XL092 for the Treatment of Locally Advanced or Metastatic Radioiodine Refractory Differentiated Thyroid Cancer
A Phase 2 Open Label Study of XL092 as First Line Therapy in Radioiodine Refractory Differentiated Thyroid Cancer
4 other identifiers
interventional
33
1 country
1
Brief Summary
This phase II trial tests how well XL092 works for the treatment of patients with differentiated thyroid cancer that has not responded to previous treatment with radioiodine (radioiodine refractory) and that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). XL092 is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jun 2025
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 28, 2025
CompletedFirst Posted
Study publicly available on registry
May 6, 2025
CompletedStudy Start
First participant enrolled
June 6, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 11, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 11, 2030
June 11, 2025
June 1, 2025
3.3 years
April 28, 2025
June 7, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Progression free survival (PFS)
Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria. Median PFS at 12-months will be analyzed using the Kaplan-Meier method. The 12-month PFS estimate will be reported along with the confidence interval. Cox proportional hazards models will be applied to assess the impact of covariates such as age, sex, baseline disease severity, and genetic markers on PFS, when appropriate.
From the time of the first dose of XL092 to the first documentation of disease progression, initiation of subsequent anti-cancer therapy, completion of 12 months of participation, or death from any cause, whichever occurs first, assessed at 12 months
Secondary Outcomes (5)
Radiographic response rate
Up to 12 month follow-up
Overall PFS
From the first dose of XL092 to the date of the first progression event or death from any cause, assessed up to 12 month follow-up
Overall survival (OS)
From the start of treatment with XL092 to the date of death from any cause, assessed up to 12 month follow-up
Incidence of adverse events
Up to 30 days after the end of treatment
Changes in quality of life
Baseline to 12 month follow-up
Study Arms (1)
Treatment (XL092)
EXPERIMENTALPatients receive XL092 PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and x-ray imaging, and blood and urine sample collection throughout the study.
Interventions
Undergo blood and urine sample collection
Undergo CT scan
Undergo MRI
Undergo x-ray imaging
Given PO
Eligibility Criteria
You may qualify if:
- Patients must have a histologically confirmed locally advanced or metastatic, radioactive iodine (RAI) refractory, differentiated thyroid cancer (including papillary, follicular, and oncocytic/Hurthle cell, and poorly differentiated thyroid cancer \[PDTC\]), with progression within 12 months (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\] 1.1 response criteria) prior to study registration, and no prior therapy in the RAI-refractory setting and for which standard curative or palliative measures do not exist or are no longer effective.
- NOTE: RAI refractoriness is defined as absence of uptake of RAI on either a low-dose diagnostic test or a post-treatment RAI scan in measurable lesions or radiographic progression of disease within 12 months of the last course of RAI treatment despite the recorded uptake of RAI with that previous therapy or having a cumulative lifetime administered dose of ≥ 600mCi.
- Poorly differentiated thyroid cancer (PDTC) is typically classified as a type of differentiated thyroid cancer (as opposed to undifferentiated thyroid cancer or anaplastic thyroid cancer)
- Patients must have measurable disease according to RECIST v 1.1
- Patients must be age ≥ 18 years
- Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2
- Leukocytes (WBC) ≥ 3,000/mcL
- Absolute neutrophil count (ANC) ≥ 1,500/mcL
- Prophylactic use of granulocyte colony-stimulating factor (G-CSF) will not be allowed within 2 weeks of relevant screening laboratory testing. However, G-CSF may be employed in accordance with current American Society of Clinical Oncology (ASCO) guidelines for treatment-emergent neutropenia observed at any time during the study
- Hemoglobin (Hgb) ≥ 9 g/dL
- Prophylactic use of blood transfusions for anemia and thrombocytopenia is not allowed within 2 weeks prior to relevant screening laboratory testing, but such treatment is allowed for treatment-emergent anemia or thrombocytopenia, as indicated by the current ASCO and American Association of Blood Banks guidelines
- Platelets (PLT) ≥ 100,000/mcL
- Prophylactic use of blood transfusions for anemia and thrombocytopenia is not allowed within 2 weeks prior to relevant screening laboratory testing, but such treatment is allowed for treatment-emergent anemia or thrombocytopenia, as indicated by the current ASCO and American Association of Blood Banks guidelines
- Total bilirubin ≤ 1.5 x Institutional upper limit of normal (ULN) ; for subjects with Gilbert's disease ≤ 3 x ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 3 x Institutional ULN
- +26 more criteria
You may not qualify if:
- Prior treatment with XL092 (zanzalintinib)
- Patient has hepatitis B
- Patient has hepatitis C.
- NOTE: Patients with treated hepatitis C and positive hepatitis C virus (HCV) antibody test are eligible only if followed by a negative HCV ribonucleic acid (RNA) test and no ongoing anti-HCV therapy. The HCV RNA test will be performed only for patients who have a positive HCV antibody test
- Patient is pregnant or nursing (lactating)
- NOTE: Pregnant patients are excluded from this study because XL092 is a tyrosine kinase inhibitor with the 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 mother with XL092, breastfeeding should be discontinued if the mother is treated with XL092
- Receipt of any type of small molecule kinase inhibitor treatment (including investigational kinase inhibitor) within 2 weeks before the first dose of study treatment
- Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational therapy or investigational device) within 4 weeks before the first dose of study treatment.
- NOTE: For patients that received nitrosoureas or mitomycin C, \< 6 weeks prior to planned treatment start date
- Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks before the first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment.
- NOTE: Patients with clinically relevant ongoing complications from prior radiation therapy are not eligible
- Previously identified allergy or hypersensitivity to components of the study treatment formulations, have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to XL092 (zanzalintinib)
- Concomitant anticoagulation with oral anticoagulants (e.g., warfarin or other coumarin-related agents, direct thrombin inhibitors, or anti-platelet agents such as clopidogrel, chronic use of aspirin above low dose levels for cardio-protection per institutional practice).
- NOTE: Allowed anticoagulants are the following: prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low molecular weight heparins (LMWH); Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.
- NOTE: Patients must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.
- +49 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Northwestern Universitylead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Northwestern University
Chicago, Illinois, 60611, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jochen H Lorch
Northwestern University
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
April 28, 2025
First Posted
May 6, 2025
Study Start
June 6, 2025
Primary Completion (Estimated)
September 11, 2028
Study Completion (Estimated)
September 11, 2030
Last Updated
June 11, 2025
Record last verified: 2025-06