Cabozantinib for Neuroendocrine Cancer

Recruiting at 1 trial location

Overseen By Nikolaos Trikalinos

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Anticoagulants, Kinase inhibitors

Disqualifiers: Other malignancy, Brain metastases, GI disorders, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests cabozantinib (Cabometyx) to determine its effectiveness in treating high-grade neuroendocrine cancer, particularly after other treatments have failed. These cancers often recur after initial therapies, making the search for better options crucial. Participants should have a high-grade neuroendocrine tumor that has progressed after at least one prior treatment, excluding small cell lung cancer. Those with such a cancer seeking new treatment options might find this trial suitable. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering a promising opportunity for those seeking new options.

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 blood thinners like warfarin, and you must not have taken any small molecule kinase inhibitors or other systemic anticancer therapies within a few weeks before starting the trial.

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

Research has shown that the FDA has approved cabozantinib for treating certain advanced neuroendocrine tumors, indicating its effectiveness and safety for these cancers. However, some studies found that many patients experienced serious side effects. About 62-65% of patients reported severe side effects, compared to 23-27% who took a placebo. While the treatment can be beneficial, there is a chance of experiencing strong side effects. Considering these potential risks alongside the benefits is important when deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neuroendocrine cancer?

Cabozantinib is unique because it targets multiple pathways involved in tumor growth and spread, particularly the MET, VEGFR, and RET pathways. Unlike standard treatments for neuroendocrine cancer, which often focus on just one of these pathways, cabozantinib's multi-target approach could potentially hinder cancer progression more effectively. Researchers are excited about cabozantinib because it may offer a broader attack on cancer cells, possibly leading to better outcomes for patients with this challenging condition.

What evidence suggests that Cabozantinib might be an effective treatment for neuroendocrine cancer?

Research has shown that cabozantinib, which participants in this trial will receive, may help treat neuroendocrine tumors. One study found that patients with pancreatic neuroendocrine tumors lived without disease progression for an average of 13.8 months while taking cabozantinib. Another study reported that the drug reduced the risk of disease progression or death by 77% compared to a placebo. For those with advanced lung or thymic neuroendocrine tumors, cabozantinib lowered this risk by 81%. These findings suggest that cabozantinib could be an effective treatment for serious neuroendocrine cancers, offering a potential option where few exist. ^{6 7 8 9 10}

Who Is on the Research Team?

Nikolaos Trikalinos

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Adults with high-grade neuroendocrine tumors that have worsened after first-line therapy can join this trial. They must not have small cell lung cancer, be in good physical condition, and agree to use contraception. Pregnant or breastfeeding women, those who've had cabozantinib before, recent major surgery or other cancer treatments are excluded.

Inclusion Criteria

My high-grade neuroendocrine tumor has worsened after treatment, but it's not small cell lung cancer.

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

I have recovered from side effects of previous treatments.

Exclusion Criteria

I have not had major surgery recently.

Currently receiving any other investigational agents

Pregnant and/or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cabozantinib 60 mg by mouth daily on days 1-21

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib

Trial Overview The trial tests Cabozantinib's effectiveness on neuroendocrine tumors. Participants will also undergo tissue biopsies and blood tests for biomarkers. The goal is to find better treatment options since current second- and third-line therapies lack consensus.

How Is the Trial Designed?

Group I: Cabozantinib Experimental Treatment 3 Interventions

-Cabozantinib 60 mg by mouth daily on days 1-21

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

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 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]

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]

Sunitinib has been shown to significantly improve progression-free survival in patients with unresectable, advanced, or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), making it the first targeted therapy approved for this condition.

Ongoing trials are exploring other promising treatments, including multitargeted tyrosine kinase inhibitors and monoclonal antibodies, which may further enhance therapeutic options for GEP-NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy innovations: tyrosine kinase inhibitors for the treatment of pancreatic neuroendocrine tumors. Raymond, E., Hobday, T., Castellano, D., et al.[2022]

Cabozantinib (CAB) demonstrated significant antitumor activity against neuroendocrine tumors (NETs) in both in vitro cell cultures and in vivo models, showing a dose-dependent effect on cell viability and proliferation.

CAB not only inhibited cell growth but also halted cell cycle progression and significantly reduced NET-induced angiogenesis and cell migration in a zebrafish model, suggesting its potential as an effective treatment for NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib in neuroendocrine tumors: tackling drug activity and resistance mechanisms. Cella, CA., Cazzoli, R., Fazio, N., et al.[2023]

Neuroendocrine tumors, which make up 1-2% of all cancers, can be slow-growing but may also be aggressive, with a high likelihood of metastasis to the liver, impacting survival rates significantly.

Current treatment options include somatostatin analogues, chemotherapy, and emerging targeted therapies like everolimus and sunitinib, with ongoing clinical trials exploring new strategies to improve outcomes for patients with advanced neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic treatment of neuroendocrine tumors with hepatic metastases. Demirkan, BH., Eriksson, B.[2019]

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]

The LOLA trial is the first prospective phase II study evaluating the safety and efficacy of cabozantinib combined with lanreotide in patients with advanced well-differentiated neuroendocrine tumors (NETs), aiming to enroll up to 69 participants over 42 months.

Cabozantinib targets key pathways in NET pathogenesis, and the trial will assess its optimal dosing and safety profile, with a focus on overall response rate and potential biomarkers, which could provide valuable insights for treating these rare tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the safety and activity of cabozantinib combined with lanreotide in gastroenteropancreatic and thoracic neuroendocrine tumors: rationale and protocol of the phase II LOLA trial. Corti, F., Brizzi, MP., Amoroso, V., et al.[2023]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39282913/

Phase 3 Trial of Cabozantinib to Treat Advanced ... - PubMed In the cohort of 95 patients with pancreatic neuroendocrine tumors, the median progression-free survival with cabozantinib was 13.8 months, as ...

2. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-results-subgroup-analysis-cabinet-phase-3

Press Release - Exelixis CABOMETYX reduced the risk of disease progression or death by 81% versus placebo in patients with advanced lung or thymic neuroendocrine ...

3. ipsen.com ipsen.com/press-releases/final-results-from-cabinet-phase-iii-trial-reinforce-efficacy-benefits-of-cabometyx-in-advanced-neuroendocrine-tumors-2946663/

Final results from CABINET Phase III trial reinforce efficacy ... These data demonstrated a statistically significant reduction in the risk of disease progression or death for Cabometyx versus placebo of 77% ( ...

4. netrf.org netrf.org/2024/10/22/cabozantinib-extends-progression-free-survival-in-phase-3-clinical-trial/

Cabozantinib Extends Progression-Free Survival in Phase ... The investigational drug cabozantinib (CABOMETYX®) has significantly improved outcomes for those living with advanced neuroendocrine tumors (NETs).

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2403991?outputType=chromeless

Phase 3 Trial of Cabozantinib to Treat Advanced ... In the cohort of 203 patients with extrapancreatic neuroendocrine tumors, the median progression-free survival with cabozantinib was 8.4 months, ...

6. cabometyx.com cabometyx.com/neuroendocrine-tumors

Neuroendocrine Tumors (NETs) | CABOMETYX® (cabozantinib) CABOMETYX is approved to treat certain people with advanced neuroendocrine tumors (NETs). See indication and important safety information.

7. cabometyxhcp.com cabometyxhcp.com/

CABOMETYX® (cabozantinib) HCP | See Approved Indications CABOMETYX® (cabozantinib) is a multi-indication cancer treatment FDA-approved for 1L & 2L aRCC, 2L HCC and 2L DTC. See Important Safety Information.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11821447/

Phase 3 Trial of Cabozantinib in Advanced Neuroendocrine ... Grade 3 or higher adverse events were noted in 62–65% of patients treated with cabozantinib compared to 23–27% with placebo. Common grade 3 or ...

9. cabometyxhcp.com cabometyxhcp.com/net-treatment/cabinet-data/pnet-efficacy

Previously treated pNET efficacy data CABOMETYX quadrupled median PFS in pNET 1. 78% reduction in risk of progression or death. PFS results in pNET patients across select disease characteristics.

10. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-us-fda-approval-cabometyxr-cabozantinib-4

Exelixis Announces U.S. FDA Approval of CABOMETYX ... CABOMETYX is now the first and only systemic treatment that is FDA approved for previously treated neuroendocrine tumors regardless of primary tumor site, ...