Metastatic LeiomyosarcomaPhase 2NCT06571734
XL092 (Zanzalintinib) for the Treatment of Patients With Metastatic or Unresectable Leiomyosarcoma, Bone Sarcoma or Translocation-associated Soft Tissue Sarcoma
A Phase 2 study testing Biospecimen Collection, Computed Tomography and Echocardiography in people with Metastatic Leiomyosarcoma and Unresectable Leiomyosarcoma, run by Northwestern University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Leiomyosarcoma, Unresectable Leiomyosarcoma, Bone Sarcoma
- What is being tested?
- Biospecimen Collection, Computed Tomography and Echocardiography
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Sep 2024to 1 Jul 2033
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 at least 2 or more lines of antineoplastic treatment, but no more than 2 lines of treatment can be a tyrosine kinase inhibitor (TKI).
- Patients must have histologically confirmed diagnosis of metastatic or unresectable bone sarcoma. 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 at least 1 or more prior lines of antineoplastic treatment, but no more than 2 lines of treatment can be a tyrosine kinase inhibitor (TKI).
- Inclusion Criteria For Cohort 3 - Translocation-associated Soft Tissue Sarcoma:
- Patients must have histologically confirmed diagnosis of metastatic or unresectable translocation-associated soft tissue sarcoma (TAS). Pathology must have been reviewed at a National Comprehensive Cancer Network (NCCN) designated cancer center such as Northwestern University's Lurie Cancer Center.
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- Patients must have undergone at least 1 or more prior lines of antineoplastic treatment, but no more than 2 lines of treatment can be a tyrosine kinase inhibitor (TKI).
- 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.
- Absolute neutrophil count (ANC) ≥ 1,500/mcL (without granulocyte colony-stimulating factor support within 21 days of screening sample collection)
- Hemoglobin (Hgb) ≥ 9 g/dL without transfusion within 21 days of screening laboratory sample collection
- Platelets (PLT) ≥ 100,000/mm^3 (> 100 GI/L) without transfusion within 21 days of screening laboratory sample collection
- International normalized ratio (INR) ≤ 1.5 ULN 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
- Creatinine clearance ≥ 40mL/min
- Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg ( ≤ 113.12 mg/mmol)
- Patient of child-bearing potential (POCBP) and any of their partners with sperm-producing reproductive capability must agree to use a highly effective method of contraception throughout the course of the study and for 186 days after the last dose of treatment. Additional contraceptive method, such as a barrier method (e.g., condom) is also required
- Patients with sperm-producing reproductive capacity (PWSPRC) treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence), with partners of childbearing potential from time of informed consent, for the duration of study participation, and for 96 days following completion of therapy
- Patients must have ejection fraction > 50% by either MUGA scan or echocardiogram.
- Patients must be capable of understanding and complying with the protocol requirements.
- Patients must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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 as anticancer treatments.
- Patients who have had prior chemotherapy, or radiation therapy within 4 weeks prior to start of study treatment 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
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- 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: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed. 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 start of treatment. 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:
- Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias (e.g., ventricular flutter, ventricular fibrillation, Torsades de pointes)
- Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic of > 90 mm Hg diastolic despite optimal antihypertensive treatment
- Stroke (including transient ischemic attack [TIA]), myocardial infarction, or other clinically significant ischemic events within 12 months prior to first dose of study treatment. Note: Patients who did not require prior anticoagulant therapy may be eligible must be discussed and approved by the principal investigator (PI)
- Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous or non-cerebrovascular accident (CVA)/TIA arterial thromboembolic events within 6 months before to first dose of study treatment.
- Prior history of myocarditis
- Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
- Tumors invading the GI tract from external viscera
- Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis
- Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess must be confirmed prior to first dose of study treatment
- Known gastric or esophageal varices
- Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months unless cause of obstruction is definitively managed and subject is asymptomatic
- Patients with clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 84 days prior to registration.
