Neoplasms

All Conditions

Rare Diseases

Sarcoma

Sarcoma, Alveolar Soft Part

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Alveolar Soft Part Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

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.

Biopsy

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Selinexor

Site Public Contact

James S. Hu

Sosipatros A. Boikos

A P. Chen

Minh Phan

Melissa A. Burgess

Anthony P. Conley

Alice P Chen

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.

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.

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

A Randomized Phase 2 Study of Atezolizumab With or Without Selinexor in Alveolar Soft Part Sarcoma (AXIOM)

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.

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.

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).

National Cancer Institute (NCI)

Bevacizumab

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT imaging, and collection of blood and urine at baseline.

Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT imaging, and collection of blood and urine at baseline.

This phase II trial studies how well atezolizumab or atezolizumab plus bevacizumab 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 (advanced) and cannot be removed by surgery (unresectable). Atezolizumab works by unblocking the immune system, allowing the immune system cells to recognize and then attack tumor cells. Bevacizumab works by controlling the growth of new blood vessels. Giving atezolizumab alone or atezolizumab with bevacizumab may shrink the cancer.

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 \>= 2 years.

II. Determine the ORR using RECIST v 1.1 of atezolizumab and bevacizumab in subjects \>= 18 years old with advanced ASPS that has progressed on atezolizumab monotherapy.

SECONDARY OBJECTIVES:

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

II. Measure progression-free survival (PFS) time for patients receiving atezolizumab monotherapy or atezolizumab plus bevacizumab as determined by investigator using RECIST v 1.1.

III. Assess the number of activated CD8+ T cells infiltrating the tumor before and after treatment with atezolizumab monotherapy or atezolizumab plus bevacizumab, and correlate treatment-induced changes with clinical response.

IV. Measure and describe the atezolizumab pharmacokinetics (PK) and anti-drug antibodies (ADA) in patients ages 2-11 years old.

EXPLORATORY OBJECTIVES:

I. Compare RECIST v 1.1 vs immune RECIST (iRECIST) in patients with ASPS on atezolizumab and atezolizumab + bevacizumab.

II. Assess the post-progression response rate among patients who progress while on treatment holiday and then resume treatment.

III. Analyze the genomic and immune profiles of tumors expressing type 1 or type 2 ASPL-TFE3 fusions and correlate findings with response to atezolizumab or atezolizumab in combination with bevacizumab.

IV. Measure and describe the atezolizumab pharmacokinetics (PK) in patients \>= 12 years old.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients in arm I who do achieve disease progression may cross-over to arm II. Patients also undergo computed tomography (CT) imaging, and collection of blood and urine at baseline.

ARM II: Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT imaging, and collection of blood and urine at baseline.

After completion of study treatment, patients are followed up for 27-30 days. Patients who are progression-free at the end of a 2-year treatment holiday are followed every 6 months.

Testing Atezolizumab Alone or Atezolizumab Plus Bevacizumab in People With Advanced Alveolar Soft Part Sarcoma

A Phase 2 Study of Anti-PD-L1 Antibody (Atezolizumab) in Alveolar Soft Part Sarcoma

Will be evaluated using Response Evaluation Criteria in Solid Tumors version 1.1. 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.

Will be assessed using Response Evaluation Criteria in Solid Tumors version 1.1. 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.

Will be evaluated using Response Evaluation Criteria in Solid Tumors version 1.1. 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.

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.

Will be evaluated by immune Response Evaluation Criteria in Solid Tumors. 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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing Atezolizumab With or Without Selinexor in Patients >= 18 Years Old With Alveolar Soft Part Sarcoma, the Axiom Study	NCT05333458	Advanced Alveol... Advanced Soft T... Metastatic Alve... Unresectable Al...	Atezolizumab Biopsy Biospecimen Col... Computed Tomogr... Magnetic Resona... Selinexor	18 Years -	National Cancer Institute (NCI)
Testing Atezolizumab With or Without Selinexor in Patients >= 18 Years Old With Alveolar Soft Part Sarcoma, the Axiom Study	NCT05333458	Advanced Alveol... Advanced Soft T... Metastatic Alve... Unresectable Al...	Atezolizumab Biopsy Biospecimen Col... Computed Tomogr... Magnetic Resona... Selinexor	18 Years -	National Cancer Institute (NCI)
Testing Atezolizumab Alone or Atezolizumab Plus Bevacizumab in People With Advanced Alveolar Soft Part Sarcoma	NCT03141684	Metastatic Alve... Unresectable Al...	Atezolizumab Bevacizumab Biospecimen Col... Computed Tomogr...	2 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for unresectable alveolar soft part sarcoma