Abemaciclib for Sarcoma

Recruiting at 4 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

Trial Summary

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.

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

Abemaciclib, a drug that blocks certain proteins (CDK4/6) involved in cell growth, has shown promise in treating other cancers like breast cancer and mesothelioma. Similar drugs targeting the same proteins have been studied for sarcomas, suggesting potential effectiveness. ^{1 2 3 4 5}

How is the drug Abemaciclib unique for treating sarcoma?

Abemaciclib is unique because it is a CDK4/6 inhibitor, which means it works by blocking specific proteins (CDK4 and CDK6) that help cancer cells grow and divide. This mechanism is different from many traditional chemotherapy treatments, which often target rapidly dividing cells in general. ^{2 3 6 7 8}

What is the purpose of this trial?

This trial tests Abemaciclib, a cancer medication taken by mouth, in patients with advanced soft tissue and bone sarcomas. The drug works by blocking proteins that help cancer cells grow and divide.

Research Team

John Charlson, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

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

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

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

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

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

Preclinical Evaluation of Vemurafenib as Therapy for BRAFV600E Mutated Sarcomas. [2018]

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

CDK4/6 Inhibition With Lerociclib is a Potential Therapeutic Strategy for the Treatment of Pediatric Sarcomas. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes Predict Progression-Free Survival of Patients with Advanced Breast Cancer Treated with Abemaciclib. [2022]

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

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. [2020]