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Testing Atezolizumab With or Without Selinexor in Patients >= 18 Years Old With Alveolar Soft Part Sarcoma, the Axiom Study

Primary Purpose

Advanced Alveolar Soft Part Sarcoma, Advanced Soft Tissue Sarcoma, Metastatic Alveolar Soft Part Sarcoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Atezolizumab
Biopsy
Biospecimen Collection
Computed Tomography
Magnetic Resonance Imaging
Selinexor
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Alveolar Soft Part Sarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • To be enrolled in the safety run-in, patients must have an advanced soft tissue sarcoma (not otherwise specified [NOS]). To be enrolled in the randomized arms, patients must have histologically or cytologically confirmed alveolar soft part sarcoma that is not 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 CT scan, MRI, or calipers by clinical exam
  • Patients with unresectable, metastatic and measurable ASPS will be eligible for the randomized portion of this study 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 >= 18 years. Because no dosing or adverse event data are currently available on the use of atezolizumab in combination with selinexor in patients ˂ 18 years of age, children are excluded from this study
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 70%)
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9 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]) =< 2.5 x institutional ULN or =< 5 x ULN for patients with liver metastases
  • Serum creatinine =< 1.5 x institutional ULN OR creatinine clearance >= 30 mL/min/1.73 m^2 by Cockcroft-Gault
  • International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-weight heparin or warfarin, should be on a stable dose.)
  • Serum albumin >= 2.5 g/dL
  • Baseline sodium (Na+) >= 130 mEq/L
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 28 days are eligible for this trial
  • Administration of selinexor or 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, for 90 days after the last dose of selinexor, and for 150 days after the last dose of atezolizumab, whichever is longer. Breastfeeding is not allowed while on selinexor or for 90 days after the last dose of selinexor. 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
  • Willingness to provide biopsy samples for research purposes, except patients enrolled on the safety run-in
  • Ability and willingness to swallow pills
  • Vaccines intended to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) are allowed

Exclusion Criteria:

  • Malabsorption syndrome or other conditions that would interfere with intestinal absorption
  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. However, the following therapies are allowed:

    • Hormone-replacement therapy or oral contraceptives
    • Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as anti-cancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)
    • Palliative radiotherapy for bone metastases > 2 weeks prior to cycle 1, day 1
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-1, anti-PD-1, or anti-PD-L1 therapeutic antibodies, for patients in the randomized arms; these prior therapies are allowed for patients in the safety run-in
  • Treatment with any other agent administered for the treatment of the patient's cancer, within four half-lives or 4 weeks prior to cycle 1, day 1, whichever is shorter
  • History of malignancy other than ASPS prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival [OS] rate > 90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
  • 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 or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:

    • Patients who have received acute, low dose, systemic immunosuppressant medications or one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible after Principal Investigator confirmation has been obtained
    • Patients who have received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenocortical insufficiency are eligible
  • 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, or cerebellum
      • No history of intracranial hemorrhage or spinal cord hemorrhage
      • No ongoing requirement for dexamethasone for CNS; 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
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric antibodies, fusion proteins, or Chinese hamster ovary cell products or to any component of the atezolizumab formulation
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to atezolizumab or selinexor
  • Patients with uncontrolled intercurrent illness, prior malignancy, 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
  • Patients who are pregnant or breastfeeding, or are expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 5 months after the last dose of atezolizumab or 3 months after the last dose of selinexor, whichever is longer. A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test (e.g., within 8 days) prior to treatment will be excluded from the study. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Women of childbearing potential must have a negative urine pregnancy test result within 8 days prior to initiation of study treatment. Pregnant women are excluded from this study because atezolizumab is a monoclonal antibody agent with the 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. These potential risks may also apply to selinexor. Due to the potential risks, WOCBPs and men 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 5 months after completion of atezolizumab administration or 3 months after completion of selinexor administration, whichever is longer. 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
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • 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 ribonucleic acid (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, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions:

    • Patients with a history of autoimmune-related 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, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided all of the following conditions are met:

      • Rash must cover less than 10% of body surface area (BSA)
      • Disease is well controlled at baseline and only requiring low potency topical steroids
      • 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) within the previous 12 months
  • 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 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 are ineligible
  • 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 IIB or better
  • Patients with active tuberculosis (TB) are excluded
  • Patients with mild or moderate signs or symptoms of infection within 2 weeks prior to cycle 1, day 1 (including, but not limited to, receiving oral or intravenous [IV] antibiotics) are excluded. Patients with 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) are excluded. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
  • Patients with 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) are excluded.
  • Major surgical procedure within 28 days prior to cycle 1, day 1
  • 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
  • History of leptomeningeal disease
  • Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry, with no changes to their pain regimen in the 4 weeks prior to enrollment
  • Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period
  • Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
  • Patients with indwelling catheters (e.g., PleurX) are allowed
  • Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)
  • 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
  • Current treatment with anti-viral therapy for HBV
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment

Sites / Locations

  • Keck Medicine of USC KoreatownRecruiting
  • Los Angeles County-USC Medical CenterRecruiting
  • USC / Norris Comprehensive Cancer CenterRecruiting
  • National Cancer Institute Developmental Therapeutics ClinicRecruiting
  • National Institutes of Health Clinical CenterRecruiting
  • University of Oklahoma Health Sciences CenterRecruiting
  • University of Pittsburgh Cancer Institute (UPCI)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (atezolizumab, selienexor)

Arm II (atezolizumab)

Arm Description

Patients receive atezolizumab IV over 30-60 minutes on day 8 of cycle 1, and then on day 1 of subsequent cycles. Patients also receive selinexor PO QW on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy at baseline, cycle 1 day 8 and cycle 3 day 1, CT and MRI at baseline, end of cycle 2, and every 2 cycles thereafter, and collection of blood samples throughout the study.

Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Patients also undergo biopsy at baseline and cycle 3 day 1, CT and MRI at baseline, end of cycle 2, and every 2 cycles thereafter, and collection of blood samples throughout the study.

Outcomes

Primary Outcome Measures

Objective response rate
Defined by Response Evaluation Criteria in Solid Tumors version 1.1, and calculated using a two-sample test of proportions (normal approximation) with one-sided type-I error 0.1.

Secondary Outcome Measures

Progressive disease (PD)
Defined as minimum of 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) AND an absolute increase of >= 5 mm. Appearance of new lesions will also constitute PD (including lesions in previously unassessed areas).

