AZD1390 and Stereotactic Body Radiation Therapy for the Treatment of Metastatic Solid Tumor Cancers

Inclusion Criteria

• Willing and able to provide written informed consent
• Aged at least 18 years
• Karnofsky performance score (KPS) of >= 60
• Histologically confirmed diagnosis of cancer with clear evidence of metastasis on imaging. Confirmation of metastasis by biopsy is preferred but not required
• Candidates for SBRT delivered as 6 Gy x 5 daily fractions to 2 sites of disease. The radiation plan should meet departmental guidelines. Patients can have more than 2 sites of disease. If patient requires radiation therapy (RT) to other sites of disease this can be done after completion of dose-limiting toxicity (DLT) period
• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
• Platelets >= 75 x 10^9/L
• Hemoglobin >= 8 g/dL
• Total bilirubin =< 1.5 times the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 times the ULN if no liver involvement or =< 5 times the ULN with liver involvement with metastatic disease
• Creatinine < 1.5 times ULN concurrent with creatinine clearance > 50 mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is > 1.5 times ULN
• Lipase within normal limits (WNL)
• Creatine kinase (CK) =< 5 times ULN
• Females of childbearing potential must have a negative pregnancy test during screening and must not be breastfeeding or intending to become pregnant during the study. Male patients with female partners of child-bearing potential must be willing to use two forms of acceptable contraception, including one barrier method, during their participation in this study and for 16 weeks following the last dose of the study drug
• Ability to swallow and retain oral medication

Exclusion Criteria

• Prior radiotherapy to the same region within the last 3 months
• Ongoing treatment for brain metastases. Patients with brain metastases may participate in this trial however, treatment for brain metastases will have to be completed prior to study enrollment. Treatments can begin or resume two weeks after completing protocol therapy
• History of epileptic disorder
• For Arm B patients with cancers involving the spinal cord, the length of the spinal cord lesion requiring palliative treatment is greater than 10 cm
• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
• Evidence of established ILD on screening CT scan
• Evidence of severe pulmonary infections, as judged by the investigator, based on clinical findings and investigations
• Concurrent severe and/or uncontrolled medical condition (e.g., severe chronic obstructive pulmonary disease [COPD])
• Cardiac dysfunction defined as: Myocardial infarction within six months of study entry, New York Heart Association (NYHA) class II/III/IV heart failure, unstable angina or unstable cardiac arrhythmias
• Any of the following cardiac criteria: * Any factors that increase the risk of corrected QT interval (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age. Patients stable on concomitant medications known to prolong the QT interval may be allowed to participate in the study provided that their mean resting corrected QT interval (Fridericia's correction formula [QTcF]) is < 470 msec at baseline
• History or presence of myopathy or raised creatine kinase (CK) > 5 x ULN on 2 occasions at screening
• Anticancer therapy within 7 days of first SBRT. These treatments should also be held for 7 days after last dose of SBRT. Patients who have received an immune checkpoint inhibitor within 28 days of first administration of study therapy will be excluded
• History of hypersensitivity to AZD1390 and excipients or drugs with a similar chemical structure or class to AZD1390
• Patients receiving treatment with strong inhibitors or inducers of CYP3A4 within 2 weeks before the first dose of AZD1390
• Patients who require sensitive substrates of BCRP, OATP1B1, MATE1, MATE2K and P-gp such as prazosin, cimetidine, simvastatin, dofetilide, metformin, dabigatran, digoxin and fexofenadine should be avoided while on study