Zanzalintinib for Thyroid Cancer

Overseen By Mark Zafereo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticoagulants, Platelet inhibitors, Cytotoxics, others

Disqualifiers: RET mutations, Brain metastases, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment, zanzalintinib, combined with surgery for advanced thyroid cancer. Researchers aim to determine the efficacy and safety of this combination. The trial targets individuals with specific types of thyroid cancer that have spread to nearby areas or recurred after treatment. Participants should not have specific mutations in their cancer or have received certain cancer drugs previously. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like oral anticoagulants and some complementary medicines close to the start of the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that zanzalintinib is likely to be safe for humans?

Research shows that zanzalintinib is under investigation as a treatment for advanced thyroid cancer. Although specific safety information for zanzalintinib is not yet available, similar drugs for thyroid cancer have shown manageable side effects. This suggests that zanzalintinib might also be well-tolerated.

The trial is in phase 2, indicating that earlier studies have already tested the treatment for safety. This phase now assesses its effectiveness and typically includes more participants to gather additional safety information.

Prospective participants should discuss potential risks and benefits with their healthcare provider to determine if this treatment is suitable for them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for thyroid cancer, which often involve surgery, radioactive iodine, and hormone therapy, Zanzalintinib is an oral medication that targets cancer cells directly. This drug is unique because it works by inhibiting specific proteins that the cancer cells need to grow, potentially leading to more targeted and effective treatment. Researchers are excited about Zanzalintinib because it could offer a less invasive option that fits smoothly into a patient's daily routine, while potentially improving outcomes by directly hitting the cancer’s growth mechanisms.

What evidence suggests that zanzalintinib might be an effective treatment for thyroid cancer?

Research has shown that zanzalintinib may help treat advanced thyroid cancer. In a previous study, this drug shrank tumors in 38% of patients and prevented cancer progression in 88% of patients. In this trial, participants will receive zanzalintinib as a neoadjuvant treatment before surgery. Zanzalintinib blocks signals that tumors use to grow. These findings suggest that the drug could be useful in managing advanced thyroid cancer before surgery. ^{1 2 4 5 6}

Who Is on the Research Team?

Mark Zafereo, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with advanced thyroid cancer who are candidates for surgery. Specific eligibility criteria are not provided, but typically participants must be in good health aside from their thyroid condition and meet certain age and medical requirements.

Inclusion Criteria

I have advanced thyroid cancer without a specific genetic mutation.

My thyroid cancer diagnosis is confirmed by lab tests.

I have recovered from previous treatment side effects, or they are mild and under control.

Exclusion Criteria

My medullary thyroid cancer is caused by a specific genetic change.

My brain metastases have been treated and stable for at least 4 weeks.

I do not have any severe, uncontrolled health conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant zanzalintinib 100 mg orally once daily on Days 1 to 28 of a 28-day cycle

4 weeks

4 visits (in-person)

Surgery

Participants undergo surgical tumor resection after treatment with zanzalintinib

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment and surgery

48 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Zanzalintinib

Trial Overview

The study is testing the effectiveness of a drug called Zanzalintinib as a pre-surgery (neoadjuvant) treatment for advanced thyroid cancer. The safety of this medication will also be evaluated during the trial.

How Is the Trial Designed?

Group I: Neoadjuvant with Zanzalintinib Followed by Surgery Experimental Treatment 1 Intervention

Zanzalintinib 100 mg orally once daily on Days 1 to 28 of a 28-day cycle.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Published Research Related to This Trial

Thyroid carcinoma, particularly differentiated types, can often be treated effectively with surgery and radioactive iodine, but some aggressive forms like anaplastic and medullary thyroid carcinomas are resistant to current treatments, highlighting the need for new therapies.

Targeting specific genetic mutations, such as those in the RET proto-oncogene and B-RAF, offers promising avenues for new treatments, with drugs like ZD 6474 showing potential in preclinical models and ongoing trials for B-RAF inhibitors planned in thyroid cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New molecular targeted therapies in thyroid cancer. Milano, A., Chiofalo, MG., Basile, M., et al.[2021]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06959511

Zanzalintinib for the Treatment of Advanced Thyroid ...

To evaluate the efficacy of neoadjuvant zanzalintinib in DTC, non-RET-mutated MTC, and poorly differentiated thyroid cancer (PDTC) by overall objective response ...

2.

ir.exelixis.com

ir.exelixis.com/news-releases/news-release-details/exelixis-announces-encouraging-results-expansion-cohort-phase-1b

Press Release - Exelixis, Inc.

Results for Exelixis' next-generation tyrosine kinase inhibitor demonstrated an objective response rate of 38% and a disease control rate of 88% –.

3.

withpower.com

withpower.com/trial/phase-2-thyroid-diseases-9-2025-44af7

Zanzalintinib for Thyroid Cancer

Trial Overview The study is testing the effectiveness of a drug called Zanzalintinib as a pre-surgery (neoadjuvant) treatment for advanced thyroid cancer. The ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06959641

XL092 for the Treatment of Locally Advanced or Metastatic ...

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 ...

5.

targetedonc.com

targetedonc.com/view/novel-tki-zanzalintinib-confers-promising-antitumor-activity-in-advanced-ccrcc

Novel TKI Zanzalintinib Confers Promising Antitumor ...

When cabozantinib was included, the response rate was 35% with a disease control rate of 92%. Once cabozantinib was excluded, the response rate ...

6.

merck.com

merck.com/news/exelixis-and-merck-sign-clinical-development-collaboration-to-evaluate-investigational-zanzalintinib-in-combination-with-keytruda-pembrolizumab-in-head-and-neck-cancer-and-in-combination-with/

Exelixis and Merck Sign Clinical Development ...

... cancer diagnosed and more than 155,953 deaths from the disease in 2022. About zanzalintinib. Zanzalintinib inhibits multiple cancer-related pathways that ...