Atezolizumab in Combination with Cyclophosphamide, Sorafenib, and Bevacizumab for the Treatment of Recurrent or Refractory Solid Tumors in Pediatric Patients, ANGIO-A Study

Inclusion Criteria

• Patients must be >= 12 months and =< 30 years at the time of enrollment on study
• Willingness to enroll on the St. Jude Molecular Analysis of Solid Tumors (MAST) study
• (Part 1): Patients with refractory or recurrent (relapsed) solid tumors accessible by biopsy for which there is no standard therapy are eligible (If a bone marrow aspiration/biopsy is performed as part of the disease work-up, this must be completed within 14 days prior to the start of protocol therapy)
• (Part 2): Patients must have failed at least one prior systemic therapy and with one of the following diagnoses: * Biopsy accessible refractory or recurrent (relapsed) hepatocellular carcinoma * Biopsy accessible refractory or recurrent (relapsed) or FL-HCC, DSRCT or non-central nervous system (CNS) MRT (If a bone marrow aspiration/biopsy is performed as part of the disease work-up, this must be completed within 14 days prior to the start of protocol therapy)
• Performance level: Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age * Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Disease status: Patients must tumors that are unresectable and have either measurable or evaluable disease that is accessible by biopsy (If a bone marrow aspiration/biopsy is performed as part of the disease work-up, this must be completed within 14 days prior to the start of protocol therapy. All tumor imaging must be performed within 14 days to the start of protocol therapy)
• Patients with solid tumor not metastatic to bone marrow: * Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3 * Platelet count >= 75,000/mm^3 (no transfusion within 7 days of enrollment) * Hemoglobin >= 8 g/dL (with or without support) (Must be performed within 7 days prior to enrollment; Laboratory tests need not be repeated if therapy starts within 7 days of obtaining labs to assess eligibility. If a post-enrollment lab value is outside the limits of eligibility, or laboratory values are older than 7 days, then the following laboratory evaluations must be re-checked within 72 hours prior to initiating therapy: complete blood count differential (CBCD), creatinine, bilirubin and alanine aminotransferase [ALT])
• Patients with solid tumor metastatic to bone marrow will be eligible for study but not evaluable for hematologic toxicity. These patients must not be known to be refractory to red cell or platelet transfusions. At least 2 of every cohort of 3 patients must be evaluable for hematologic toxicity. If dose limiting hematologic toxicity is observed at any dose level, all subsequent patients enrolled must be evaluable for hematologic toxicity
• Adequate renal function defined as serum creatinine based on age or creatinine clearance or radioisotope glomerular filtration rate GFR >= 50 ml/min/1.73m^2 (GFR >=40 ml/min/1.73m^2 if < 2 years of age) * Age: 1 months to < 6 months; maximum serum creatinine (mg/dL): 0.4 mg/dl (male and female) * Age: 6 months to < 1 year; maximum serum creatinine (mg/dL): 0.5 mg/dl (male and female) * Age: 1 to < 2 years; maximum serum creatinine (mg/dL): 0.6 mg/dl (male and female) * Age: 2 to < 6 years; maximum serum creatinine (mg/dL): 0.8 mg/dl (male and female) * Age: 6 to < 10 years; maximum serum creatinine (mg/dL): 1.0 mg/dl (male and female) * Age: 10 to < 13 years; maximum serum creatinine (mg/dL): 1.2 mg/dl (male and female) * 13 to < 16 years; maximum serum creatinine (mg/dL): 1.5 mg/dl (male) and 1.4 mg/dl (female) * Age: >= 16 years; maximum serum creatinine (mg/dL): 1.7 mg/dl (male) and 1.4 mg/dl (female) (Must be performed within 7 days prior to enrollment; Laboratory tests need not be repeated if therapy starts within 7 days of obtaining labs to assess eligibility; If a post-enrollment lab value is outside the limits of eligibility, or laboratory values are older than 7 days, then the following laboratory evaluations must be re-checked within 72 hours prior to initiating therapy: CBCD, creatinine, bilirubin and ALT)
• Adequate hepatic function defined as total bilirubin =< 5x upper limit of normal (ULN) and aspartate aminotransferase (AST)/ALT =< 3 x ULN for age (Must be performed within 7 days prior to enrollment; Laboratory tests need not be repeated if therapy starts within 7 days of obtaining labs to assess eligibility. If a post-enrollment lab value is outside the limits of eligibility, or laboratory values are older than 7 days, then the following laboratory evaluations must be re-checked within 72 hours prior to initiating therapy: CBCD, creatinine, bilirubin and ALT)
• Adequate cardiac function defined as shortening fraction >= 28% OR ejection fraction of ≥ 47% by echocardiogram
• QTc < 480 msec
