Stereotactic Body Radiation Therapy and Atezolizumab in Treating Patients with Recurrent, Persistent, or Metastatic Cervical, Vaginal, or Vulvar Cancer

Inclusion Criteria

• Ability to understand and the willingness to sign a written informed consent document
• Patients must have recurrent, persistent, or metastatic cervical cancer including squamous cell, adenocarcinoma and adenosquamous histologies or recurrent, persistent, or metastatic p16+ cancer of the vagina or vulva
• Age >= 18 years at time of signing informed consent form
• Ability to comply with the study protocol, in the investigator’s judgment
• All patients must have at least 2 distinct lesions as documented by imaging studies within 4 weeks prior to randomization
• Measurable disease per Immune-Modified Response Evaluation Criteria in Solid Tumors (irRECIST) * Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation * Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm (>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Consent to biopsy of metastatic site or consent to retrieval of archival tissue
• A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report prior to study enrollment. If a biopsy is not obtained, archival tissue should be obtained. If attempts to obtain archival tissue are unsuccessful, the patient may be enrolled
• Eastern Cooperative Oncology Group (ECOG) =< 2
• Life expectancy >= 3 months
• Absolute neutrophil count >= 1.5 x 10^9/L (1500/uL) (obtained within 21 days prior to initiation of study treatment) without granulocyte colonystimulating factor support
• Lymphocyte count >= 0.5 x 10^9/L (500/uL) (obtained within 21 days prior to initiation of study treatment)
• Platelet count >= 100 x 10^9/L (50,000/uL) (obtained within 21 days prior to initiation of study treatment); patients may be transfused to meet this criterion
• Hemoglobin >= 80 g/L (8 g/dL) (obtained within 21 days prior to initiation of study treatment); patients may be transfused to meet this criterion
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase =< 3 x upper limit of normal (ULN) (obtained within 21 days prior to initiation of study treatment), with the following exceptions: * Patients with documented liver metastases: AST and ALT =< 5 x upper limits of normal (ULN) * Patients with documented liver or bone metastases: alkaline phosphatase =< 5 x ULN
• Serum bilirubin =< 1.5 x ULN with the following exception: * Patients with known Gilbert disease: serum bilirubin level =< 3 x ULN (obtained within 21 days prior to initiation of study treatment)
• Serum creatinine =< 1.5 x ULN or creatinine clearance >= 40 mL/min (obtained within 21 days prior to initiation of study treatment) (calculated using the Cockcroft-Gault formula)
• Serum albumin >= 25 g/L (2.5 g/dL) (obtained within 21 days prior to initiation of study treatment)
• For patients not receiving therapeutic anticoagulation: international normalized ratio (INR) or activated partial thromboplastin time (aPTT) =< 1.5 x ULN (obtained within 21 days prior to initiation of study treatment)
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after last dose of atezolizumab. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately * A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus) * Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception

Exclusion Criteria

• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Active autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune thyroid disease, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren’s syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions: * Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study * Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: * Rash must cover < 10% of body surface area * Disease is well controlled at baseline and requires only low-potency topical corticosteroids * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• 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
• Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must have: * A stable regimen of highly active anti-retroviral therapy (HAART) * No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections * A CD4 count above 250 cells/uL and an undetectable HIV viral load on standard polymerase chain reaction-based tests
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease * Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBs [antibody to hepatitis B core antigen] antibody test) are eligible * Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
• Active tuberculosis
• Significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• History of prior malignancy within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year overall survival [OS] of > 90%), such as but not limited to, non-melanoma skin carcinoma, ductal carcinoma in situ, or stage I endometriod uterine cancer, and others at the discretion of the principal investigator (PI)
• 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
• Prior allogeneic stem cell or solid organ transplantation
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti−CTLA-4, anti−PD-1, and anti−PD-L1 therapeutic antibodies
• A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study initiation; corticosteroids with minimal systemic absorption (inhaled or topical steroids) are permitted
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
• Known allergy or hypersensitivity to any component of the atezolizumab formulation
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the last dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment