Abemaciclib for Sarcoma

Recruiting in Palo Alto (17 mi)

+4 other locations

Overseen by John Charlson, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Medical College of Wisconsin

Must not be taking: CDK inhibitors, CYP3A inducers

Disqualifiers: Liposarcoma, Uncontrolled illness, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

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.

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}

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.

Trial 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 (CDK4/6 Inhibitor)

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.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Dr. Joseph E. Kerschner

Medical College of Wisconsin

Chief Medical Officer since 2011

MD, specific institution not identified

Dr. John R. Raymond, Sr.

Medical College of Wisconsin

Chief Executive Officer since 2010

MD from the Medical University of South Carolina

Findings from Research

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]

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]

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]