- Symptomatic cavitating pulmonary lesions or endobronchial disease (asymptomatic or radiated lesions allowed).
- Lesions invading major blood vessel including but not limited to inferior vena cava, pulmonary artery, or aorta.
- Note: Patients with intravascular tumor extension (e.g., tumor thrombus in renal vein or inferior vena cava) may be eligible following PI approval
- Patients who are capable of donating eggs for the purpose of reproduction must not do so throughout the course of the study and for 186 days after the last dose of treatment
- Patients who are capable of donating sperm for the purpose of reproduction must not do so throughout the course of the study and for 96 days after the last dose of treatment
- Other clinically significant disorders that would preclude safe study participation, including, but not limited to:
- Active infection requiring systemic treatment. Note: This criterion applies only at enrollment; if a patient develops an infection while on study treatment, they may continue to receive study treatment. Note: prophylactic antibiotic treatment is allowed
- Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness
- Known positive test for or suspected infection with SARS-CoV-2 within one month prior to enrollment. Note: Demonstration that the patient has fully recovered from the infection is required to be eligible for enrollment
- Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if they are due to tumor-associated skin lesions
- Malabsorption syndrome
- Pharmacologically uncompensated, symptomatic hypothyroidism
- Moderate to severe hepatic impairment (Child-Pugh B or C)
- Requirement for hemodialysis or peritoneal dialysis
- History of solid organ or allogenic stem cell transplant
- Recent surgery within the following parameters:
- Major surgery (e.g., GI surgery or removal/biopsy of brain metastasis) within 8 weeks prior to study treatment
- Minor surgery (e.g., simple excision, tooth extraction) within 5 days prior to first dose of study treatment. Note: if a patient has had a recent surgery outside of the proscribed interval, complete wound healing from said surgery must have occurred prior to first dose of study treatment. Note: Fresh tumor biopsies should be performed at least 5 days prior to registration. Patients with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible
- Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms within 14 days per electrocardiogram (ECG) prior to first dose of study treatment Note: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility
- Patients with any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) grade > 1 at baseline from a previous anticancer therapy, with the following exceptions:
- Alopecia, vitiligo, and the laboratory values
- Patients with grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the treating physician
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with XL092 may be included only after consultation with the principal investigator
- Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to XL092
- Patients who are pregnant (positive serum or urine test within 72 hours prior to enrollment) or nursing. Pregnant people are excluded from this study because XL092 is a next-generation tyrosine kinase inhibitor with 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 nursing parent with XL092, breastfeeding should be discontinued if the nursing parent is treated with XL092. Note: If a urine pregnancy test is positive or cannot be confirmed negative, a serum pregnancy test will be required
- Patients with psychiatric illness/social situations that would limit compliance with study requirements, per the opinion of the treating investigator
- XL092 is administrated orally; patients who are unable to swallow, retain, and/or absorb pills are not eligible for this study
- Patients who are currently participating in or have participated in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of treatment
- Other conditions which, in the opinion of the Investigator, would compromise the safety of the patient or the patient's ability to complete the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Pedro Hermida de Viveiros, (312) 926-9636, cancer@northwestern.edu
Pedro Hermida de Viveiros, MD
About this study
Official title: A Non-Randomized, Open-label Phase II Trial Testing the Activity of XL092 (Zanzalintinib) in Patients With Advanced Leiomyosarcoma, Bone Sarcoma or Translocation-associated Soft Tissue Sarcoma
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. The trial has now been expanded to treat additional sarcoma types that are sensitive to tyrosine kinase inhibitors (TKIs) such as translocation-associated soft tissue sarcoma (such as synovial sarcoma), and bone sarcoma (including osteosarcoma and Ewing sarcoma).
Read the detailed description
PRIMARY OBJECTIVE:
- Evaluate 6-month progression-free survival (PFS) of patients with advanced leiomyosarcoma (LMS), bone sarcoma, or translocation-associated soft tissue sarcoma (TAS) who have been treated with zanzalintinib (XL092) monotherapy.
