Zanzalintinib for the Treatment of Advanced Thyroid Cancer Before Surgery

Recruiting now · Phase 2

Conditions studied: Neoadjuvant Treatment, Thyroid Cancer

In brief

To look at the effectiveness of zanzalintinib, followed by surgery, in treating advanced thyroid cancer. The safety of this treatment will also be studied.

Key facts

Study ID

NCT06959511

Run by

M.D. Anderson Cancer Center

People needed

45

Starts

2025-07-22

Expected to finish

2030-10-01

Last updated by the study team

2026-07-28

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Medullary thyroid cancer participants with germline RET or known somatic RET mutations.
• Prior treatment with zanzalintinib.
• Prior treatment with a tyrosine kinase inhibitor.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.
• Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin inhibitors) and platelet inhibitors (e.g., clopidogrel).
• Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose 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: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.
• Any complementary medications (e.g., herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
• The participant has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a. Unstable or deteriorating cardiovascular disorders: i. Congestive heart failure New York Heart Association class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (e.g., ventricular flutter, ventricular fibrillation, Torsades de pointes). ii. Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment. iii. Stroke (including transient ischemic attack [TIA]), myocardial infarction, or other clinically significant arterial thrombotic and/or ischemic event within 6 months before first dose of study treatment.
• iv. Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous events within 3 months before to first dose of study treatment. Note: Subjects with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and 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: Participants who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Principal Investigator.
• 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 12 weeks before first dose of study treatment.
• Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed. Intratracheal disease is allowed, as long as the endotracheal disease is not associated with major bleeding episodes.
• Lesions invading major blood vessel including, but are not limited to, inferior vena cava, pulmonary artery, or aorta. Note: Subjects with internal jugular vein involvement or tumor thrombus in the neck are eligible. Additionally, subjects with intravascular tumor extension (e.g., tumor thrombus in renal vein or inferior V. cava) may be eligiblefollowing Principal Investigator approval.
• Other clinically significant disorders that would preclude safe study participation.
• Active infection requiring systemic treatment. Note: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are allowed.
• Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)- related illness except for subjects meeting all of the following criteria: (1) on stable anti-retroviral therapy; (2) CD4+ T cell count ≥ 200/μL; and (3) an undetectable viral load. Note: HIV testing will be performed at screening if and as required by local regulation. Note: To be eligible, participants taking CYP inhibitors (e.g., zidovudine, ritonavir, cobicistat, didanosine) or CYP3 inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies (ART) must have been received for at least 4 weeks prior to the first dose. Note: CD4+ T cell counts and viral load are monitored per standard of care by the local health care provider.
• Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.
• Malabsorption syndrome.
• Uncontrolled symptomatic hyperthyroidism or hypothyroidism.
• Uncontrolled symptomatic hypercalcemia or hypocalcemia.

Where it is running

• University of Michigan — Ann Arbor, Michigan, United States (enrolling)
• Cleveland Clinic Taussig Cancer Institute — Cleveland, Ohio, United States (enrolling)
• MD Anderson Cancer Center — Houston, Texas, United States (enrolling)
• University of Virginia — Charlottesville, Virginia, United States (enrolling)

Full record on ClinicalTrials.gov

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