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)

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Nutritional and Metabolic Diseases

Ichthyosis, X-Linked

Pembrolizumab

Axitinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants in this group will receive combination treatment of Axitinib plus Pembrolizumab for up to 2 years followed by monotherapy of Axitinib until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.

Expansion cohort for up to 10 additional patients with alveolar soft part sarcoma. Participants in this group will receive combination treatment of Axitinib plus Pembrolizumab for up to 2 years followed by monotherapy of Axitinib until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.

5 mg tablets twice daily oral dose administered for 7 consecutive weeks on Cycle 1. A safety lead-in consisting of the initial five patients, intrapatient dose escalation of Axitinib will be permitted based on the absence of predefined toxicities. Twice daily oral dose between 2 mg to 10 mg Axitinib tablets will be administered on subsequent 6 week cycles until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.

200 mg intravenous infusion administered every 21 weeks beginning week 2 of Cycle 1 for a maximum of up to 2 years or until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.

Jonathan C Trent, MD

The purpose of this research study is to test if Axitinib together with Pembrolizumab can slow tumor growth and know the side effects of the combination treatment.

Arm 2, the Axitinib Plus Pembrolizumab Expansion Cohort, did not open.

Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma and Other Soft Tissue Sarcomas

A Phase II Trial of Concurrent Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma (ASPS) and Other Soft Tissue Sarcomas (STS)

Percentage of participants who are disease progression free 3 months after initiation of therapy. Disease progression will be evaluated from imaging measures using the Response Evaluation Criteria for Solid Tumors (RECIST) 1.1.

Objective Response Rate (ORR) is defined as achieving complete response (CR) or partial response (PR) from imaging measures using (RECIST) 1.1.

CBR is defined as achieving complete response (CR), partial response (PR) or stable disease (SD) from imaging measures using (RECIST) 1.1.

Time to progression (TTP) is defined as time from treatment initiation to first occurrence of progression by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 or death.

OS is (OS) is defined as the elapsed time from treatment initiation to death from any cause, whichever is earlier. Patients alive or those lost to follow-up will be censored at the last date of contact (or last date known to be alive).

The number of participants experiencing serious adverse events (SAEs), dose-limiting toxicities (DLTs), and grade 3 or higher treatment-emergent adverse events (AEs). AEs, SAEs and DLTs will be evaluated by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. Treatment-emergent adverse events are those found to be definitely, probably and possibly related to study therapy.

Merck Sharp & Dohme LLC

Pfizer

Jonathan Trent, MD, PhD

Professor of Medicine

In this protocol, adverse events include only treatment-emergent adverse events. Adverse events that are definitely, probably or possible related to study therapy are reported.

Participants in this group will receive combination treatment of Axitinib plus Pembrolizumab for up to 2 years followed by monotherapy of Axitinib until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.

Axitinib: 5 mg tablets twice daily oral dose administered for 7 consecutive weeks on Cycle 1. A safety lead-in consisting of the initial five patients, intrapatient dose escalation of Axitinib will be permitted based on the absence of predefined toxicities. Twice daily oral dose between 2 mg to 10 mg Axitinib tablets will be administered on subsequent 6 week cycles until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.

Pembrolizumab: 200 mg intravenous infusion administered every 21 weeks beginning week 2 of Cycle 1 for a maximum of up to 2 years or until withdrawal of consent, disease progression and/or unacceptable toxicity as assessed by treating physician, whichever occurs first.

Axitinib Plus Pembrolizumab Group

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Jonathan Trent MD

Evaluable participants received 80% of scheduled axitinib doses and two infusions of pembrolizumab, have measurable disease at baseline and at least one post-baseline disease assessment.

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)
Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma and Other Soft Tissue Sarcomas	NCT02636725	Alveolar Soft P... Soft Tissue Sar...	Axitinib Pembrolizumab	16 Years -	University of Miami
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)
Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma and Other Soft Tissue Sarcomas	NCT02636725	Alveolar Soft P... Soft Tissue Sar...	Axitinib Pembrolizumab	16 Years -	University of Miami

Spots Global Cancer Trial Database for advanced alveolar soft part sarcoma