XL092 (Zanzalintinib) for the Treatment of Patients With Metastatic or Unresectable Leiomyosarcoma

NCT06571734 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NU 23S03NCI-2024-06742STU00221266P30CA060553
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well zanzalintinib (XL092) works in treating patients with leiomyosarcoma that has spread from where it first started to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). Leiomyosarcomas are a type sarcoma that can occur in any location in the body, such as the uterus or in the abdomen. Current standard treatment for leiomyosarcoma only shows a progression-free survival of 4-6 months. XL092, a tyrosine kinase inhibitor, interferes with cell communication and growth and may prevent tumor growth. Giving XL092 may kill more tumor cells in patients with metastatic or unresectable leiomyosarcoma.

Conditions

Metastatic Leiomyosarcoma; Unresectable Leiomyosarcoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS will be defined as progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.other documented clinical or radiographic progression per physician judgment, or death due to disease.

  Up to 6 months

Secondary Outcomes (5)

• Median PFS

  Up to 5 years

• Overall survival (OS)

  Up to 5 years

• Overall response rate (ORR)

  Up to 5 years

• Duration of response (DOR)

  Up to 5 years

• Incidence of adverse events (AEs)

  Up to 30 days after last dose of study drug

Study Arms (1)

Treatment (XL092)

EXPERIMENTAL

Patients receive XL092 PO QD on days 1-14 of each cycle. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA at screening and then as clinically indicated, and blood sample collection on study and CT throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Drug: Zanzalintinib

Interventions

Computed Tomography PROCEDURE

Undergo CT

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, tomography

Treatment (XL092)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (XL092)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (XL092)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (XL092)

Zanzalintinib DRUG

Given PO

Also known as: Multi-kinase Inhibitor XL092, XL 092, XL-092, XL092

Treatment (XL092)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed leiomyosarcoma that has been clinically determined to be metastatic or unresectable. Pathology must have been reviewed at a National Comprehensive Cancer Network (NCCN) designated cancer center such as Northwestern University's Lurie Cancer Center
• Patients must have undergone 1 prior line of antineoplastic treatment, but no more than 2 lines of treatment can be a tyrosine kinase inhibitor
• Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Patients must be aged ≥ 18 years on day of signing any informed consent documents
• Patients must exhibit a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale or \> 70% on the Karnofsky Scale
• Leukocytes (white blood cells \[WBC\]) ≥ 3,000/mcL
• Absolute neutrophil count (ANC) ≥ 1,500/mcL (without granulocyte colony-stimulating factor support within 14 days of screening sample collection)
• Hemoglobin (Hgb) ≥ 9 g/dL without transfusion within 14 days of screening laboratory sample collection
• Platelets (PLT) ≥ 100,000/mm\^3 (\> 100 GI/L) without transfusion within 14 days of screening laboratory sample collection
• International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.2 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x institutional upper limit of normal ULN; for patients with Gilbert's disease, total bilirubin ≤ 3 x ULN
• Alanine aminotransferase (AST) ≤ 3 x institutional ULN
• Aspartate aminotransferase (ALT) ≤ 3 x institutional ULN
• Alkaline phosphatase (ALP) ≤ 3 x institutional ULN; for patients with documented bone metastasis, ALP ≤ 5 x ULN
• Serum creatinine ≤ 1.5 x institutional ULN OR calculated creatinine clearance ≥ 40 mL/min ( ≥ 0.67 mL/sec) using the Cockcroft-Gault equation

You may not qualify if:

• Patients who have received previous treatment with XL092
• Patients who have received any type of small-molecule kinase inhibitor (including an investigational kinase inhibitor) within 14 days prior to study day 1 treatment
• Patients who have received \> 2 prior tyrosine kinase inhibitor therapies
• Patients who have had prior chemotherapy, or radiation therapy within 4 weeks prior to study day 1 unless they have recovered from their prior therapy (toxicity and/or complications) such that they now meet all other eligibility criteria
• Patients who have received radiation therapy for bone metastasis within 14 days prior to registration
• Patients who have undergone systemic treatment with radionuclides within 6 weeks (42 days) before first dose of study treatment
• Patients with clinically relevant complications from prior radiation therapy requiring ongoing therapy, per the opinion of the treating investigator enrolling the patient
• Patients with a known prior or concurrent malignancy that is progressing or requires active treatment within 2 years of first dose of study treatment. Note: The following exceptions may be made:
• For patients with malignancies like basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer; or superficial skin cancers, localized low-grade tumors deemed cured and not treated with systemic therapy, and incidentally diagnosed prostate cancer if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6
• For patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Patients with known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment. Note: Patients with an incidental finding of an isolated brain lesion \< 1 cm in diameter may be eligible after principal investigator approval if the lesion is radiographically stable for 4 weeks before first dose and does not require treatment per Investigator judgement. Note: Eligible patients must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment
• Patients who are on concomitant anticoagulation therapy with oral anticoagulants (e.g., warfarin or direct thrombin and factor Xa inhibitors) and platelet inhibitors (e.g., clopidogrel). Note: Allowed anticoagulants are low-dose aspirin for cardioprotection (per local applicable guidelines) and low molecular weight heparins (LMWH). Therapeutic doses of LMWH are not permitted in patients with brain metastases. Note: Patients must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first study treatment, whichever is longer
• Patients who are taking any complementary medications (e.g., herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks (14 days) prior to registration. Note: taking complementary medications to treat symptoms of the cancer is allowed
• The patient has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

MeSH Terms

Conditions

Leiomyosarcoma

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Pedro Hermida de Viveiros, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

3126951301; cancer@northwestern.edu

Study Design

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

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 26, 2024
• Study Start: September 19, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (1)