Full Information

First Posted
April 15, 2022
Last Updated
September 26, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05333458
Brief Title
Testing Atezolizumab With or Without Selinexor in Patients >= 18 Years Old With Alveolar Soft Part Sarcoma, the Axiom Study
Official Title
A Randomized Phase 2 Study of Atezolizumab With or Without Selinexor in Alveolar Soft Part Sarcoma (AXIOM)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 29, 2022 (Actual)
Primary Completion Date
May 1, 2025 (Anticipated)
Study Completion Date
May 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase II trial tests whether atezolizumab alone or in combination with selinexor works to shrink tumors in patients with alveolar soft part sarcoma and whether the study drugs are better than the usual approach in treating this type of cancer. The usual approach is defined as care most people get for alveolar soft part sarcoma if they are not part of a clinical study, which includes treatment with radiation, kinase inhibitor drugs, immunotherapy drugs, or chemotherapy drugs. 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. Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by blocking a protein called CRM1, which may help keep cancer cells from growing and may kill them. Giving atezolizumab alone or in combination with selinexor may help shrink tumors and stabilize the cancer in patients with alveolar soft part sarcoma.
Detailed Description
PRIMARY OBJECTIVE: I. Determine the overall response rate (by Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1) for selinexor in combination with atezolizumab in immune checkpoint inhibitor (ICI)-naive patients with alveolar soft part sarcoma (ASPS). SECONDARY OBJECTIVE: I. Assess the number of activated CD8+ T cells infiltrating the tumor before and after atezolizumab + selinexor combination treatment, and correlate treatment-induced changes with clinical response. EXPLORATORY OBJECTIVES: I. Compare RECIST v 1.1 versus (vs) immune RECIST (iRECIST) in patients with ASPS on atezolizumab + selinexor. II. Examine changes in PD-1/PD-L1 expression in the tumor microenvironment before and after atezolizumab + selinexor treatment, and correlate treatment-induced changes with clinical response. III. Evaluate potential associations between atezolizumab + selinexor activity and tumor genomic alterations. OUTLINE: This is a randomized phase 2 trial that incorporates a safety run-in of the selinexor in combination with atexolizumab. After the safety run-in phase, patients are randomized to 1 of 2 arms. Patients with advanced soft tissue sarcoma are assigned to Arm I. ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 8 of cycle 1, and then on day 1 of subsequent cycles. Patients also receive selinexor orally (PO) once weekly (QW) on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy at baseline, cycle 1 day 8 and cycle 3 day 1, computed tomography (CT) and magnetic resonance imaging (MRI) at baseline, end of cycle 2, and every 2 cycles thereafter, and collection of blood samples throughout the study. ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Patients also undergo biopsy at baseline and cycle 3 day 1, CT and MRI at baseline, end of cycle 2, and every 2 cycles thereafter, and collection of blood samples throughout the study. After completion of study treatment, participants are followed up for 30 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Alveolar Soft Part Sarcoma, Advanced Soft Tissue Sarcoma, Metastatic Alveolar Soft Part Sarcoma, Unresectable Alveolar Soft Part Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
77 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (atezolizumab, selienexor)
Arm Type
Experimental
Arm Description
Patients receive atezolizumab IV over 30-60 minutes on day 8 of cycle 1, and then on day 1 of subsequent cycles. Patients also receive selinexor PO QW on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy at baseline, cycle 1 day 8 and cycle 3 day 1, CT and MRI at baseline, end of cycle 2, and every 2 cycles thereafter, and collection of blood samples throughout the study.
Arm Title
Arm II (atezolizumab)
Arm Type
Experimental
Arm Description
Patients receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Patients also undergo biopsy at baseline and cycle 3 day 1, CT and MRI at baseline, end of cycle 2, and every 2 cycles thereafter, and collection of blood samples throughout the study.
Intervention Type
Biological
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
BIOPSY_TYPE, Bx
Intervention Description
Undergo biopsy
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo collection of blood samples
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
Intervention Description
Undergo CT
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
Intervention Description
Undergo MRI
Intervention Type
Drug
Intervention Name(s)
Selinexor
Other Intervention Name(s)
ATG-010, CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Nexpovio, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330, Xpovio
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Objective response rate
Description
Defined by Response Evaluation Criteria in Solid Tumors version 1.1, and calculated using a two-sample test of proportions (normal approximation) with one-sided type-I error 0.1.
Time Frame
Upon observation and confirmed 4-8 weeks later
Secondary Outcome Measure Information:
Title
Progressive disease (PD)
Description
Defined as minimum of 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) AND an absolute increase of >= 5 mm. Appearance of new lesions will also constitute PD (including lesions in previously unassessed areas).
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: To be enrolled in the safety run-in, patients must have an advanced soft tissue sarcoma (not otherwise specified [NOS]). To be enrolled in the randomized arms, patients must have histologically or cytologically confirmed alveolar soft part sarcoma that is not 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 CT scan, MRI, or calipers by clinical exam Patients with unresectable, metastatic and measurable ASPS will be eligible for the randomized portion of this study 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 >= 18 years. Because no dosing or adverse event data are currently available on the use of atezolizumab in combination with selinexor in patients ˂ 18 years of age, children are excluded from this study Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 70%) Absolute neutrophil count >= 1,500/mcL Platelets >= 100,000/mcL Hemoglobin >= 9 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]) =< 2.5 x institutional ULN or =< 5 x ULN for patients with liver metastases Serum creatinine =< 1.5 x institutional ULN OR creatinine clearance >= 30 mL/min/1.73 m^2 by Cockcroft-Gault Serum albumin >= 2.5 g/dL Baseline sodium (Na+) >= 130 mEq/L Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 28 days are eligible for this trial Administration of selinexor or 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, for 90 days after the last dose of selinexor, and for 150 days after the last dose of atezolizumab, whichever is longer. Breastfeeding is not allowed while on selinexor or for 90 days after the last dose of selinexor. 