Abemaciclib for Liposarcoma

Not currently recruiting at 10 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of abemaciclib, a new oral medicine, for treating dedifferentiated liposarcoma, a type of cancer that has returned or spread. Participants will receive either abemaciclib or a placebo, a harmless pill resembling the real medicine. If the cancer worsens, patients can switch to abemaciclib. The trial seeks individuals diagnosed with dedifferentiated liposarcoma that has returned or spread and shows signs on a recent scan. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to help potentially bring a new treatment to market.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abemaciclib is generally safe for people. The FDA has already approved it to treat a type of breast cancer. In these patients, abemaciclib demonstrated good results with manageable side effects. Common side effects include diarrhea, tiredness, and nausea, but these are usually mild and treatable.

While specific safety information for abemaciclib in liposarcoma patients is lacking, its approval for other conditions provides a good understanding of its safety. Researchers understand how the drug works in the body and what side effects might occur.

Overall, abemaciclib appears to be a safe treatment option, with side effects that are usually mild and manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Abemaciclib is unique because it specifically targets CDK4 and CDK6 proteins, which are crucial for cancer cell division and growth. Unlike traditional chemotherapy that attacks all rapidly dividing cells, abemaciclib focuses on these proteins, potentially leading to fewer side effects. Researchers are excited about this treatment because it can be taken orally, offering a more convenient option compared to intravenous chemotherapy, and it might provide more personalized therapy for liposarcoma patients by directly interfering with the cancer's growth mechanism.

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

Research has shown that abemaciclib, which participants in this trial may receive, yields promising results in treating liposarcoma, a type of cancer. In earlier studies, patients who took abemaciclib lived for an average of 33 weeks without their cancer worsening. This indicates that many patients experienced a significant period where their cancer stopped growing. Additionally, 76.7% of patients did not see their cancer progress at 12 weeks. Abemaciclib is already approved for treating certain types of breast cancer, which increases confidence in its effectiveness. These findings suggest that abemaciclib could be a promising treatment option for people with liposarcoma. ^{2 6 7 8 9}

Who Is on the Research Team?

Mark Dickson, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

My cancer has grown or spread recently.

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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. 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% ...

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06498648?term=AREA%5BConditionSearch%5D(%22Liposarcoma%22)%20AND%20AREA%5BInterventionSearch%5D(%22Docetaxel%22)&rank=1

Testing the Addition of an Anti-cancer Drug, Abemaciclib, to ... 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: ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS11587

SARC041: A phase 3 randomized double-blind study of ... We hypothesize that treatment with abemaciclib will improve PFS compared to placebo in patients with recurrent or metastatic DDLS.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02846987

Study of Abemaciclib in Dedifferentiated Liposarcoma There are three types of violations: Failure to submit required clinical trial information; Submission of false or misleading clinical trial information ...

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

Clinical Review - Abemaciclib (Verzenio) - NCBI Bookshelf - NIH At the interim analysis 1 for OS (April 1, 2021), OS data were immature. There were 95 deaths (42 in the abemaciclib + ET arm and 53 in the ET arm) in ...

8. 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 ...

9. 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 ...