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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a drug called Abemaciclib (also known as Verzenio, LY2835219, or Ramiven) can help treat liposarcoma, a cancer affecting fat cells. The goal is to determine if the drug can halt cancer growth or significantly shrink it. This experimental treatment has shown promise in other cancers, such as breast cancer. Individuals with liposarcoma that cannot be surgically removed and have experienced recent cancer growth might be suitable for this study. Participants should be able to swallow pills and maintain stable health conditions aside from their cancer. As a Phase 2 trial, this study measures how well Abemaciclib works in an initial, smaller group of people, offering a chance to contribute to important research.

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.

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

Research has shown that Abemaciclib, the treatment under study, has potential in reducing tumors in various cancers, including breast cancer, lymphoma, and lung cancer. Abemaciclib is already FDA-approved for treating a specific type of breast cancer, indicating its general safety for patients.

In earlier studies, patients taking Abemaciclib experienced some side effects, but these were usually manageable. Common side effects included diarrhea, tiredness, and nausea. While these side effects are important to consider, they are not unusual for cancer treatments. The approval of Abemaciclib for other cancers provides some confidence in its safety, even though it has not been specifically tested for liposarcoma yet. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Abemaciclib is unique because it targets specific proteins called cyclin-dependent kinases (CDK4 and CDK6) that are involved in cell division and tumor growth. Unlike standard treatments for liposarcoma, which often include chemotherapy that affects all rapidly dividing cells, abemaciclib offers a more targeted approach, potentially reducing side effects. Researchers are excited about abemaciclib because it represents a novel way to slow down or stop the progression of liposarcoma, offering hope for more effective management of this challenging cancer.

What evidence suggests that Abemaciclib might be an effective treatment for liposarcoma?

Research has shown that Abemaciclib yields promising results in shrinking tumors in certain cancers, such as breast cancer. One study found it effective in treating dedifferentiated liposarcoma, with patients experiencing a median time of 33 weeks before their cancer began to grow again. For many patients, this meant the cancer stopped growing for a significant period. Additionally, 76.7% of patients did not see their cancer worsen for at least 12 weeks. Although the FDA has not yet approved Abemaciclib for liposarcoma, these early results suggest it could be beneficial in treating this type of cancer. Participants in this trial will receive Abemaciclib to further evaluate its effectiveness in treating liposarcoma. ^{1 2 3 6 7}

Who Is on the Research Team?

Mark Dickson, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

Citations

1. targetedonc.com targetedonc.com/view/abemaciclib-demonstrates-promising-clinical-activity-in-dedifferentiated-liposarcoma

Abemaciclib Demonstrates Promising Clinical Activity in ... Abemaciclib is approved by the FDA for the treatment of patients with HR-positive, HER2-negative metastatic breast cancer, and has demonstrated tumor shrinkage ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02846987

Study of Abemaciclib in Dedifferentiated Liposarcoma Most clinical studies have one primary outcome measure, but some have more than one. ... The main reason for the clinical trial. The types of primary purpose are: ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37695642/

Therapy-Induced Senescence Contributes to the Efficacy of ... The median progression-free survival was 33 weeks at the time of the data lock, with 23 of 30 progression-free at 12 weeks (76.7%, two-sided 95% ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601722/

Clinical Review - Abemaciclib (Verzenio) - NCBI Bookshelf - NIH As of the final primary outcome (IDFS) analysis (July 8, 2020), 97.9% of patients in the abemaciclib plus ET arm and 87.2% of patients in the ET arm ...

5. withpower.com withpower.com/trial/phase-3-liposarcoma-8-2021-3083f

Abemaciclib for Liposarcoma · Info for Participants In a study of 61 patients with well-differentiated and dedifferentiated liposarcoma treated with palbociclib, the median progression-free survival was only 9.2 ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.TPS11583

Phase I/II study to evaluate the feasibility and efficacy of ... Sequential administration of abemaciclib followed by gemcitabine enhances apoptosis, impairs DNA repair mechanisms, and induces sustained cell cycle arrest.

7. 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 ... The 36-month IDFS rate was 86.1% (95% CI, 82.8%-88.8%) with abemaciclib vs 79.0% (95% CI, 75.3%-82.3%) with endocrine therapy alone. The agency ...