Zanzalintinib for Neuroendocrine Tumors

Not yet recruiting at 2 trial locations

Overseen By Nikolaos Trikalinos, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Oral anticoagulants, Platelet inhibitors

Disqualifiers: 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether zanzalintinib, a new potential drug, can slow the progression of neuroendocrine tumors, a type of cancer affecting certain hormone-producing cells, after initial chemotherapy. It targets individuals with confirmed high-grade cancer who have completed an initial chemotherapy course with stable results or partial improvement. Participants must have measurable disease and must not have previously received treatment with zanzalintinib or cabozantinib. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of a potentially effective therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain oral anticoagulants and must stop them at least 3 days or 5 half-lives before starting the trial. If you are on somatostatin analogue therapy for well-differentiated high-grade tumors, you can continue it.

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

Previous studies have shown that zanzalintinib demonstrates promise in terms of safety when combined with other treatments. For instance, when used with atezolizumab, zanzalintinib lowered the risk of death compared to regorafenib, suggesting it can be relatively safe with other medications. Additionally, when combined with nivolumab, many patients experienced positive effects without serious health issues.

These findings offer some reassurance about its safety, but it's important to remember that zanzalintinib alone might have different effects. Always discuss potential side effects and safety concerns with healthcare providers before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Zanzalintinib is unique because it introduces a new approach to treating neuroendocrine tumors by targeting specific pathways involved in tumor growth. Unlike standard treatments like somatostatin analogs or chemotherapy, which focus on controlling symptoms or destroying rapidly dividing cells, Zanzalintinib directly inhibits tyrosine kinases, which play a crucial role in the development and spread of these tumors. Researchers are excited about Zanzalintinib's potential to offer a more targeted and potentially less toxic treatment option, with the convenience of oral administration once daily.

What evidence suggests that zanzalintinib might be an effective treatment for neuroendocrine tumors?

Research has shown that zanzalintinib may help treat neuroendocrine tumors. One study demonstrated that, when combined with nivolumab, it resulted in a 63% rate of significant tumor shrinkage and a 90% rate of halting tumor growth. These findings suggest that zanzalintinib could effectively control tumor growth. In this trial, participants will receive zanzalintinib alone to evaluate its effectiveness in treating hard-to-treat neuroendocrine tumors. These results indicate that zanzalintinib might be a strong option for slowing tumor progression. ^{1 4 6 7 8}

Who Is on the Research Team?

Nikolaos Trikalinos, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with high-grade neuroendocrine tumors, excluding lung and Merkel cell cancer. Participants must have stable disease or partial response after initial chemo, be able to consent, not pregnant, and agree to use contraception. They should have good organ function and performance status.

Inclusion Criteria

Measurable disease per RECIST 1.1

Ability to understand and willingness to sign an IRB approved written informed consent document

I am not pregnant and can have children.

Exclusion Criteria

Pregnant and/or breastfeeding

History of allergic reactions attributed to compounds of similar composition to zanzalintinib

Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms within 14 days before C1D1

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive initial cytotoxic chemotherapy

Varies

Maintenance Treatment

Participants receive zanzalintinib maintenance therapy in 28-day cycles

Up to 3 years

Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Zanzalintinib

Trial Overview

The study tests if Zanzalintinib can extend the time patients live without their cancer getting worse after initial chemotherapy. Patients will receive Zanzalintinib as a maintenance therapy to see if it helps control tumor growth better than current standard care.

How Is the Trial Designed?

Group I: Zanzalintinib Experimental Treatment 1 Intervention

Zanzalintinib 60 mg taken by mouth once daily in 28-day cycles for up to 3 years.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

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

In a phase II study involving 109 patients with advanced neuroendocrine tumors, sunitinib demonstrated a 16.7% objective response rate in pancreatic endocrine tumor patients and 2.4% in carcinoid patients, with a significant proportion of patients experiencing stable disease.

The treatment resulted in a median time to tumor progression of 7.7 months for pancreatic neuroendocrine tumors and 10.2 months for carcinoid tumors, with one-year survival rates of approximately 81% for pancreatic and 83% for carcinoid patients, indicating potential efficacy and safety for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of sunitinib in patients with advanced neuroendocrine tumors. Kulke, MH., Lenz, HJ., Meropol, NJ., et al.[2022]

Surufatinib, a tyrosine kinase inhibitor, is well-absorbed in both rats and humans, with a median time to peak concentration of 4 hours after oral dosing, and a significantly longer half-life in humans (23.3 hours) compared to rats (3.12-6.48 hours).

The primary route of elimination for surufatinib in both species is fecal excretion, accounting for about 87% of the dose, indicating that the drug is largely eliminated unchanged, with no single metabolite making up more than 10% of the total radioactivity in circulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption, Metabolism and Excretion of Surufatinib in Rats and Humans. Li, K., Ma, S., Miao, L., et al.[2021]

In the KEYNOTE-028 study, pembrolizumab showed antitumor activity in patients with well-differentiated or moderately-differentiated neuroendocrine tumors (NETs), with objective response rates of 12% for carcinoid tumors and 6.3% for pancreatic NETs after a median follow-up of 20 to 21 months.

The treatment was generally well-tolerated, with 68% to 69% of patients experiencing treatment-related adverse events, the most common being diarrhea and fatigue, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of programmed death-ligand 1-positive advanced carcinoid or pancreatic neuroendocrine tumors: Results from the KEYNOTE-028 study. Mehnert, JM., Bergsland, E., O'Neil, BH., et al.[2021]

The review highlights the importance of somatostatin analogs and peptide receptor-targeted therapies in the treatment of neuroendocrine tumors, showcasing their efficacy in managing the disease.

It emphasizes the need for improved clinical trial designs and the development of biomarkers to better assess treatment outcomes and guide future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accomplishments in 2008 in the management of gastrointestinal neuroendocrine tumors. Kulke, MH., Scherübl, H.[2021]

In a study involving 242 patients with advanced neuroendocrine tumors treated with surufatinib, the presence of treatment-related adverse events (TRAEs) like hypertension, proteinuria, and hemorrhage in the first 4 weeks was linked to a longer progression-free survival (PFS) of 11.1 months compared to 9.2 months for those without these events.

The findings suggest that TRAEs could serve as potential biomarkers for predicting the efficacy of surufatinib treatment, indicating that patients experiencing these side effects may have better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events as predictive biomarkers of efficacy in patients with advanced neuroendocrine tumors treated with surufatinib: results from two phase III studies. Li, J., Cheng, Y., Bai, C., et al.[2022]

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Press Release - Exelixis, Inc.

Zanzalintinib in combination with nivolumab demonstrated an objective response rate of 63% and a disease control rate of 90%.

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