will allow the radiation dose to normal structures to remain within protocol-specified dosing limits. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. Male or female subjects at least 18 years of age who are willing and able to provide written informed consent. Other protocol-defined criteria may apply  Exclusion Criteria:  Prior radiotherapy to the same region within the last 6 months. Subjects who are currently receiving palliative RT for brain metastases. Subjects who have brain metastases may participate in this trial, if they are receiving palliative RT for cancer in a location other than the brain. For subjects with cancers involving the spinal cord, the length of the spinal cord requiring palliative treatment must be 10 cm or less. Subjects with bone marrow impairment as evidenced by hemoglobin <8.0 g/dL, neutrophil count <0.7 × 10^9/L, or platelets <80 × 10^9/L . History of difficulty swallowing, malabsorption or other chronic gastrointestinal disease or condition that may hamper compliance and/or absorption of XRD-0394, use of percutaneous endoscopic gastrostomy (PEG) tubes. Significant cardiac conduction abnormalities, including a history of long corrected QT (QTc) interval syndrome and/or pacemaker, or impaired cardiovascular function such as New York Heart Association classification >2. Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anticancer therapy within 14 days of first XRD-0394 dose. These treatments should also be held for a minimum of 14 days after completion of RT. Subjects receiving bleomycin within 30 days of the first dose of XRD-0394.  Subjects receiving treatment with any drug that is a strong inhibitor or inducer of cytochrome P450 (CYP) 3A4 enzyme activity or an inhibitor of breast cancer resistance protein (BCRP) within 14 days or 5 half-lives prior to screening (whichever is longer). In particular,  Glucocorticoids are inducers of CYP3A4. Therefore, dexamethasone, prednisone, or other glucocorticoids should not be administered within 14 days or 5 half-lives prior to screening (whichever is longer) and should only be initiated after the course of palliative RT is complete (and at least 24 hours after the administration of XRD-0394). Gefitinib and imatinib are inhibitors of BCRP. Therefore, these agents should not be administered within 14 days or 5 half-lives prior to screening (whichever is longer) and should be held for a minimum of 14 days after completion of RT. Participation in another investigational study of an unapproved drug or device or treatment with another ATM, DNA-PK, or ataxia-telangiectasia and Rad3-related (ATR) inhibitor within 28 days of the first dose of XRD-0394. Subjects who are pregnant or breast-feeding. Subjects with a QTc interval >450 msec (calculated using Fridericia's QT correction formula) at screening.