SECONDARY OBJECTIVES:
- Evaluate median progression-free survival (PFS) in patients with advanced leiomyosarcoma (LMS), bone sarcoma, or translocation-associated soft tissue sarcoma (TAS) who have been treated with XL092 monotherapy.
II. Determine overall survival (OS) in patients with advanced leiomyosarcoma (LMS), bone sarcoma, or translocation-associated soft tissue sarcoma (TAS) who have been treated with XL092 monotherapy.
III. Determine overall response rate (ORR) in patients with advanced leiomyosarcoma (LMS), bone sarcoma, or translocation-associated soft tissue sarcoma (TAS) who have been treated with XL092 monotherapy.
IV. Assess duration of response (DOR) in patients with advanced leiomyosarcoma (LMS), bone sarcoma, or translocation-associated soft tissue sarcoma (TAS) who have been treated with XL092 monotherapy.
- Assess toxicity of XL092 in patients with advanced leiomyosarcoma (LMS), bone sarcoma, or translocation-associated soft tissue sarcoma (TAS) who have been treated with such as monotherapy.
OUTLINE:
Patients receive XL092 orally (PO) once daily (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 echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening and then as clinically indicated, and blood sample collection on study and computed tomography (CT) throughout the study.
After completion of study treatment, patients complete a 30 day follow-up visit and will then follow up every 12 weeks for 2 years and then every 6 months for up to 5 years from start of study treatment.
- Conditions
- Metastatic Leiomyosarcoma, Unresectable Leiomyosarcoma, Bone Sarcoma, Translocation-associated Soft Tissue Sarcoma, Synovial Sarcomas, Osteosarcoma Metastatic
- Being tested
- Biospecimen Collection, Computed Tomography, Echocardiography, Multigated Acquisition Scan, Zanzalintinib
- Medical subject headings
- Leiomyosarcoma, Bone Neoplasms, Sarcoma, Synovial, Sarcoma, Ewing, Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
EchocardiographyProcedure or surgery
Also called EC
Undergo ECHO
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA
ZanzalintinibDrug
Also called Multi-kinase Inhibitor XL092, XL 092, XL-092, XL092
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Drug: Zanzalintinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month Progression-Free Survival (PFS)
PFS data will be collected from baseline (first day of treatment) until the patient experiences disease progression, initiates subsequent anti-cancer therapy, completes 6 months of study participation, or experiences death from any cause (whichever is sooner).
Measured: Up to 6 months
Secondary outcomes (5)
Median PFS
Median PFS will be calculated as the overall PFS time as the time that elapses between initiation of trial therapy and first documented disease progression or death from any cause, whichever come first.
Measured: Up to 5 years
Overall Survival (OS)
OS will be calculated as the time that elapses between the day of patient registration and death from any cause.
Measured: Up to 5 years
Overall Response Rate (ORR)
ORR will be defined as the proportion of treated patients who experience an objective response (confirmed complete response or confirmed partial response per RECIST v 1.1.).
Measured: Up to 5 years
Duration of Response (DOR)
DOR will be calculated as the time that elapses between the day of first documented response to trial therapy (confirmed CR or confirmed PR, whichever is first recorded) and subsequent disease progression. DOR will be estimated as median and interquartile range or mean and a confidence interval depending on the distribution.
Measured: Up to 5 years
Incidence of Adverse Events (AEs)
Frequency of AES will be reported by type, severity (grade), timing, and attribution according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. AEs will be reported using descriptive statistics.
Measured: Up to 30 days after last dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2024
- Study start19 Sep 2024
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Jul 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic LeiomyosarcomaStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 73 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Pedro Hermida de Viveiros, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06571734
- Sponsor's protocol ID
- NU 23S03
- Other IDs
- P30CA060553, NCI-2024-06742, NU 23S03
- Status last verified
- Oct 2026
- First submitted
- 23 Aug 2024
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No