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

ConditionsAdvanced Dedifferentiated LiposarcomaAdvanced LeiomyosarcomaAdvanced Soft Tissue SarcomaMetastatic Dedifferentiated LiposarcomaMetastatic LeiomyosarcomaMetastatic Soft Tissue SarcomaStage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8Stage IV Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

Disqualifiers

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

Trial design

Design model

Sequential

Treatments tested in this trial

  • Abemaciclib

    Drug

    Given PO

  • Biopsy Procedure

    Procedure/Surgery

    Undergo tumor biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Docetaxel

    Drug

    Given IV

  • Gemcitabine

    Drug

    Given IV

Treatment groups

74 Participants
are divided into 5 treatment groups
Group A: Phase 2 Arm A (abemaciclib, gemcitabine)Experimental treatment 4 interventions
Group B: Phase 2 Arm B (gemcitabine, docetaxel)Active comparator 4 interventions
Group C: Phase I Part A Cohort I (abemaciclib, gemcitabine)Experimental treatment 4 interventions
Group D: Phase I Part A Cohort II (abemaciclib, gemcitabine)Experimental treatment 4 interventions
Group E: Phase I Part B (abemaciclib, gemcitabine)Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Baseline up to 2 years
2

Maximum tolerated dose (Phase I Part B)

Time frame
Up to 28 days
3

Progression free survival (PFS) (phase II)

Will be estimated using the Kaplan-Meier method.

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

Secondary outcomes

1

Anti-tumor activity (phase I)

Time frame
Up to 2 years
2

Cell cycle arrest (phase I)

Measured by blood TKa.

Time frame
At 5 to 7 days
3

Cell cycle recovery (phase I)

Measured by blood TKa.

Time frame
At 5 to 7 days
4

Incidence of adverse events (phase I)

Using Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Time frame
Up to 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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