Testing the Addition of an Anti-cancer Drug, Abemaciclib, to the Usual Chemotherapy Treatment (Gemcitabine) for Soft Tissue Sarcoma
NCT Number: NCT06498648
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Advanced Soft Tissue Sarcoma|Dedifferentiated Liposarcoma|Leiomyosarcoma|Metastatic Soft Tissue Sarcoma|Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8|Stage IV Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
Interventions: DRUG: Abemaciclib|PROCEDURE: Biopsy|PROCEDURE: Biospecimen Collection|DRUG: Docetaxel|OTHER: Fluorothymidine F-18|DRUG: Gemcitabine|PROCEDURE: Positron Emission Tomography
Sponsor: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 70
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-30
Completion Date: 2026-10-01

Summary:
This phase 1/2 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 DNA 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.

Primary Outcome Measures: 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 \[18\]F-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 (MTD) (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 Outcome Measures: Anti-tumor activity (phase I), Up to 2 years|Cell cycle arrest (phase I), Measured by blood thymidine kinase activity (TKa), At 5 to 7 days|Cell cycle recovery (phase I), Measured by blood TKa., At 5 to 7 days|Incidence of adverse events (phase I), Using Common Terminology Criteria for Adverse Events (CTCAE) version 5., Up to 2 years|Objective response rate (ORR) (phase I), By Response Criteria in Solid Tumors 1.1 with a 95% exact CI will be provided., Up to 2 years|Overall survival (phase II), Respective point estimates will be provided along with 95% confidence interval (CI) by treatment arms and then by histologic groups within treatment arm. The hazard ratio along with 95% CI using Cox proportional hazard models will be estimated. Will be estimated using the Kaplan-Meier method., From randomization to death, up to 2 years|ORR at time of best response (phase II), A 95% exact CI will be provided., Up to 2 years|Incidence of adverse events (phase II), Assessed by CTCAE v5., Up to 2 years|Cell cycle arrest (phase II), Measured by blood TKa., At day 5-7|Cell cycle recovery (phase II), Measured by blood TKa., At day 5-7|Mechanisms of resistance to sequential treatment (phase II), Up to 2 years|PFS after crossover, Will be estimated using the Kaplan-Meier method., From randomization to either disease progression as defined by RECIST or death from any cause, up to 2 years|ORR after crossover, A 95% exact CI will be provided., Up to 2 years
Other Outcome Measures: Cell cycle arrest, By fluorothymidine F-18 (18F-FLT) positron emission tomography (PET) and its associations with blood TKa., From baseline to gemcitabine|Cell cycle recovery, By 18F-FLT PET and its associations with blood TKa., From baseline to gemcitabine