Clinical Trials /

Atezolizumab in Treating Patients With Newly Diagnosed and Metastatic Alveolar Soft Part Sarcoma That Cannot Be Removed by Surgery

NCT03141684

Description:

This phase II trial studies how well atezolizumab works in treating patients with alveolar soft part sarcoma that has not been treated, has spread from where it started to other places in the body and cannot be removed by surgery. 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.

Related Conditions:
  • Alveolar Soft Part Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Atezolizumab in Treating Patients With Newly Diagnosed and Metastatic Alveolar Soft Part Sarcoma That Cannot Be Removed by Surgery
  • Official Title: A Phase 2 Study of Anti-PD-L1 Antibody (Atezolizumab) in Alveolar Soft Part Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: NCI-2016-01040
  • SECONDARY ID: NCI-2016-01040
  • SECONDARY ID: 17-C-007
  • SECONDARY ID: CC 17-C-0074
  • SECONDARY ID: 10005
  • SECONDARY ID: 10005
  • SECONDARY ID: ZIABC011078
  • NCT ID: NCT03141684
  • NCT ALIAS: NCT03233698

Conditions

  • Metastatic Alveolar Soft Part Sarcoma

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqTreatment (atezolizumab)

Purpose

This phase II trial studies how well atezolizumab works in treating patients with alveolar soft part sarcoma that has not been treated, has spread from where it started to other places in the body and cannot be removed by surgery. Monoclonal antibodies, such as atezolizumab, may allow the immune system cells to find and kill the tumor cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Determine the objective response rate (ORR) using Response Evaluation Criteria in Solid
      Tumors (RECIST) version (v) 1.1 of atezolizumab in patients with advanced alveolar soft part
      sarcoma (ASPS) in adult subjects >= 18 years and in pediatric/adolescent subjects >= 6 years.

      SECONDARY OBJECTIVES:

      I. Determine duration of response (DOR) using RECIST v 1.1 and/or change in clinical
      symptoms.

      II. Measure progression-free survival (PFS) time as determined by investigator using RECIST v
      1.1.

      III. Correlate response with expression of potential immune biomarkers in paired biopsies.

      IV. Compare RECIST v 1.1 versus (vs) immune RECIST (iRECIST) in patients with ASPS on
      atezolizumab.

      OUTLINE:

      Patients receive atezolizumab intravenously (IV) over 60 minutes on day 1. Courses repeat
      every 21 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 27-30 days.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (atezolizumab)ExperimentalPatients receive atezolizumab IV over 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed alveolar soft part
             sarcoma that is not curable by surgery; diagnosis of malignancy must be confirmed by
             the department of pathology at the institution where the patient is enrolled prior to
             patient enrollment

          -  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 ASPS 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 >= 6 years at the NCI clinical center (>= 18 years at other participating sites)

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 70%)

          -  Life expectancy of greater than 3 months

          -  Leukocytes >= 2,500/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >= 8 g/dL

          -  Total bilirubin =< 1.5 x 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 glutamic pyruvic transaminase [SGPT]) =<
             3 x 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 clearance >= 30 mL/min/1.73 m^2 by Cockcroft-Gault

          -  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

          -  Willingness to provide biopsy samples for research purposes (patients >= 18 years of
             age at the National Cancer Institute [NCI] Clinical Center only)

        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);
             patients who have received more than a cumulative dose of 350 mg/m^2 of doxorubicin
             may be enrolled at the discretion of the coordinating center PI, with a screening
             echocardiogram

          -  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, 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

          -  Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS
             metastases are excluded, with the following exceptions:

               -  Patients with asymptomatic untreated CNS disease may be enrolled, provided all of
                  the following criteria are met:

                    -  Evaluable or measurable disease outside the CNS

                    -  No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within
                       10 mm of the optic apparatus (optic nerves and chiasm)

                    -  No history of intracranial hemorrhage or spinal cord hemorrhage

                    -  No ongoing requirement for dexamethasone for CNS disease; patients on a
                       stable dose of anticonvulsants are permitted

                    -  No neurosurgical resection or brain biopsy within 28 days prior to cycle 1,
                       day 1

               -  Patients with asymptomatic treated CNS metastases may be enrolled, provided all
                  the criteria listed above are met as well as the following:

                    -  Radiographic demonstration of improvement upon the completion of
                       CNS-directed therapy and no evidence of interim progression between the
                       completion of CNS-directed therapy and radiographic screening for the
                       current study

                    -  No stereotactic radiation or whole-brain radiation within 28 days prior to
                       cycle 1, day 1

                    -  Screening CNS radiographic study >= 4 weeks from completion of radiotherapy
                       and >= 2 weeks from discontinuation of corticosteroids

          -  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; breastfeeding should be discontinued if
             the mother is treated with atezolizumab

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible; patients must also have a CD4 count > 350 cells/mm^3 with an
             undetectable viral load

          -  Patients on supraphysiologic doses of steroids or use of such within the previous six
             weeks

          -  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 controlled type 1 diabetes mellitus on a stable insulin regimen may
                  be eligible • Patients with eczema, psoriasis, lichen simplex chronicus of
                  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%,
                       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 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

          -  Patients requiring treatment with a RANKL inhibitor (e.g. denosumab) who cannot
             discontinue it before treatment with atezolizumab
      
Maximum Eligible Age:N/A
Minimum Eligible Age:6 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate evaluated using Response Evaluation Criteria in Solid Tumors version 1.1
Time Frame:Up to 4 weeks after the last dose of study treatment
Safety Issue:
Description:If at least 3 responses (at least 12.5%) are observed among the 24 evaluable patients, this regimen would be considered worthy of further testing in this disease.

Secondary Outcome Measures

Measure:Duration of response using Response Evaluation Criteria in Solid Tumors version 1.1
Time Frame:Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study, assessed up to 4 weeks after the last dose of study treatment
Safety Issue:
Description:Exploratory evaluations will be performed, with results reported with appropriate caveats about the exploratory nature of the analysis, and without formal adjustment for multiple comparisons.
Measure:Progression free survival evaluated using Response Evaluation Criteria in Solid Tumors version 1.1
Time Frame:Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study, assessed up to 4 weeks after the last dose of study treatment
Safety Issue:
Description:Exploratory evaluations will be performed, with results reported with appropriate caveats about the exploratory nature of the analysis, and without formal adjustment for multiple comparisons.
Measure:Immune biomarkers in paired biopsies
Time Frame:Up to 4 weeks after the last dose of study treatment
Safety Issue:
Description:Response will be correlated with expression of potential immune biomarkers in paired biopsies. Exploratory evaluations will be performed, with results reported with appropriate caveats about the exploratory nature of the analysis, and without formal adjustment for multiple comparisons.
Measure:Immune-related response evaluated by immune Response Evaluation Criteria in Solid Tumors
Time Frame:Up to 4 weeks after the last dose of study treatment
Safety Issue:
Description:Response evaluated with immune Response Evaluation Criteria in Solid Tumors version 1.1 will be compared to immune Response Evaluation Criteria in Solid Tumors. Exploratory evaluations will be performed, with results reported with appropriate caveats about the exploratory nature of the analysis, and without formal adjustment for multiple comparisons.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

March 2, 2018