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Neoadjuvant TreatmentPhase 2NCT06959511

Zanzalintinib for the Treatment of Advanced Thyroid Cancer Before Surgery

A Phase 2 study testing Zanzalintinib in people with Neoadjuvant Treatment and Thyroid Cancer, run by M.D. Anderson Cancer Center at 5 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoadjuvant Treatment, Thyroid Cancer
What is being tested?
Zanzalintinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
5 sitesUnited States
Study dates
22 Jul 2025to 1 Oct 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

None listed.

Who cannot join

  • 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.
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  • 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:
  • 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.
  • 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.
  • Moderate to severe hepatic impairment (Child-Pugh B or C).
  • Requirement for hemodialysis or peritoneal dialysis.
  • History of solid organ or allogeneic stem cell transplant.
  • Major surgery (as defined in Appendix B; e.g., GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose of study treatment. Minor surgery (e.g., simple excision, tooth extraction) within 5 days before first dose of study treatment. Fine needle aspiration and core biopsies are allowed on study drug without drug hold.Complete wound healing from major or minor surgery must have occurred at least prior to first dose of study treatment.
  • Note: Participants 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) before first dose of study treatment.
  • History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
  • Pregnant or lactating females.
  • Inability to swallow tablets or ingest a suspension either orally or by nasogastric (NG) or gastrostomy (PEG) tube.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations.
  • Another malignancy that requires active therapy and in the opinion of the Investigator would interfere with monitoring of radiologic assessments of response to Investigational Product, within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
  • Other conditions, which in the opinion of the Investigator, would compromise the safety of the participant or the participants ability to complete the study.

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Mark Zafereo, MD contact

713-563-9683

mzafereo@mdanderson.org

5 sites in 1 country

United States5 sites, 5 recruiting

  • University of Michigan

    Ann Arbor, Michigan, 48109

    Francis Worden, MD, 734-936-5281, fworden@med.umich.edu

    Francis Worden, MD

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Gregory Randolph, MD, 617-724-4000, gregory_randolph@meei.harvard.edu

    Recruiting

  • University of Virginia

    Charlottesville, Virginia, 22908

    Varinder Kaur, MD, 434-297-4054, vk4q@uvahealth.org

    Varinder Kaur, MD

    Recruiting

  • Cleveland Clinic Taussig Cancer Institute

    Cleveland, Ohio, 44195

    Jessica Geiger, MD, geigerj@ccf.org

    Jessica Geiger, MD

    Recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Mark Zafero, MD, 713-563-9683, mzafereo@mdanderson.org

    Mark Zafereo, MD

    Recruiting

Other trials in United States

About this study

Official title: ZAnzalintinib Neoadjuvant EValuation in Thyroid Oncology (ZANEVO)

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

Read the detailed description

Primary Objectives

  • To evaluate the efficacy of neoadjuvant zanzalintinib in DTC, non-RET-mutated MTC, and poorly differentiated thyroid cancer (PDTC) by overall objective response rate (overall ORR), defined as the proportion of participants who have a minor response (MR), partial response (PR), or complete response (CR) per RECIST. Participants with locally invasive extrathyroidal and/or extra nodal DTC, non- RET-mutated MTC or PDTC who have high surgical morbidity/complexity based on baseline radiographic assessment (as measured by Thyroid Neck Surgical Morbidity/Complexity Scoring, will be eligible for the study.

Hypothesis: Neoadjuvant administration of zanzalintinib will result in acceptable overall ORR (MR+PR+CR rate) for participants with locoregionally advanced DTC and non-RETmutated MTC, ultimately allowing patients to safely undergo complete gross surgical tumor resection with less surgical morbidity.

Secondary Objectives

  • To evaluate the efficacy of neoadjuvant zanzalintinib in DTC, non-RET-mutated MTC or PDTC by objective response rate (ORR) per modified neck RECIST.
  • To evaluate the safety profile of neoadjuvant zanzalintinib in thyroid cancer.
  • To evaluate the efficacy of neoadjuvant zanzalintinib on progression-free survival (PFS), including overall PFS and locoregional PFS.
  • To measure changes in expected and actual thyroid neck surgical morbidity/complexity scoring before and after zanzalintinib treatment.
  • To evaluate the efficacy of neoadjuvant zanzalintinib by surgical margin status.

Exploratory Objectives

  • To define and measure changes of patient-reported outcomes (PROs) and quality of life (QOL) as measured by MDASI-HN and EQ-5D in participants who receive zanzalintinib treatment.
  • To evaluate the efficacy of neoadjuvant zanzalintinib by pathologic response.
  • To evaluate the efficacy of neoadjuvant zanzalintinib by PET metabolic response.
Being tested
Zanzalintinib
Medical subject headings
Thyroid Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZanzalintinibDrug

    Given by po

Study groups in NCT06959511
Study groupRoleWhat they receive
Neoadjuvant with Zanzalintinib Followed by SurgeryExperimentalZanzalintinib 60 mg orally once daily on Days 1 to 28 of a 28-day cycle.
Receives: Drug: Zanzalintinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and adverse events

    Defined as the proportion of patients who have a MR, PR, or CR per modified RECIST 1.1. CR and PR are defined using the same criteria as in RECIST 1.1. MR is defined as a 15% or greater decrease in the sum of the longest diameters of target lesions but not a PR. The MR+PR+CR response rate will be determined by dividing the number of patients with modified RECIST-based MR, PR, or CR divided by the number of evaluable patients

    Measured: From baseline until completion of neoadjuvant therapy; an average of 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 May 2025
  2. Study start22 Jul 2025
  3. Primary completion1 Mar 2028 (estimated)
  4. Study completion1 Oct 2030 (estimated)

Resources

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
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06959511
Sponsor's protocol ID
2024-0308
Other IDs
NCI-2025-03105
Status last verified
Nov 2026
First submitted
28 Apr 2025
Last updated
5 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanzalintinib in people with Neoadjuvant Treatment and Thyroid Cancer, run by M.D. Anderson Cancer Center at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Mark Zafereo, MD (713-563-9683, mzafereo@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and adverse events (time frame: From baseline until completion of neoadjuvant therapy; an average of 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06959511.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.

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