Abemaciclib for Neuroendocrine Tumors

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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well abemaciclib works in treating patients with digestive system neuroendocrine tumors that have spread to other places in the body, do not respond to treatment, and cannot be removed by surgery. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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.

How is the drug Abemaciclib unique for treating neuroendocrine tumors?

Abemaciclib is unique because it is a CDK4/6 inhibitor, which means it targets specific proteins (CDK4 and CDK6) that help cancer cells grow and divide. This mechanism is different from other treatments like everolimus, which targets the mTOR pathway, offering a novel approach for treating neuroendocrine tumors. ^{1 2 3 4 5}

Research Team

David Zhen, M.D.

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. United States 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. [2023]

2. England 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Targeted inhibition of the WEE1 kinase as a novel therapeutic strategy in neuroendocrine neoplasms. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Everolimus with paclitaxel and carboplatin as first-line treatment for metastatic large-cell neuroendocrine lung carcinoma: a multicenter phase II trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Compassionate use of everolimus in a patient with a neuroendocrine tumor: a case report and discussion of the literature. [2019]