Testing Atezolizumab in People 2-17 Years Old With Clear Cell Sarcoma or Advanced Chondrosarcoma

NCT04458922 | Active Not Recruiting Phase 2 Results FDA Drug

• 4 other identifiers: NCI-2020-0463400008120-C-XXXX10398
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 15

Brief Summary

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.

Conditions

Central Chondrosarcoma, Grade 2; Central Chondrosarcoma, Grade 3; Dedifferentiated Chondrosarcoma; Metastatic Clear Cell Sarcoma of Soft Tissue; Metastatic Primary Central Chondrosarcoma; Unresectable Primary Central Chondrosarcoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rates (ORR)

  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.

Secondary Outcomes (3)

• Duration of Response (DOR) or Change in Clinical Symptoms

  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

• Progression-free Survival (PFS) Time

  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

• Number of Activated Cluster of Differentiation 8 (CD8+) T Cells Infiltrating the Tumor

  Up to 3 years on Cycle 1 Day 1 and Cycle 3 Day 1

Other Outcomes (1)

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

  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.

Study Arms (1)

Treatment (atezolizumab)

EXPERIMENTAL

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

Drug: Atezolizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Treatment (atezolizumab)

Biopsy Procedure PROCEDURE

Correlative studies

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (atezolizumab)

Biospecimen Collection PROCEDURE

Correlative studies

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (atezolizumab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (atezolizumab)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \>= 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:

You may not qualify if:

• 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-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 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (15)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

NCI - Center for Cancer Research

Bethesda, Maryland, 20892, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Sarcoma, Clear Cell

Interventions

atezolizumab; Biopsy; Specimen Handling

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Alice P. Chen
• Organization: National Cancer Institute

chenali@mail.nih.gov

240-781-3274

Study Officials

• A P Chen

  National Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2020
• First Posted: July 7, 2020
• Study Start: October 5, 2020
• Primary Completion: November 28, 2022
• Study Completion (Estimated): December 17, 2026
• Last Updated: April 13, 2026
• Results First Posted: October 23, 2023

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); US (14)