Abemaciclib for Liposarcoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Investigational agents, CDK4 inhibitors

Disqualifiers: Active infection, Heart failure, 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: 12 weeks

33 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test any good and bad effects of the study drug called Abemaciclib. Abemaciclib could shrink your cancer but it could also cause side effects. Researchers hope to learn if the study drug will delay the growth of the cancer or shrink the cancer by at least one quarter compared to its present size. Abemaciclib is not FDA approved and has not been tested in liposarcoma, but it has shrunk tumors in patients with breast cancer, lymphoma, and lung cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have finished any previous systemic therapy at least 2-4 weeks before starting the trial. If you were on BCNU or mitomycin C, you need to have stopped those at least 6 weeks prior.

What data supports the effectiveness of the drug Abemaciclib for treating liposarcoma?

Research shows that drugs inhibiting CDK4/6, like Abemaciclib, can reduce the growth of liposarcoma cells, as CDK4 is often amplified in these tumors. This suggests that Abemaciclib might be effective in treating liposarcoma by targeting this specific pathway. ^{1 2 3 4 5}

How is the drug Abemaciclib unique in treating liposarcoma?

Abemaciclib is unique in treating liposarcoma because it targets CDK4/6, proteins that are often overactive in these tumors, potentially slowing their growth. This approach is different from traditional chemotherapy, which has limited effectiveness for liposarcoma. ^{1 5 6 7 8}

Research Team

Mark Dickson, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with a specific cancer called dedifferentiated liposarcoma, confirmed at MSKCC. Participants must have measurable disease progression recently and can have had any number of prior treatments, but not within the last 2-4 weeks (6 weeks for certain drugs). They should be in good physical condition (ECOG 0 or 1), not have other active cancers, and agree to use contraception. Those with stable treated brain metastasis may join.

Inclusion Criteria

My brain metastasis was treated and has been stable for 3 months.

I am fully active or can carry out light work.

I agree to use birth control and will not breastfeed while in the study.

Exclusion Criteria

I have recovered from previous treatment side effects to a mild level.

Patients receiving any other investigational agents

I have been treated with a CDK4 inhibitor before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib 200 mg bid to test its effects on dedifferentiated liposarcoma

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Abemaciclib

Trial Overview The study is testing Abemaciclib's effects on dedifferentiated liposarcoma. The drug has shown promise in shrinking tumors in breast cancer, lymphoma, and lung cancer patients but isn't FDA approved for liposarcoma yet. Researchers want to see if it can delay tumor growth or shrink tumors by at least one quarter.

Participant Groups

Group I: Abemaciclib (LY2835219) Experimental Treatment 1 Intervention

Patients will be treated with abemaciclib 200 mg bid.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

Erdafitinib, a pan-FGFR inhibitor, shows promise in treating dedifferentiated liposarcoma (DDLPS) by reducing cell viability and inducing apoptosis, particularly in tumors with high FGFR1 and/or FGFR4 expression, which correlates with poor prognosis.

Combining erdafitinib with the MDM2 antagonist RG7388 enhances its effectiveness, leading to improved tumor suppression in vitro and in vivo, and has shown disease stabilization in a patient with refractory DDLPS for 12 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting. Dadone-Montaudié, B., Laroche-Clary, A., Mongis, A., et al.[2020]

In a study of 61 patients with well-differentiated and dedifferentiated liposarcoma treated with palbociclib, the median progression-free survival was only 9.2 months for WDLPS and 2.6 months for DDLPS, indicating limited efficacy of the treatment.

Surgical outcomes showed that while some patients underwent successful resections after palbociclib treatment, there was no overall survival benefit, and the treatment did not significantly prolong tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world use of palbociclib monotherapy in retroperitoneal liposarcomas at a large volume sarcoma center. Nassif, EF., Cope, B., Traweek, R., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Regorafenib Versus Placebo in Advanced/Metastatic, Treatment-Refractory Liposarcoma: Results from the SARC024 Study. [2021]

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

Clinical and Molecular Spectrum of Liposarcoma. [2022]

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

FDA Approval Summary: Eribulin for Patients with Unresectable or Metastatic Liposarcoma Who Have Received a Prior Anthracycline-Containing Regimen. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting. [2020]

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

Antiproliferative effects of CDK4/6 inhibition in CDK4-amplified human liposarcoma in vitro and in vivo. [2020]

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

Adjuvant Palbociclib May be Associated with Delayed Recurrence in Completely Resected Retroperitoneal Liposarcoma: Results of a Single-Institution Retrospective Cohort Study. [2023]

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

Real-world use of palbociclib monotherapy in retroperitoneal liposarcomas at a large volume sarcoma center. [2023]

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

To Quiesce or Senesce, that is the question for Dedifferentiated Liposarcoma. [2023]