Trial Title:
XL092 (Zanzalintinib) for the Treatment of Patients With Metastatic or Unresectable Leiomyosarcoma
NCT ID:
NCT06571734
Condition:
Metastatic Leiomyosarcoma
Unresectable Leiomyosarcoma
Conditions: Official terms:
Leiomyosarcoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (XL092)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (XL092)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Treatment (XL092)
Other name:
EC
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA
Arm group label:
Treatment (XL092)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide Ventriculography
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Intervention type:
Drug
Intervention name:
Zanzalintinib
Description:
Given PO
Arm group label:
Treatment (XL092)
Other name:
Multi-kinase Inhibitor XL092
Other name:
XL 092
Other name:
XL-092
Other name:
XL092
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.
Detailed description:
PRIMARY OBJECTIVE:
I. Evaluate 6-month progression-free survival (PFS) of patients with advanced
leiomyosarcoma (LMS) who have been treated with zanzalintinib (XL092) monotherapy.
SECONDARY OBJECTIVES:
I. Evaluate median progression-free survival (PFS) in patients with advanced LMS who have
been treated with XL092 monotherapy.
II. Determine overall survival (OS) in patients with advanced LMS who have been treated
with XL092 monotherapy.
III. Determine overall response rate (ORR) in patients with advanced LMS who have been
treated with XL092 monotherapy.
IV. Assess duration of response (DOR) in patients with advanced LMS who have been treated
with XL092 monotherapy.
V. Assess toxicity of XL092 in patients with advanced LMS 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 are followed up at 30 days, then every 12
weeks for 2 years followed by every 6 months for up to 5 years from start of study
treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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 > 2 prior lines 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
- Creatinine clearance ≥ 40mL/min
- Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg ( ≤ 113.12 mg/mmol)
- INR (or prothrombin time [PT] or partial thromboplastin time [PTT]; one will be
used) ≤ 1.5
- aPTT ≤ 1.5 x ULN (unless patient is receiving anticoagulant therapy as long as PT or
PTT is within therapeutic range of intended use of anticoagulants [within 10 days of
treatment initiation])
- 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 120 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
Exclusion Criteria:
- 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:
- 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
- Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease
manifestation
- 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 10 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 7 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Seth M. Pollack
Phone:
312-695-6180
Email:
seth.pollack@northwestern.edu
Investigator:
Last name:
Seth M. Pollack, MD
Email:
Principal Investigator
Start date:
September 19, 2024
Completion date:
July 1, 2026
Lead sponsor:
Agency:
Northwestern University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Northwestern University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06571734
