Testing Atezolizumab in People With Clear Cell Sarcoma or Advanced Chondrosarcoma

This phase II trial studies how well atezolizumab works in treating patients with chondrosarcoma or clear cell sarcoma that is newly diagnosed, cannot be removed by surgery (unresectable), or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVE: I. Determine the objective response rates (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 of atezolizumab in adult (>= 18 years) patients with clear cell sarcoma (CCS) and chondrosarcoma (CS). SECONDARY OBJECTIVES: I. Determine duration of response (DOR) using RECIST v 1.1 and/or change in clinical symptoms (time frame: baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination). II. Measure progression-free survival (PFS) time (time frame: baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination). III. Assess the number of activated cluster of differentiation 8 (CD8+) T cells infiltrating the tumor before and after atezolizumab treatment, and correlate treatment-induced changes with clinical response. EXPLORATORY OBJECTIVES: I. Compare RECIST v 1.1 versus (vs) immune RECIST Response Evaluation Criteria in Solid Tumors (RECIST) in patients with clear cell sarcoma (CCS) and CS on atezolizumab. II. Examine changes in programmed death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) expression in the tumor microenvironment before and after atezolizumab treatment, and correlate treatment-induced changes with clinical response. III. Evaluate potential associations between atezolizumab activity and tumor genomic alterations. OUTLINE: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scans and undergo biopsy and collection of blood samples on study. After completion of study treatment, patients are followed up to 90 days.

Conventional Chondrosarcoma, Grade 2, Conventional Chondrosarcoma, Grade 3, Dedifferentiated Chondrosarcoma, Metastatic Clear Cell Sarcoma, Metastatic Primary Conventional Chondrosarcoma, Unresectable Primary Conventional Chondrosarcoma

Patients receive atezolizumab intravenous (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scans and undergo biopsy and collection of blood samples on study.

CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

ORR was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, which involves the following response definitions. Complete Response (CR): disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive Disease (PD): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

Baseline until confirmation of progressive disease or response (complete or partial) as defined by RECIST v1.1, an average of 4 months.

Duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Complete Response (CR): disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progression was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 and/or change in clinical symptoms. Progressive Disease (PD): is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination, assessed up to 3 years

PFS is the time interval from start of treatment to documented evidence of disease progression, measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, or death from any cause, whichever comes first. Progressive Disease (PD): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination, assessed up to 3 years

Activated CD8+ T cells will be detected by multiplex immunofluorescence assays and will be defined by the expression of T cell receptor (TCR) activation (Zeta chain phosphorylation) or phosphorylated Zap70 (pY493); CD8+ cells present within the tumor section that are positive for these markers will be quantified.

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Date treatment consent signed to date off study, approximately 11 months and 22 days, 8 months and 27 days, and 11 months and 22 days for each Arm/Group respectively.

