Abemaciclib for Sarcoma

Recruiting at 5 trial locations

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must not be taking: CDK inhibitors, CYP3A inducers

Disqualifiers: Liposarcoma, Uncontrolled illness, 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

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Abemaciclib, a medication, to evaluate its effectiveness for individuals with certain types of serious sarcoma, a cancer affecting bones and soft tissues. Participants should have sarcoma that has spread or cannot be surgically removed and must have a specific protein (Rb) in their tumor. The trial targets those who have undergone some cancer treatments, but whose cancer continues to progress. Participants will take the medication twice daily until their condition changes or they need to stop for other reasons. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 21 days after the last chemotherapy dose and 14 days after the end of radiotherapy before enrollment. Additionally, you cannot be on strong CYP3A inducers or inhibitors during the trial.

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

Research has shown that abemaciclib has been tested in various situations and is generally well-tolerated. In one study, 97.9% of patients who took abemaciclib with hormone therapy experienced positive outcomes, indicating that most managed the drug well. Another study examined its use with other cancer drugs for Ewing's sarcoma, suggesting it is safe to combine with other treatments.

Although these studies did not specify side effects, the FDA's approval of abemaciclib for certain cancers supports its safety for humans, indicating thorough safety testing in other contexts. However, like any medication, some side effects may occur, but studies show that most patients tolerate abemaciclib well.

Prospective trial participants should discuss any concerns with the research team to understand how abemaciclib might affect them personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for sarcoma, which often involve chemotherapy, radiation, or surgery, Abemaciclib offers a unique approach by specifically targeting and inhibiting cyclin-dependent kinases 4 and 6 (CDK4/6). This mechanism disrupts the cancer cell cycle, potentially preventing tumor growth and proliferation. Researchers are excited about Abemaciclib because it provides a more targeted cancer treatment, which may lead to fewer side effects and improved outcomes for patients with sarcoma.

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

Research has shown that Abemaciclib may help treat certain cancers. In studies with breast cancer patients, combining Abemaciclib with hormone therapy extended their survival. This indicates that Abemaciclib can slow cancer growth. Although limited data exists on sarcoma, Abemaciclib stops cancer cells from dividing, which could be beneficial for treating sarcoma. Early results in similar cancers offer hope that it might be effective for sarcoma as well. Participants in this trial will receive Abemaciclib to evaluate its effectiveness specifically for sarcoma. ^{2 3 4 5 6}

Who Is on the Research Team?

John Charlson, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

Adults with certain types of advanced sarcomas (like osteosarcoma, chondrosarcoma) that can't be surgically removed and have specific CDK pathway changes. They should not have had prior treatment with CDK4/6 inhibitors, must show disease progression recently or be newly diagnosed, and their organs must function well. Women of childbearing potential need to use effective contraception.

Inclusion Criteria

All subjects must have measurable disease as defined by RECIST 1.1. (See RECIST 1.1 criteria in Appendix 10.

I am fully active or restricted in physically strenuous activity but can do light work.

It has been more than 14 days since my last radiotherapy session.

Exclusion Criteria

I have recovered from my last chemotherapy, except for possible hair loss or mild nerve pain.

I do not have any other cancer that needs treatment.

Pregnant women and women who are breast-feeding.

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 twice daily until progression or discontinuation criteria are met

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 trial is testing Abemaciclib, given orally at a dose of 200 mg twice daily to see if it's effective for patients with bone and soft tissue sarcomas that have alterations in the CDK pathway. It's a phase II study where all participants receive the same treatment until they no longer benefit from it.

How Is the Trial Designed?

Group I: Abemaciclib Experimental Treatment 1 Intervention

Subjects will be treated with abemaciclib 200 mg twice daily by mouth.

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?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

In phase III clinical trials (MONARCH 2 and MONARCH 3), abemaciclib, a CDK4 & 6 inhibitor, significantly improved progression-free survival and overall survival in women with hormone receptor positive (HR+) and HER2-negative advanced breast cancer when used in combination with endocrine therapy.

Abemaciclib demonstrated a tolerable safety profile, making it a promising treatment option for patients who have progressed after previous endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. Masuda, N., Saji, S., Kawaguchi, T., et al.[2021]

Abemaciclib is a potent oral CDK4 and CDK6 inhibitor that effectively treats hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, showing response rates between 19.7% and 59% in major clinical trials.

The drug is well-tolerated, with common side effects including diarrhea and neutropenia, and it offers the advantage of continuous dosing and potential use as a monotherapy, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. Palumbo, A., Lau, G., Saraceni, M.[2020]

In a study involving 900 patients treated with abemaciclib for advanced breast cancer, patient-reported outcomes (PROs) such as physical function and pain were found to be significant predictors of progression-free survival (PFS), indicating their importance in treatment outcomes.

Patients with low physical function experienced a reduced benefit from abemaciclib compared to those with intermediate or high physical function, highlighting the need to consider PROs as independent prognostic markers in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes Predict Progression-Free Survival of Patients with Advanced Breast Cancer Treated with Abemaciclib. Badaoui, S., Kichenadasse, G., Rowland, A., et al.[2022]

Vemurafenib showed a strong cytostatic effect in a liposarcoma cell line (SA-4) by causing cell cycle arrest, but required higher doses compared to its effects in melanoma cells, indicating a need for continuous treatment for sustained growth inhibition.

Overall, vemurafenib had limited effectiveness in other sarcoma cell lines with the BRAFV600E mutation, suggesting that it may not be a sufficient standalone therapy and highlighting the potential for exploring combination treatments with other drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of Vemurafenib as Therapy for BRAFV600E Mutated Sarcomas. Gouravan, S., Meza-Zepeda, LA., Myklebost, O., et al.[2018]

In a phase 1b study involving 50 patients with advanced non-small cell lung cancer (NSCLC), the combination of abemaciclib and pembrolizumab showed significant toxicity, with 80% of patients in cohort A and 76% in cohort B experiencing severe treatment-emergent adverse events.

Despite some antitumor activity, including a disease control rate of 56% in cohort A and 64% in cohort B, the overall risk-benefit profile of this combination therapy does not support further investigation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. Pujol, JL., Vansteenkiste, J., Paz-Ares Rodríguez, L., et al.[2022]

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

Abemaciclib has demonstrated promising clinical activity in patients with relapsed mesothelioma that is deficient in the p16ink4A protein, suggesting it may be an effective treatment option for this specific cancer type.

The findings indicate a potential new therapeutic avenue for mesothelioma patients, particularly those whose tumors lack the p16ink4A protein, which is often associated with tumor suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibition Shows Clinical Activity in p16ink4A-Deficient Mesothelioma. [2022]

Lerociclib, a CDK4/6 inhibitor, effectively induced cell cycle arrest and reduced the viability, proliferation, motility, and stemness of pediatric sarcoma cells in both traditional 2D cultures and 3D bioprinted tumors.

The study identified CDK4/6 and its intermediaries as key targets in sarcoma cell lines, suggesting that lerociclib could be a promising new treatment strategy for these diverse tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibition With Lerociclib is a Potential Therapeutic Strategy for the Treatment of Pediatric Sarcomas. Julson, JR., Horton, SC., Quinn, CH., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05440786?term=AREA%5BExpandedAccessNCTId%5DNCT03763604&rank=3

NCT05440786 | CAMPFIRE: A Study of Abemaciclib ... The purpose of this study is to measure the benefit of adding abemaciclib to chemotherapy (irinotecan and temozolamide) for Ewing's sarcoma that has come ...

2. 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 ...

3. firstwordpharma.com firstwordpharma.com/story/6320946

Lilly to present new clinical data for Verzenio (abemaciclib ... In a mini oral presentation, Lilly will share updated results from the FORAGER-1 study, a first-in-human Phase 1 study of vepugratinib ( ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12513154/

Prevalence and prognosis of patients with breast cancer ... Nationwide studies on the prevalence, characteristics and long-term prognosis of patients with early breast cancer and a potential ...

5. 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 ... Abemaciclib plus endocrine therapy significantly improves overall survival in high-risk, node-positive, hormone receptor-positive, HER2-negative ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04238819

NCT04238819 | A Study of Abemaciclib (LY2835219) in ... The study's purpose is to see if the drug, abemaciclib, is safe and effective when given with other drugs to kill cancer cells.