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 Willingness to provide biopsy samples for research purposes, except patients enrolled on the safety run-in. Patients that cannot be safely biopsied may be considered for the randomized part of the study upon discussion with principal investigator Ability and willingness to swallow pills Vaccines intended to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) are allowed Exclusion Criteria: Malabsorption syndrome or other conditions that would interfere with intestinal absorption Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. However, the following therapies are allowed: Hormone-replacement therapy or oral contraceptives Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as anti-cancer therapy must be discontinued at least 1 week prior to cycle 1, day 1) Palliative radiotherapy for bone metastases > 2 weeks prior to cycle 1, day 1 Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-1, anti-PD-1, or anti-PD-L1 therapeutic antibodies, for patients in the randomized arms; these prior therapies are allowed for patients in the safety run-in Treatment with any other agent administered for the treatment of the patient's cancer, within five half-lives or 4 weeks prior to cycle 1, day 1, whichever is shorter History of malignancy other than ASPS prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival [OS] rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment 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 or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: Patients who have received acute, low dose, systemic immunosuppressant medications or one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible after Principal Investigator confirmation has been obtained Patients who have received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenocortical insufficiency are eligible 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, or cerebellum No history of intracranial hemorrhage or spinal cord hemorrhage No ongoing requirement for dexamethasone for CNS; 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 History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric antibodies, fusion proteins, or Chinese hamster ovary cell products or to any component of the atezolizumab formulation History of allergic reactions attributed to compounds of similar chemical or biologic composition to atezolizumab or selinexor Patients with uncontrolled intercurrent illness, prior malignancy, 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 Patients who are pregnant or breastfeeding, or are expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 5 months after the last dose of atezolizumab or 3 months after the last dose of selinexor, whichever is longer. A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test (e.g., within 8 days) prior to treatment will be excluded from the study. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Women of childbearing potential must have a negative urine pregnancy test result within 8 days prior to initiation of study treatment. Pregnant women are excluded from this study because atezolizumab is a monoclonal antibody agent with the 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. These potential risks may also apply to selinexor. Due to the potential risks, WOCBPs and men 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 5 months after completion of atezolizumab administration or 3 months after completion of selinexor administration, whichever is longer. 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 Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation 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 ribonucleic acid (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, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions: Patients with a history of autoimmune-related 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, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided all of the following conditions are met: Rash must cover less than 10% of body surface area (BSA) Disease is well controlled at baseline and only requiring low potency topical steroids 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) within the previous 12 months 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 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 are ineligible 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 IIB or better Patients with active tuberculosis (TB) are excluded Patients with mild or moderate signs or symptoms of infection within 2 weeks prior to cycle 1, day 1 (including, but not limited to, receiving oral or intravenous [IV] antibiotics) are excluded. Patients with 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) are excluded. 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 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 History of leptomeningeal disease Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry, with no changes to their pain regimen in the 4 weeks prior to enrollment Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX [registered trademark]) are allowed Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN) 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 Current treatment with anti-viral therapy for HBV Treatment with investigational therapy within five half-lives or 28 days prior to initiation of study treatment, whichever is shorter
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alice P Chen
Organizational Affiliation
National Cancer Institute LAO
Official's Role
Principal Investigator
Facility Information:
Facility Name
Keck Medicine of USC Koreatown
City
Los Angeles
State/Province
California
ZIP/Postal Code
90020
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
213-388-0908
First Name & Middle Initial & Last Name & Degree
James S. Hu
Facility Name
Los Angeles County-USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
323-865-0451
First Name & Middle Initial & Last Name & Degree
James S. Hu
Facility Name
USC / Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
323-865-0451
First Name & Middle Initial & Last Name & Degree
James S. Hu
Facility Name
National Cancer Institute Developmental Therapeutics Clinic
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
800-411-1222
First Name & Middle Initial & Last Name & Degree
Geraldine O'Sullivan Coyne
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
800-411-1222
First Name & Middle Initial & Last Name & Degree
Geraldine O'Sullivan Coyne
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
405-271-8777
Email
ou-clinical-trials@ouhsc.edu
First Name & Middle Initial & Last Name & Degree
Minh Phan
Facility Name
University of Pittsburgh Cancer Institute (UPCI)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
412-647-8073
First Name & Middle Initial & Last Name & Degree
Melissa A. Burgess

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
IPD Sharing URL
https://grants.nih.gov/policy/sharing.htm

Learn more about this trial

Testing Atezolizumab With or Without Selinexor in Patients >= 18 Years Old With Alveolar Soft Part Sarcoma, the Axiom Study

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