SBRT with MRI Guidance in Treating Patients with Liver Metastases

Inclusion Criteria

• For phase I trial, have a diagnosis of histologically confirmed or clinically suspected metastatic cancer to the liver; for phase IB trial have a diagnosis of histologically confirmed or clinically suspected metastatic colorectal carcinoma (CRC) to the liver
• Patient must be a candidate for SBRT to at least one intrahepatic lesion but no more than 6 intrahepatic lesions
• Patient must be a candidate for treatment on the ViewRay treatment unit. Must be screened to rule out implants and devices that are not MRI compatible
• Be willing and able to provide written informed consent
• Patients may be therapy-naive or have had prior systemic therapy up to two weeks prior to study entry
• No active central nervous system (CNS) metastatic disease. NOTE: Subjects with CNS involvement must meet ALL of the following to be eligible: * At least 28 days from prior definitive treatment of their CNS disease by surgical resection, SBRT or whole body radiation therapy (WBRT) at the time of registration * AND asymptomatic and off systemic corticosteroids and/or enzyme-inducing antiepileptic medications for brain metastases for > 14 days prior to registration
• Platelet count >= 50,000/uL (performed within 28 days of SBRT treatment initiation)
• Absolute neutrophil count (ANC) >= 1000/uL (performed within 28 days of SBRT treatment initiation)
• Hemoglobin (Hgb) >= 8 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 28 days of SBRT treatment initiation)
• Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) creatinine/calculated creatinine clearance (CrCl) >= 30 mL/min for subject with creatinine levels > 1.5 X institutional upper limit of normal (ULN) (performed within 28 days of SBRT treatment initiation)
• Bilirubin =< 1. 5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 28 days of SBRT treatment initiation)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x ULN (performed within 28 days of SBRT treatment initiation)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastic time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 28 days of SBRT treatment initiation)
• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 28 days of SBRT treatment initiation)
• For patients enrolled on the liver dose escalation arm, screening labs must be consistent with Child Pugh class A unless therapeutic anticoagulation places them in Child Pugh B. In that case, trial entry or exclusion will be at the discretion of the treating physician
• Have a performance status of 2 or less on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Life expectancy of > 12 weeks
• Women of childbearing potential (WOCP) should have a negative urine or serum pregnancy test prior to initiation of radiation therapy. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• WOCP must not be pregnant or breast-feeding
• WOCP must be willing to use an effective method of birth control such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence for the duration of the radiotherapy and 60 days thereafter * NOTE: A person of childbearing potential is anyone (regardless of sexual orientation, gender identity, having undergone a tubal ligation, or remaining celibate by choice) who was born with a uterus and at least one ovary and meets both of the following criteria: ** Is post-menarcheal (i.e., has had at least one prior menses) ** Has not undergone a hysterectomy or bilateral oophorectomy or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

Exclusion Criteria

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the initiation of SBRT
• History of a second invasive cancer in the last 3 years (except for appropriately treated low-risk prostate cancer, treated non-melanoma skin cancer, appropriately treated ductal carcinoma in situ or early stage invasive carcinoma of breast appropriately treated in situ/early stage cervical/endometrial cancer
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with follow up scans or visits
• Has a primary tumor histology of germ cell tumor, leukemia, or lymphoma
• Has a primary liver cancer such as cholangiocarcinoma or hepatocellular carcinoma
• Has had prior radiation therapy that significantly overlaps with the liver
• Has a diagnosis of Crohn’s disease, ulcerative colitis, or scleroderma
• Patients with Gilbert’s disease or other primary disorders of bilirubin metabolism will not be allowed on the trial
• For patients in the liver dose escalation arm only, has pre-existing liver disease such that patients are classified as Child Pugh B or worse. If the patient is anti-coagulated such that their INR places them in the Child Pugh B (CP-B) classification, exclusion or inclusion will be at the discretion of the treating physician
• Pregnancy or women of childbearing potential and men who are sexually active and refuse to use medically acceptable forms of contraception
• Patients with implanted hardware that would preclude MRIs