Y-90, Capecitabine, and Atezolizumab for Oligometastatic CRC

Inclusion Criteria

• •1. Histologically confirmed diagnosis of colorectal adenocarcinoma
• •2. Surgically unresectable, liver-isolated or liver-dominant, RECIST measurable, metastatic disease
• •3. Age ≥18 years at the time of signing informed consent
• •4. ECOG performance status 0 or 1
• •5. Progression on 2 or more lines of systemic therapy
• •6. Agreeable to providing tumor tissue and blood for exploratory correlative analyses
• •7. Less than 50% of liver volume replaced by metastatic disease (as determined by investigator)
• •8. Demonstrate adequate organ function as defined in table below (all screening labs should be performed within 14 days of atezolizumab initiation):
• •Hematologic Absolute neutrophil count (ANC) ≥1,500 /mcL or ≥1,200 /mcL for those with benign ethnic neutropenia Absolute Lymphocyte Count (ALC) ≥ 0.5 x 109/L (500/uL) Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L within 7 days of assessment. Patient may be transfused or receive EPO to meet this criterion
• •Renal Serum creatinine OR measured or calculated creatinine clearance ≤1.5 X upper limit of normal (ULN) OR (GFR can also be used in place of creatinine or CrCl) ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• •Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 5 X ULN Alkaline Phosphatase ≤ 5 X ULN Albumin ≥2.5 mg/dL
• •Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• •≤1.5 X ULN unless subject is receiving anticoagulant therapy. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• •Creatinine clearance should be calculated per institutional standard. Exceptions can be made for patients with known Gilbert disease (≤ 3X ULN)
• •9. Female subjects of childbearing potential must be willing to use an adequate method of contraception from the time of the negative pregnancy test until a minimum of 6 months after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive (injectable or implantable), or intrauterine device in conjunction with a barrier method. Breast feeding subjects must be willing to discontinue at treatment start and for 5 months post-treatment.
• •10. Male subjects of childbearing potential must agree to use an adequate method of contraception with female partners of childbearing potential including abstinence or condoms plus an additional contraceptive method such as hormonal contraceptive (injectable or implantable), or intrauterine device during the study and for up to 3 months after the last dose of study drug.
• •11. Ability to understand and the willingness to sign a written informed consent document and to comply with the study protocol procedures
• •22. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 28 days before the first dose of atezolizumab.
• •23. Any major surgery or significant traumatic injury within 28 days of initiating study treatment or anticipation of need for a major surgical procedure during the study
• •24. Evidence of other significant or uncontrolled medical or psychiatric conditions that could affect compliance with the protocol
• •25. Pregnancy, breast-feeding, or prisoner status
• •26. History of leptomeningeal disease
• •27. Uncontrolled tumor-related pain
• •28. Patients requiring pain medication must be on a stable regimen at study entry.
• •29. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
• •Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
• •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
• •• Patients with indwelling catheters (e.g., PleurX) are allowed.
• •30. Uncontrolled or symptomatic hypercalcemia (ionized calcium 1.5 mmol/L, calcium 12 mg/dL or corrected serum calcium ULN)
• •31. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• •• History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• •32. Prior allogeneic stem cell or solid organ transplantation
• •33. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• •34. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment