Abemaciclib for Neuroendocrine Tumors

Not currently recruiting at 1 trial location

Overseen By David Zhen, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: Somatostatin analogs

Must not be taking: Telotristat, CDK4/6 inhibitors

Disqualifiers: Poorly differentiated NEC, MANECs, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of abemaciclib (also known as Verzenio, LY2835219, or Ramiven) in treating neuroendocrine tumors in the digestive system, particularly when these tumors have metastasized, resisted other treatments, and cannot be surgically removed. Abemaciclib blocks certain enzymes that promote tumor cell growth. The trial seeks participants whose tumors have progressed despite standard treatment within the past year. Participants should have inoperable tumors and have experienced disease progression. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you can continue using somatostatin analogs (SSAs) if the dose is stable for at least 2 months. Telotristat is not allowed.

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

Previous studies have used abemaciclib to treat various cancers, including breast cancer. Research has shown that most patients tolerate it well. Common side effects include diarrhea and fatigue, but adjusting the dose can often manage these. Importantly, no new safety issues have emerged, and serious side effects remain rare. This suggests that abemaciclib is safe based on its use in other conditions. However, as with any treatment, individual experiences may vary, and monitoring for side effects is crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for neuroendocrine tumors, which often rely on surgery, chemotherapy, or hormone therapy, Abemaciclib offers a different approach. This drug is a CDK4/6 inhibitor, which means it targets specific proteins involved in cell division, potentially slowing the growth of cancer cells. Researchers are excited because Abemaciclib is taken orally and has shown promise in other cancers, suggesting it might be effective with fewer side effects compared to more aggressive treatments. This unique mechanism of action could offer new hope for patients not responding to existing therapies.

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

Research has shown that abemaciclib effectively treats certain types of breast cancer. Studies have found that, when combined with hormone therapy, it significantly improves survival rates and helps prevent cancer from spreading. Abemaciclib blocks specific proteins that cancer cells require for growth, potentially slowing or stopping tumor growth. While it has proven successful in breast cancer, its effectiveness in treating neuroendocrine tumors remains under investigation in this trial. Early signs suggest it might work similarly for these tumors. ^{6 7 8 9 10}

Who Is on the Research Team?

David Zhen, M.D.

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults with advanced, treatment-resistant digestive system neuroendocrine tumors that can't be surgically removed. Participants must be able to take oral meds, have measurable disease by CT or MRI, and meet specific blood count and organ function criteria. Women of childbearing potential and men must agree to use effective contraception.

Inclusion Criteria

My cancer can be measured on scans according to specific criteria.

Your blood clotting tests should not be more than 1.5 times the upper limit of normal.

My cancer has spread and cannot be removed with surgery.

Exclusion Criteria

I do not have any severe illnesses that are not under control.

I have recovered from previous cancer treatment side effects, except for hair loss or mild nerve damage.

My kidneys are not working well (creatinine clearance < 30ml/min).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive abemaciclib orally twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 30 days and then every 4 months for up to 1 year.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib

Trial Overview The trial is testing the effectiveness of Abemaciclib in patients whose neuroendocrine tumors have spread and are not responding to other treatments. The drug aims to inhibit enzymes necessary for tumor cell growth.

How Is the Trial Designed?

Group I: Treatment (abemaciclib) Experimental Treatment 1 Intervention

Patients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

The combination of everolimus (RAD001) and octreotide LAR showed promising antitumor activity in patients with advanced neuroendocrine tumors, achieving a 20% response rate and a median progression-free survival of 60 weeks across 60 enrolled patients.

The treatment was well tolerated, with the most common side effect being mild aphthous ulceration, and significant reductions in tumor proliferation markers were observed, indicating a potential mechanism of action for the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. Yao, JC., Phan, AT., Chang, DZ., et al.[2023]

In a phase 3 study involving 429 patients with advanced neuroendocrine tumors, the combination of everolimus and octreotide LAR significantly improved progression-free survival, with a median of 16.4 months compared to 11.3 months for the placebo group.

Most adverse events related to the treatment were mild (grade 1 or 2), with common side effects including stomatitis, rash, fatigue, and diarrhea, indicating that the combination therapy is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Pavel, ME., Hainsworth, JD., Baudin, E., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38194616/

Results From a Preplanned monarchE Overall Survival ... Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in a significant improvement in invasive disease-free survival (IDFS) and ...

2. onclive.com onclive.com/view/adjuvant-abemaciclib-plus-endocrine-therapy-improves-os-in-high-risk-hr-her2-breast-cancer

Adjuvant Abemaciclib Plus Endocrine Therapy Improves ... Abemaciclib plus endocrine therapy significantly improves overall survival in high-risk, node-positive, hormone receptor-positive, HER2-negative ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0960977625006149

Metastatic Breast Cancer: A Propensity-Matched ... In this large, real-world cohort study, first-line abemaciclib was associated with a significant overall survival benefit compared to ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01994

Results From a Preplanned monarchE Overall Survival ... Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in a significant improvement in invasive disease-free survival (IDFS) and ...

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-expands-early-breast-cancer-indication-abemaciclib-endocrine-therapy

FDA expands early breast cancer indication for ... The major efficacy outcome measure was invasive disease-free survival (IDFS). A statistically significant difference was observed in the ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03155997

Study Details | NCT03155997 | Endocrine Therapy With or ... The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, ...

7. firstwordpharma.com firstwordpharma.com/story/6320946

Lilly to present new clinical data for Verzenio (abemaciclib ... Primary overall survival analysis from the Phase 3 monarchE study of Verzenio (abemaciclib) in HR+HER2-, node-positive, high-risk early ...

8. prnewswire.com prnewswire.com/news-releases/lillys-verzenio-abemaciclib-prolonged-survival-in-hr-her2--high-risk-early-breast-cancer-with-two-years-of-treatment-302586849.html

Lilly's Verzenio® (abemaciclib) prolonged survival in HR+, ... No new safety signals or delayed toxicities were observed. Adverse events were generally managed with dose modifications, consistent with prior ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11368096/

Practical Guidance on Abemaciclib in Combination with ... Efficacy and safety results by age in monarchE: adjuvant abemaciclib combined with endocrine therapy (ET) in patients with HR+, HER2-, node ...

10. curetoday.com curetoday.com/view/verzenio-plus-endocrine-therapy-benefits-survival-for-some-with-breast-cancer

Verzenio Plus Endocrine Therapy Benefits Survival for ... Verzenio plus endocrine therapy reduced death risk by 15.8% in high-risk early breast cancer patients compared to endocrine therapy alone. The ...