Testing the Addition of an Anti-cancer Drug, Abemaciclib, to the Usual Chemotherapy Treatment (Gemcitabine) for Soft Tissue Sarcoma
Phase I/II Study to Evaluate the Feasibility and Efficacy of Sequential Abemaciclib and Gemcitabine Treatment in Patients With Retinoblastoma (Rb)+ Sarcomas
3 other identifiers
interventional
74
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 10, 2024
CompletedFirst Posted
Study publicly available on registry
July 12, 2024
CompletedStudy Start
First participant enrolled
March 18, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2027
April 13, 2026
March 1, 2026
11 months
July 10, 2024
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Time course of blood thymidine kinase activity (TKa) (Phase 1 Part A)
Will be graphically evaluated: the change of blood TKa over time to facilitate a selection of regimen that has maximum decrease in blood TKa after end of abemaciclib (cell cycle arrest) and has maximum increase in blood TKa at time of gemcitabine injection. Descriptive statistics (mean, standard deviation) and graphical methods will be applied to examine the distribution of the data, error checking, and outlier identification. Since blood TKa and fluorothymidine F-18 (18F-FLT) positron emission tomography (PET) will be measured at baseline and multiple post treatment time points, if appropriate, linear mixed effect models for repeated measures analysis will be employed to assess its change over time. Appropriate transformation of the marker values will be used to satisfy the normality assumption of linear mixed effect model.
Baseline up to 2 years
Maximum tolerated dose (Phase I Part B)
Up to 28 days
Progression free survival (PFS) (phase II)
Will be estimated using the Kaplan-Meier method.
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
Secondary Outcomes (13)
Anti-tumor activity (phase I)
Up to 2 years
Cell cycle arrest (phase I)
At 5 to 7 days
Cell cycle recovery (phase I)
At 5 to 7 days
Incidence of adverse events (phase I)
Up to 2 years
Objective response rate (ORR) (phase I)
Up to 2 years
- +8 more secondary outcomes
Study Arms (5)
Phase 2 Arm A (abemaciclib, gemcitabine)
EXPERIMENTALPatients 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.
Phase 2 Arm B (gemcitabine, docetaxel)
ACTIVE COMPARATORPatients 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.
Phase I Part A Cohort I (abemaciclib, gemcitabine)
EXPERIMENTALPatients 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.
Phase I Part A Cohort II (abemaciclib, gemcitabine)
EXPERIMENTALPatients 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.
Phase I Part B (abemaciclib, gemcitabine)
EXPERIMENTALPatients 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
Given PO
Undergo tumor biopsy
Given IV
Undergo blood sample collection
Undergo CT
Given IV
Eligibility Criteria
You may qualify if:
- 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
- +8 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Elise F Nassif
University of Texas MD Anderson Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 10, 2024
First Posted
July 12, 2024
Study Start
March 18, 2026
Primary Completion (Estimated)
January 31, 2027
Study Completion (Estimated)
January 31, 2027
Last Updated
April 13, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.