NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

A Phase 2 Study of Anti-PD-L1 Antibody (Atezolizumab) in Chondrosarcoma and Clear Cell Sarcoma

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 2
Max Age: N/A

Referral Letter Required


Population Exclusion(s)



Immune Checkpoint Inhibitor;

Recruitment Keyword(s)



Clear Cell Sarcoma;

Investigational Drug(s)


Investigational Device(s)



Drug: Atezolizumab

Supporting Site

National Cancer Institute


Clear cell sarcoma (CCS) is a rare, aggressive tumor. Chondrosarcoma (CS) is one of the most common malignant bone tumors in adults. People with these types of advanced cancers usually don t have effective treatment options. Researchers want to see if a drug can help.


To test the good and bad effects of atezolizumab and to see if it causes cancer to shrink by at least one-quarter compared to its present size.


People age 2 and older with advanced CCS or CS that is not curable by surgery and for which there is no standard treatment.


Participants will be screened with a medical history and physical exam. They will have an assessment of how they are doing with their daily living activities. They will have heart tests. They will give blood samples. They will have imaging scans to measure their tumor. This may include computed tomography scans or other imaging tests such as ultrasound, magnetic resonance imaging, or positron emission tomography.

Screening tests will be repeated during the study.

Participants will get atezolizumab through a vein in the arm once every 3 weeks (21 days). They will be monitored for side effects. They will take the study drug until their tumor grows or they have serious side effects.

Adult participants will have tumor biopsies.

Participants blood and tumor samples will be used for protein and gene testing.

After they stop taking the study drug, participants will be followed for 30 days from their last treatment date or until a new treatment is started. They will have a telephone call from the Study Team.

--Back to Top--



-Patients must have documented EWSR1/ATF1 or EWSR1/CREB1 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 greater than or equal to 20 mm (greater than or equal to 2 cm) by chest x-ray or as

greater than or equal to 10 mm (greater than or equal to 1 cm) with CT scan, 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 greater than or equal to 2 years at the NCI Clinical Center (greater than or equal to 12 years at other participating sites)

-ECOG performance status less than or equal to 2 (Karnofsky or Lansky greater than or equal to 70%).

-Life expectancy of greater than 3 months.

-Patients must have adequate organ and marrow function as defined below:

--absolute neutrophil count greater than or equal to 1,000/mcL

--platelets greater than or equal to 100,000/mcL

--hemoglobin greater than or equal to 8 g/dL

--total bilirubin less than or equal to institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level less than or equal to 3 ULN may be enrolled)

--AST(SGOT)/ALT(SGPT) less than or equal to 3 (SqrRoot) institutional ULN (AST and/or ALT less than or equal to 5 ULN for patients with liver involvement)

--alkaline phosphatase less than or equal to 2.5 (SqrRoot) ULN (less than or equal to 5 ULN for patients with documented liver involvement or bone metastases)

--creatinine For adult patients (greater than or equal to 18 years of age): greater than or equal to 30 mL/min/1.73 m^2 by Cockroft-Gault

(140 - age) x (weight in kg)/72 x (serum creatinine in mg/dL) (x 0.85 if female)

For pediatric patients (<18 years of age), a serum creatinine based on age and gender as follows:

-Serum Creatinine for Age/Gender:

--Age 2 to <6 years; Male 0.8; Female 0.8

--Age 6 to <10 years; Male 1; Female 1

--Age 10 to <13 years; Male 1.2; Female 1.2

--Age 13 to <16 years; Male 1.5; Female 1.4

--Age 16 to <18 years Male 1.7; Female 1.4

-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 greater than or equal to 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 greater than or equal to 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.


-Any prior therapy must have been completed greater than or equal to 4 weeks or, if known, greater than or equal to 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 greater than or equal to 4 weeks or palliative radiation should have been completed greater than or equal to 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 PI s discretion). Patients who have had prior monoclonal antibody therapy must have completed that therapy greater than or equal to 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 enrolled if their ejection fraction measured by an echocardiogram is within normal institutional limits.

-Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents.

--Patients who have received prior treatment with anti-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 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 greater than or equal to 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 HIV-positive on antiretroviral therapy are eligible with an undetectable viral load. For these 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. For these patients, HBsAg and anti-HBc tests must be done within 28 days prior to enrollment.

--Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. For these patients, an HCV RNA test must be done within 28 days prior to enrollment.

-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, Sj(SqrRoot)(Delta)gren s syndrome, Bell s palsy, Guillain-Barr(SqrRoot)(Copyright) 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 that 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%, flucinolone 0.01%, desonide 0.05%, aclometasone 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.

--Back to Top--


Thanindratarn P, Dean DC, Nelson SD, Hornicek FJ, Duan Z. Advances in immune checkpoint inhibitors for bone sarcoma therapy. J Bone Oncol. 2019 Jan 29;15:100221. doi: 10.1016/j.jbo.2019.100221. PMID: 30775238; PMCID: PMC6365405.

Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014 Nov 27;515(7528):563-7. doi: 10.1038/nature14011. PMID: 25428504; PMCID: PMC4836193.

--Back to Top--


Principal Investigator

Referral Contact

For more information:

Alice P. Chen, M.D.
National Cancer Institute (NCI)
(240) 781-3320

Nancy Moore, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 8D53
10 Center Drive
Bethesda, Maryland 20892
(240) 760-6045

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


--Back to Top--