Recruiting

Phase 1

Phase 2

Abemaciclib & GemcitabineTesting the Addition of an Anti-cancer Drug, Abemaciclib, to the Usual Chemotherapy Treatment (Gemcitabine) for Soft Tissue Sarcoma

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06498648

Conditions

Advanced Dedifferentiated Liposarcoma

Advanced Leiomyosarcoma

Advanced Soft Tissue Sarcoma

Metastatic Dedifferentiated Liposarcoma

Metastatic Leiomyosarcoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Abemaciclib

Biopsy Procedure

Biospecimen Collection

Computed Tomography

Docetaxel

Study Details

Brief summary:

This phase I/II trial tests the side effects and best dose of abemaciclib when added to gemcitabine and compares the effectiveness of that treatment to the usual treatment of gemcitabine with docetaxel for the treatment of patients with soft tissue sarcoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) (phase 1) or patients with leiomyosarcoma or dedifferentiated liposarcoma (phase 2). Abemaciclib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops cancer cells from growing and dividing and may kill them. Giving abemaciclib with gemcitabine may be safe and effective when compared to treatment with gemcitabine and docetaxel for patients with advanced or metastatic soft tissue sarcoma or leiomyosarcoma or dedifferentiated liposarcoma.

Conditions

Advanced Dedifferentiated Liposarcoma

Advanced Leiomyosarcoma

Advanced Soft Tissue Sarcoma

Metastatic Dedifferentiated Liposarcoma

Metastatic Leiomyosarcoma

Study ID

NCT06498648

Start date

Mar 18, 2026

Status verified date

Mar, 2026

Completion date

Jan 31, 2027

Anticipated

Primary completion date

Jan 31, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Phase 1: Patients must have advanced/metastatic histologically confirmed soft tissue sarcoma and have received at least one prior standard systemic therapy (prior gemcitabine is allowed)
Phase 2: Patients must have advanced/metastatic pathologically confirmed leiomyosarcoma or dedifferentiated liposarcoma for which gemcitabine and docetaxel is considered standard-of-care, patients may be systemic-treatment naïve. Prior gemcitabine is not allowed
Patients must have presence of measurable/assessable tumor
Patients must have intact Rb gene expression in the baseline tumor biopsy or archived tumor sample, as assessed by immunohistochemistry (at MD Anderson: clone G3- 245, BD Pharmagen, RRID:AB\_385259, Clinical Laboratory Improvement Act \[CLIA\] certified antibody)
Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of abemaciclib in combination with gemcitabine in patients < 18 years of age, children are excluded from this study
Eastern Cooperative oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
Absolute neutrophil count ˃ 1.2K/µL
Hemoglobin ˃ 9.0 g/dL
Platelets ˃ 100K/mm\^3
Glomerular filtration rate (GFR) ≥ 60 mL/min unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min
Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), patient with Gilbert's syndrome ≤ 2.0 times ULN, or direct bilirubin within normal limits
Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 1.5 × institutional ULN
Alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 1.5 × institutional ULN
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association (NYHA) Functional Classification. To be eligible for this trial, patients should be class congestive heart failure (CHF) II or better
Patients must have a life expectancy of greater than 6 months
Females of childbearing potential must have a negative serum pregnancy test within one week of trial enrollment and be willing to use an adequate method of contraception to avoid pregnancy throughout the trial and for up to 6 months after the last dose of drug therapy. The effects of abemaciclib on the developing human fetus are unknown. For this reason and because CDK 4/6 inhibiting agents as well as gemcitabine are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of abemaciclib administration. Abstinence is considered an effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study ranging from three weeks prior to initiation of treatment and up to 6 months after the last dose of treatment
Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Patient is capable of swallowing oral medications

Exclusion Criteria:

Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
Patients who are receiving any other investigational agents. There must be no investigational drug use within 30 days or 5 half-lives of receiving the first dose of treatment on this treatment
History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib or gemcitabine
Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
Pregnant women are excluded from this study because abemaciclib is a CDK4/6 inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with abemaciclib or gemcitabine, breastfeeding should be discontinued if the mother is treated with abemaciclib or gemcitabine
Use of strong CYP34A inhibitors which cannot be discontinued by the patient prior to trial initiation. The washout period of these drugs should be 5 half-lives
Progression on prior CDK4 inhibitor therapy
Phase 2 only: Prior gemcitabine-based chemotherapy
Presence of significant cardiac disease. Significant cardiac disease includes 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
Patients with interstitial lung disease (ILD)
Patients with gastrointestinal conditions that may affect the absorption of oral medications
Patients must not have received or be scheduled to receive radiation therapy within 7 days or less from gemcitabine administration
Patients must not have had major surgery within 14 days prior to randomization

Study Design

Enrollment

74 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 2 Arm A (abemaciclib, gemcitabine)

Patients receive abemaciclib PO BID and gemcitabine IV on the schedule determined in phase 1 of the trial. Cycles repeat every 21 or 28 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients may cross over to arm B. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study.

active comparator: Phase 2 Arm B (gemcitabine, docetaxel)

Patients receive gemcitabine IV over 90 minutes on days 1 and 8 of each cycle and docetaxel IV over 60 minutes on day 8 of each cycle. Cycles repeat every 21 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity. At the time of disease progression, patients may cross over to arm A. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy during screening and optionally on study.

experimental: Phase I Part A Cohort I (abemaciclib, gemcitabine)

Patients receive abemaciclib PO BID on days 1-5 and 15-19 of each cycle and gemcitabine IV over 90 minutes on days 8 and 22 of each cycle. Cycles repeat every 28 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity. Patients may change to Phase 1 Part B treatment once the recommended schedule is determined. Patients also undergo CT during screening and on study. Additionally, patients undergo blood sample collection during screening and on study.

experimental: Phase I Part A Cohort II (abemaciclib, gemcitabine)

Patients receive abemaciclib PO BID on days 1-7 and gemcitabine IV over 90 minutes on day 10 of each cycle. Cycles repeat every 21 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity. Patients may change to Phase 1 Part B treatment once the recommended schedule is determined. Patients also undergo CT during screening and on study. Additionally, patients undergo blood sample collection during screening and on study.

experimental: Phase I Part B (abemaciclib, gemcitabine)

Patients receive the selected treatment schedule, Cohort 1 or Cohort 2, as above. Cycles repeat every 21 or 28 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity.

Interventions

Abemaciclib

Given PO

Biopsy Procedure

Undergo tumor biopsy

Biospecimen Collection

Undergo blood sample collection

Computed Tomography

Undergo CT

Docetaxel

Given IV

Gemcitabine

Given IV

Primary outcome measure

Time course of blood thymidine kinase activity (TKa) (Phase 1 Part A) [ Time Frame: Baseline up to 2 years ]
Maximum tolerated dose (Phase I Part B) [ Time Frame: Up to 28 days ]
Progression free survival (PFS) (phase II) [ Time Frame: From randomization to either disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) or death from any cause, up to 2 years ]

Central Contacts and Locations

Locations

UT MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Site Public Contact

866-632-6789 askmdanderson@mdanderson.org

Principal Investigator:

Elise F. Nassif

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Jun 17, 2026

Last verified

Mar, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-06-17.