Abemaciclib for Liposarcoma

Recruiting at 9 trial locations

Overseen By SARC Office

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sarcoma Alliance for Research through Collaboration

Must not be taking: CDK4 inhibitors

Disqualifiers: Active malignancies, Severe medical disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

108 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing abemaciclib, a drug that blocks proteins helping cancer cells grow, in patients with advanced or spreading DDLS. The goal is to see if it can stop the cancer from getting worse.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking drugs that may interact with abemaciclib, you should consult with the study team for guidance.

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

Research on similar drugs like LEE011, which also targets CDK4/6, shows that inhibiting these proteins can slow down the growth of liposarcoma cells. This suggests that Abemaciclib, which works in a similar way, might also be effective for this type of cancer. ^{1 2 3 4 5}

How does the drug Abemaciclib differ from other treatments for liposarcoma?

Abemaciclib is unique because it targets cyclin-dependent kinases 4 and 6 (CDK4/6), which are often amplified in liposarcoma, potentially inhibiting tumor growth by blocking cell cycle progression. This mechanism is different from traditional chemotherapy, which generally targets rapidly dividing cells without specific molecular targets. ^{1 2 3 6 7}

Research Team

Mark Dickson, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with advanced dedifferentiated liposarcoma, measurable disease progression, and an ECOG Performance Status of 0 or 1 can join. They must be able to swallow pills, have recovered from prior treatments, and use effective birth control. Excluded are those who need urgent chemotherapy, have had certain recent surgeries or therapies including CDK4 inhibitors like abemaciclib, severe concurrent diseases, resectable disease for cure intent, pregnancy/breastfeeding women, known hypersensitivity to abemaciclib or untreated central nervous system disease.

Inclusion Criteria

I can take pills by mouth.

If you're a woman of childbearing age, you must use a very effective form of birth control like an IUD or barrier method. If you choose condoms, you should also use a sperm-killing gel or cream for extra protection.

My cancer has grown or spread recently.

Exclusion Criteria

I do not have any stomach or intestine problems that affect how I absorb pills.

I do not have a slow-growing type of liposarcoma.

I have a history of serious heart conditions, including fainting due to heart issues, dangerous irregular heartbeats, or sudden cardiac arrest.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either abemaciclib or placebo, with each cycle lasting 28 days

5 years

Crossover

Patients with disease progression on placebo may cross over to receive abemaciclib

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Abemaciclib
• Placebo

Trial Overview This Phase 3 trial tests the drug Abemaciclib against a placebo in patients with advanced dedifferentiated liposarcoma. If their condition worsens on placebo they can switch to open-label Abemaciclib. The study is double-blind meaning neither participants nor researchers know who gets the real drug versus placebo until after the results.

Participant Groups

Group I: Abemaciclib Experimental Treatment 1 Intervention

Abemaciclib will be administered 200mg orally twice a day. Each cycle is 28 days.

Group II: Placebo Arm Placebo Group 1 Intervention

Patients will be randomized 1:1 and will receive placebo if they are randomized to the placebo arm of the study. Each cycle is 28 days.

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?

Sarcoma Alliance for Research through Collaboration

Lead Sponsor

Trials

26

Recruited

2,000+

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

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]

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

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

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

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

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

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

5. England pubmed.ncbi.nlm.nih.gov

Overview of systemic therapy options in liposarcoma, with a focus on the activity of selinexor, a selective inhibitor of nuclear export in dedifferentiated liposarcoma. [2022]

6. 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]

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

SRC inhibition represents a potential therapeutic strategy in liposarcoma. [2020]