RECRUITING

Zanzalintinib for the Treatment of Advanced Thyroid Cancer Before Surgery

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

Neoadjuvant Treatment With Zanzalintinib for Advanced Thyroid Cancer

Quick Facts

Study Start:2025-07-22

Study Completion:2029-10-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06959511

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
Age 18 years or older Willing and able to provide informed consent Able to understand and follow study procedures Stable medical condition	1. Medullary thyroid cancer participants with germline RET or known somatic RET mutations. 2. Prior treatment with zanzalintinib. 3. Prior treatment with a tyrosine kinase inhibitor. 4. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment. 5. 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. 6. 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. 7. Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin inhibitors) and platelet inhibitors (e.g., clopidogrel). 1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH). 2. 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. 8. 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. 9. The participant has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: 10. 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. 11. 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. 12. 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. 13. Other clinically significant disorders that would preclude safe study participation. 1. Active infection requiring systemic treatment. Note: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are allowed. 2. 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. 3. Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions. 4. Malabsorption syndrome. 5. Uncontrolled symptomatic hyperthyroidism or hypothyroidism. 6. Uncontrolled symptomatic hypercalcemia or hypocalcemia. 7. Moderate to severe hepatic impairment (Child-Pugh B or C). 8. Requirement for hemodialysis or peritoneal dialysis. 9. History of solid organ or allogeneic stem cell transplant. 14. 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. 15. Corrected QT interval calculated by the Fridericia formula (QTcF) \> 480 ms within 14 days per electrocardiogram (ECG) before first dose of study treatment. 16. History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent. 17. Pregnant or lactating females. 18. Inability to swallow tablets or ingest a suspension either orally or by nasogastric (NG) or gastrostomy (PEG) tube. 19. Previously identified allergy or hypersensitivity to components of the study treatment formulations. 20. 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. 21. Other conditions, which in the opinion of the Investigator, would compromise the safety of the participant or the participants ability to complete the study.

Inclusion Criteria

Exclusion Criteria

Age 18 years or older
Willing and able to provide informed consent
Able to understand and follow study procedures
Stable medical condition

1. Medullary thyroid cancer participants with germline RET or known somatic RET mutations.
2. Prior treatment with zanzalintinib.
3. Prior treatment with a tyrosine kinase inhibitor.
4. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
5. 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.
6. 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.
7. Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin inhibitors) and platelet inhibitors (e.g., clopidogrel).
1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
2. 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.
8. 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.
9. The participant has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
10. 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.
11. 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.
12. 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.
13. Other clinically significant disorders that would preclude safe study participation.
1. Active infection requiring systemic treatment. Note: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are allowed.
2. 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.
3. Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.
4. Malabsorption syndrome.
5. Uncontrolled symptomatic hyperthyroidism or hypothyroidism.
6. Uncontrolled symptomatic hypercalcemia or hypocalcemia.
7. Moderate to severe hepatic impairment (Child-Pugh B or C).
8. Requirement for hemodialysis or peritoneal dialysis.
9. History of solid organ or allogeneic stem cell transplant.
14. 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.
15. Corrected QT interval calculated by the Fridericia formula (QTcF) \> 480 ms within 14 days per electrocardiogram (ECG) before first dose of study treatment.
16. History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
17. Pregnant or lactating females.
18. Inability to swallow tablets or ingest a suspension either orally or by nasogastric (NG) or gastrostomy (PEG) tube.
19. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
20. 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.
21. Other conditions, which in the opinion of the Investigator, would compromise the safety of the participant or the participants ability to complete the study.

Contacts and Locations

Study Contact

Mark Zafereo, MD

CONTACT

713-563-9683

mzafereo@mdanderson.org

Principal Investigator

Mark Zafereo, MD

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Mark Zafereo, MD, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07-22

Study Completion Date2029-10-01

Study Record Updates

Study Start Date2025-07-22

Study Completion Date2029-10-01

Terms related to this study

Additional Relevant MeSH Terms

Neoadjuvant Treatment
Thyroid Cancer