Trials / Recruiting

RecruitingNCT06498648

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

Status: Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 74 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. The primary objective of the phase 1 part of this trial is to define the schedule of sequential abemaciclib and gemcitabine and recommended phase 2 dose (RP2D) of retinoblastoma positive (Rb\[+ve\]) sarcomas. II. The primary objective of the phase 2 part of the trial is to define the progression-free survival (PFS) of sequential abemaciclib followed by gemcitabine at RP2D compared to the standard of care gemcitabine and docetaxel in advanced Rb(+ve) leiomyosarcomas and dedifferentiated liposarcomas. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity in phase 1. II. To determine cell cycle arrest and recovery with abemaciclib 200mg twice per day (BID) 5 to 7 days by blood thymidine kinase activity (Tka). III. To assess the toxicity profile of the sequential abemaciclib followed by gemcitabine treatment using Common Terminology Criteria for Adverse Events (CTCAE) version 5 in phase 1 \& phase 2. IV. To determine the preliminary objective response rate (ORR) by Response Criteria in Solid Tumors (RECIST)1.1 in phase 1. V. To compare overall survival (OS) of sequential abemaciclib followed by gemcitabine at RP2D to the standard of care gemcitabine and docetaxel in phase 2. VI. To compare the objective response rate (ORR) at time of best response by RECIST1.1 of sequential abemaciclib followed by gemcitabine at RP2D to the standard of care gemcitabine and docetaxel in phase 2. VII. To compare PFS and ORR after cross-over in each treatment arm. VIII. To identify mechanisms of resistance to sequential treatment through correlative studies of the cell cycle genes. OUTLINE: Patients in phase 1 part A are assigned to cohort 1 or 2. Patients in phase 2 are randomized to arm A or arm B and may cross over to the alternate arm after disease progression. PHASE 1 PART A: COHORT I: Patients receive abemaciclib orally (PO) twice per day (BID) on days 1-5 and 15-19 of each cycle and gemcitabine intravenously (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 computed tomography (CT) during screening and on study. Additionally, patients undergo blood sample collection during screening and on study. COHORT II: 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. PHASE 1 PART B: 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. PHASE 2: ARM A: 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 during screening and optionally on study. ARM B: 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. After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Conditions

Interventions

Type	Name	Description
DRUG	Abemaciclib	Given PO
PROCEDURE	Biopsy Procedure	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Docetaxel	Given IV
DRUG	Gemcitabine	Given IV

Timeline

Start date: 2026-03-18
Primary completion: 2027-01-31
Completion: 2027-01-31
First posted: 2024-07-12
Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06498648. Inclusion in this directory is not an endorsement.