Inclusion Criteria: Patients must have documented EWS ribonucleic acid protein binding 1 (EWSR1) /Activating Transcription Factor 1 (ATF1) or EWSR1/CAMP-response element binding protein (CREB) translocation or histologically confirmed clear cell sarcoma, documented grade 2 or 3 conventional chondrosarcoma, or documented dedifferentiated chondrosarcoma. The disease must not be curable by surgery. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam Patients with newly diagnosed, unresectable, metastatic and measurable clear cell sarcoma, EWSR1/ATF1 or EWSR1/CREB1 translocation, grade 2 or 3 conventional chondrosarcoma, or dedifferentiated chondrosarcoma will also be eligible if they show clinical evidence of disease progression (including history and increasing physical symptoms). On-study documentation will include a physician's rationale that supports evidence of clinical disease progression (i.e., increasing tumor pain) Age >= 2 years at the National Cancer Institute (NCI) Clinical Center (>= 12 years at other participating sites) Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky or Lansky >= 70%) Life expectancy of greater than 3 months Absolute neutrophil count >= 1,000/mcL Platelets >= 100,000/mcL Hemoglobin >= 8 g/dL Total bilirubin =< institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled) Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN (AST and/or ALT =< 5 x ULN for patients with liver involvement) Alkaline phosphatase =< 2.5 x ULN (=< 5 x ULN for patients with documented liver involvement or bone metastases) Creatinine: For adult patients (>= 18 years of age): >= 30 mL/min/1.73 m^2 by Cockcroft-Gault For pediatric patients (< 18 years of age), a serum creatinine based on age and gender as follows: Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) 0.8 (female) Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male) 1 (female) Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) 1.2 (female) Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) 1.4 (female) Age: 16 to < 18 years; Maximum serum creatinine (mg/dL): 1.7 (male) 1.4 (female) Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for >= 1 month after treatment of the brain metastases Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS-specific treatment is not required and is unlikely to be required during the first 2 cycles of therapy Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. Willingness to provide biopsy samples for research purposes (patients >= 18 years of age only) Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Female patients of child-bearing potential and male patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign a written informed consent document or a parent/guardian able to do the same Exclusion Criteria: Any prior therapy must have been completed >= 4 weeks or, if known, >= 5 half-lives of the prior agent (whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment), and the participant must have recovered to eligibility levels from prior toxicity. Patients should be at least 6 weeks out from nitrosoureas and mitomycin C. Prior definitive radiation should have been completed >= 4 weeks or palliative radiation should have been completed >= 2 weeks prior to study enrollment and all associated toxicities resolved to eligibility levels (patients on study may be eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy at the principal investigator [PI's] discretion). Patients who have had prior monoclonal antibody therapy must have completed that therapy >= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment). A patient who has received a cumulative dose of > 350 mg/m^2 of anthracycline (regardless of cardioprotectant) may only be enrolled if their ejection fraction measured by an echocardiogram is within normal institutional limits. Prior treatment with anti-programmed death 1 (PD-1), or anti-programmed cell death 1 ligand 1 (PD-L1) therapeutic antibody or pathway-targeting agents Patients who have received prior treatment with anti-cluster of differentiation 152 (CTLA-4) may be enrolled, provided the following requirements are met: Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose No history of severe immune-related adverse effects from anti-CTLA-4 (NCI Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4) Treatment with any other investigational agent within 4 weeks (or within five half-lives of the investigational product, whichever is shorter) prior to cycle 1, day 1 (minimum of 1 week between prior therapy and study enrollment). Patients must be >= 2 weeks since any investigational agent administered as part of a phase 0 study (also referred to as an "early phase I study" or "pre-phase I study" where a sub-therapeutic dose of drug is administered) at the coordinating center PI's discretion, and should have recovered to eligibility levels from any toxicities Treatment with systemic immunostimulatory agents (including, but not limited to, interferon-alpha or interleukin-2 [aldesleukin]) within 6 weeks prior to cycle 1, day 1 Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone [ > 10 mg/day], cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to cycle 1, day 1. Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled. The use of inhaled corticosteroids and systemic mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed. Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies (i.e., antibodies with generic names ending in "ximab" or "zumab", respectively) or fusion proteins Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because atezolizumab is an investigational agent with the unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding should be discontinued if the mother is treated with atezolizumab. Patients with a history of human immunodeficiency virus (HIV)-positive on antiretroviral therapy are eligible with an undetectable viral load. For those patients, an HIV viral load test must be completed within 28 days prior to enrollment. 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-HBc [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 (PCR) is negative for HCV ribonucleic acid (RNA) History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible Patients with autoimmune hyperthyroid disease not requiring immunosuppressive treatment may be eligible Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided they meet the following conditions: Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations Rash must cover less than 10% of body surface area (BSA) Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids) History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. Patients with active tuberculosis (TB) are excluded Severe infections within 4 weeks prior to cycle 1, day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia Signs or symptoms of infection within 2 weeks prior to cycle 1, day 1 Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible. Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of need for a major surgical procedure, during the course of the study Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior to cycle 1, day 1 or at any time during the study.

National Cancer Institute (NCI) is committed to sharing data in accordance with National Institutes of Health (NIH) policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Clinical data will be made available via subscription to the Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).