• Adequate blood clotting defined as prothrombin time (PT)/ partial thromboplastin time (PTT) < 1.2 x ULN without factor replacement products for 7 days (Must be performed within 7 days prior to enrollment; Laboratory tests need not be repeated if therapy starts within 7 days of obtaining labs to assess eligibility. If a post-enrollment lab value is outside the limits of eligibility, or laboratory values are older than 7 days, then the following laboratory evaluations must be re-checked within 72 hours prior to initiating therapy: CBCD, creatinine, bilirubin and ALT)
• Females of childbearing potential and males able to father a child must be willing to practice acceptable methods of birth control to prevent pregnancy during the study and for at least 1 year after last dose of therapy
• Patients must have fully recovered from the acute toxic effects of chemotherapy, immunotherapy, surgery, or radiotherapy prior to entering this study: * Myelosuppressive chemotherapy: Patient has not received myelosuppressive chemotherapy within 1 week of enrollment onto this study (within 2 weeks of estimated therapy start date) (4 weeks if prior nitrosourea) * Hematopoietic growth factors: At least 7 days must have elapsed since the completion of therapy with a growth factor. At least 14 days must have elapsed after receiving pegfilgrastim * Biologic (anti-neoplastic agent): At least 7 days must have elapsed since completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur * Monoclonal antibodies: At least 14 days (at least 21 days from estimated therapy start date) must have elapsed since the completion of therapy with a monoclonal antibody * Radiotherapy: At least 1 week (at least 2 weeks from estimated therapy start date) must have elapsed since any irradiation; at least 5 weeks (at least 6 weeks from estimated therapy start date) must have elapsed since craniospinal RT or substantial bone marrow irradiation * Chemoembolization: at least 21 days (at least 28 from estimated therapy start date) must have elapsed since the completion of chemoembolization * Radioembolization: at least 21 days (at least 28 days from estimated therapy start date) must have elapsed since the completion of radioembolization
• Anticoagulants: Patients must not be on therapeutic anticoagulation including systemic thrombolytic agents, heparin, low molecular weight heparin, warfarin, or oral direct anticoagulants within 1 week of study entry. Prophylactic anticoagulants (i.e., intraluminal heparin to maintain patency of indwelling intravenous [IV] catheters) are allowed. Patients on prophylactic low molecular weight heparin (LMWH) due to history of thrombosis > 3months ago that has been adequately treated/resolved but remain on prophylaxis will be allowed
• Antipyretics and nonsteroidal anti-inflammatory medications: Must not have received medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase-2 (COX-2) activity (i.e., all antipyretic and anti- inflammatory medications except acetaminophen) within 1 week prior to study entry
• Cytochrome P450 enzyme-inducing medications: Must not be taking any of the following medications known to induce cytochrome P450 enzyme CYP3A4 within 1 week prior to study entry: St. John’s Wort, phenytoin, phenobarbital, felbamate, primidone, oxcarbazepine, carbamazepine, rifampin, and dexamethasone
• Cardiac disease or hypertension: Patients must not have a history of myocardial infarction, severe or unstable angina, or severe peripheral vascular disease. Hypertension must be well controlled on stable doses of medication for at least two weeks
• Female participant who is post-monarchal must have a negative urine or serum pregnancy test
• Life expectancy of at least 8 weeks

Exclusion Criteria

• Pregnant or breastfeeding
• Currently receiving other investigational drugs
• Unwilling or unable to comply with the safety monitoring requirements of this protocol
• Tumor not safely accessible by biopsy
• Inability or unwillingness of research participant or legal guardian / representative to give written informed consent
• Surgical procedures and serious or non-healing wounds: patients with a documented, chronic non-healing wound, ulcer, or bone fracture or history of a major surgical procedure or significant traumatic injury within 28 days prior to beginning therapy are excluded due to preclinical evidence supporting the potential for delayed wound healing. Minor surgical procedures for minimally invasive biopsies will be allowed. For minor surgeries, the wound must be healed, and 7 days elapsed since surgery. For procedures such as the placement of an indwelling IV catheter, it is recommended that bevacizumab be postponed for at least 24 hours after the procedure
• Thrombosis: Patients must not have a deep venous or arterial thrombosis (including pulmonary embolism) within the last three months prior to study entry and must not have a known thrombophilic condition (i.e., protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome)