Abemaciclib for Bone and Soft Tissue Sarcoma With Cyclin-Dependent Kinase (CDK) Pathway Alteration

Recruiting now · Phase 2

Conditions studied: Chondrosarcoma, Osteosarcoma, Soft Tissue Sarcoma

In brief

This is a single-arm, phase II study that will enroll a total of 45 subjects. All subjects will have a confirmed diagnosis of metastatic or unresectable soft tissue sarcoma or bone sarcoma. All subjects must have intact Rb, identified at the time of screening, by immunohistochemistry testing of submitted tumor specimen. Subjects will receive Abemaciclib 200 mg twice daily until progression or discontinuation criteria are met.

Key facts

Study ID

NCT04040205

Run by

Medical College of Wisconsin

People needed

44

Starts

2019-10-07

Expected to finish

2027-06-01

Last updated by the study team

2026-07-28

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Diagnosis of soft tissue sarcoma or conventional chondrosarcoma, dedifferentiated chondrosarcoma, chordoma, or osteosarcoma (see exclusion criteria below)
• Metastatic or locally advanced disease that is unresectable
• There is no limit to the number of prior therapies a subject may have had, but the following requirements must be met:
• Conventional chondrosarcoma low-grade osteosarcoma, and chordoma: No requirements regarding prior therapy
• Osteosarcoma (high-grade), Dedifferentiated chondrosarcoma: at least 1 prior anthracycline chemotherapy, alone or in combination, required either as adjuvant, neoadjuvant or in the metastatic setting. If anthracycline chemotherapy is contraindicated, alternative prior first line chemotherapy is acceptable.
• Soft tissue sarcoma: at least 1 line of systemic therapy, unless the sarcoma subtype is one that is generally considered unresponsive to standard chemotherapy.
• Age ≥ 18 years.
• Provide study specific (step 1) informed consent prior to study entry
• Documented CDK pathway abnormality on a commercially available mutation profiling test (Foundation, Tempus xT, etc), if performed previously as part of routine/standard care on tumor (metastatic or primary), having at least one of the following (a and/or b)
• Cyclin D1 (CCND1), cyclin D2 (CCND2), cyclin D3 (CCND3), cyclin dependent kinase 4 (CDK4), and/or cyclin dependent kinase 6 (CDK6) amplification/copy number gain
• Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) or CDKN2B copy number loss
• Provide study-specific (step 2) informed consent
• Rb positive confirmed by immunohistochemistry testing of archived tumor tissue specimen (metastatic or primary site) performed centrally at Medical College of Wisconsin Precision Medicine Laboratory.
• All subjects must have measurable disease as defined by RECIST 1.1. (See RECIST 1.1 criteria in Appendix 10.
• Subjects must also have had evidence of disease progression by RECIST 1.1 within 6 months of enrollment, or newly diagnosed within the last 6 months (refer to step 1 criteria regarding previous lines of therapy).
• A washout period of at least 21 days is required between last chemotherapy dose and enrollment.
• A washout period of at least 14 days is required between end of radiotherapy and enrollment.
• At least 14 days after surgery, and absence of significant wound healing issues that would pose infection risk.
• Subjects with brain metastasis that have been treated with definitive surgery or radiation and have been clinically stable for 3 months are eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate organ and marrow function as defined below (ULN indicates institutional upper limit of normal):
• Hemoglobin ≥ 8.0 g/dL
• a. Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Platelets ≥ 100 x 10\^9/L
• Total bilirubin ≤ 1.5 x ULN

You may not qualify if…

• Diagnosis of well differentiated (WD) or dedifferentiated (DD) liposarcoma
• Prior treatment with a specific CDK 4 or CDK 6 inhibitor - (such as palbociclib, abemaciclib, or ribociclib).
• Subjects who have not recovered (Common Terminology Criteria for Adverse Events [CTCAE v5.0] Grade ≤1) from the acute effects of chemotherapy (except for residual alopecia or Grade 2 peripheral neuropathy) prior to enrollment, or other toxicity or serious preexisting medical condition(s) (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea) that in the opinion of the site PI is expected to preclude participation in this study.
• Subjects currently receiving any other investigational agents.
• Current ongoing treatment with strong Cytochrome P450, family 3, subfamily A (CYP3A) inducers or inhibitors.
• Uncontrolled intercurrent illness including, but not limited to, known ongoing or active bacterial infection (requiring IV antibiotics), fungal infection, detectable viral infection (such as known HIV or active hepatitis B or C) (screening tests is not required for enrollment), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (specifically, atrial fibrillation or ventricular dysrhythmias except ventricular premature contractions), or psychiatric illness/social situations that would limit compliance with study requirements.
• The subject has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Pregnant women and women who are breast-feeding.
• Subjects must not have current evidence of another malignancy that requires treatment.
• Subjects who received treatment with live attenuated viruses within 30 days prior to eligibility confirmation or might receive the treatment through the duration of the trial.

Where it is running

• Mayo Clinic — Jacksonville, Florida, United States (enrolling)
• University of Iowa Hospitals and Clinics — Iowa City, Iowa, United States (enrolling)
• Washington University in St. Louis — St Louis, Missouri, United States (enrolling)
• Froedtert Hospital & the Medical College of Wisconsin — Milwaukee, Wisconsin, United States (enrolling)

Full record on ClinicalTrials.gov

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