SARC041: Study of Abemaciclib Versus Placebo in Patients With Advanced Dedifferentiated Liposarcoma

SARC041: Phase 3 Randomized Double-Blind Study of Abemaciclib Versus Placebo in Patients With Advanced Dedifferentiated Liposarcoma

This is a Phase 3 randomized double-blind study of abemaciclib versus placebo. Patients with progression of disease will cross over to open label abemaciclib.

Study Overview

• Status: Recruiting
• Conditions: Advanced Dedifferentiated Liposarcoma
• Intervention / Treatment: Drug: Abemaciclib; Drug: Placebo

Detailed Description

This is a phase 3, multicenter, randomized, double-blind, placebo-controlled study of patients with advanced, recurrent and/or metastatic DDLS.

Patients will be randomized 1:1 between abemaciclib and placebo and followed for disease progression. For those patients with progression of disease (by RECIST) on placebo, crossover to active drug will be offered to patients if they remain eligible for the clinical trial in all other respects. Unblinding and crossover is only allowed for radiographic progression (not clinical progression). Real-time radiology review by the treating physician will allow for rapid crossover for patients with progression on placebo. If patients are deemed to have disease that is too rapidly progressive to be considered for a randomized, double-blind, placebo-controlled clinical trial, they should be excluded from consideration.

• Study Type: Interventional
• Enrollment (Anticipated): 108
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: SARC Office; Phone Number: (734) 930-7600; Email: sarc@sarctrials.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Cancer Center, Anschutz Medical Campus
      • Contact: Natalie Frisbie; Phone Number: 720-848-0734; Email: Natalie.Frisbie@cuanschutz.edu
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Florida
      • Principal Investigator: Steven Attia, MD
      • Contact: Stacy Cuellar; Phone Number: 904-953-9476; Email: cuellar.yusneisy@mayo.edu
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Principal Investigator: Seth Pollack, MD
      • Contact: Briana Porwisz; Email: briana.porwisz@northwestern.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital Cancer Center
      • Principal Investigator: Edwin Choy, MD
      • Contact: Jannatun Nahar; Email: JNAHAR@mgh.harvard.edu
  • Missouri
    • Saint Louis, Missouri, United States, 63129
      • Recruiting
      • Washington University School of Medicine
      • Principal Investigator: Mia Weiss, MD
      • Contact: Kara Weekly; Phone Number: 314-273-6418; Email: kara.w@wustl.edu
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Tiffany Salcito; Email: salcitot@mskcc.org
      • Principal Investigator: Mark Dickson, MD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University
      • Principal Investigator: Richard Riedel, MD
      • Contact: Gloria Watkins; Email: gloria.watkins@duke.edu
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Principal Investigator: Lara Davis, MD
      • Contact: Amber Lee; Phone Number: 503-418-4488; Email: amber@ohsu.edu
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • University of Washington
      • Principal Investigator: Michael Wagner, MD
      • Contact: Eric Damiana; Phone Number: 206-606-8220; Email: edamiana@seattlecca.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Histologically confirmed diagnosis of dedifferentiated liposarcoma which is locally recurrent and/or metastatic. This study will accept the diagnosis made at the investigator's center.
• ECOG Performance Status of 0 or 1.
• At least one site of measurable disease on CT/MRI scan as defined by RECIST 1.1 criteria. Baseline imaging must be performed within 28 days of Day 1 of study.
• Adequate organ function
• The patient can swallow oral medications.
• Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization.
• Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout period of at least 21 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy).
• Written, voluntary informed consent
• Fertile men and women of childbearing potential must agree to use a highly effective method of birth control during the treatment period and for 3 weeks after last study drug administration in both sexes. Women of childbearing potential include pre-menopausal women and women within the first 2 years of the onset of menopause. Women of childbearing potential must have a negative pregnancy test ≤ seven days of the first dose of abemaciclib.
• Highly effective methods of birth control include an intrauterine device [IUD] or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection.
• Measurable disease and evidence of progression of disease as defined by RECIST 1.1 (including newly diagnosed disease, new disease sites in a patient who was previously NED, or a 20% growth of existing lesions within 6 months of registration).
• Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery within 3 months from completion of therapy to sites of CNS metastatic disease and are without evidence of clinical progression.

Exclusion Criteria:

• Patients with documentation of well-differentiated liposarcoma only are specifically excluded, owing to its characteristically slow growth. If high grade areas are suspected (dedifferentiation), but not proved by pathology analysis (e.g. after primary resection of a well-differentiated liposarcoma), a biopsy must be performed to demonstrate the high-grade dedifferentiated disease. If there is a question regarding the diagnosis, the PI should be consulted.
• Patients with bulky disease who urgently need cytotoxic chemotherapy (likely with doxorubicin + ifosfamide) will be excluded from this study. This is determined by the treating physician. If there is a question regarding the appropriateness of the patient for enrollment, the PI should be consulted.
• Prior systemic therapy with abemaciclib or any other selective CDK4 inhibitor (such as palbociclib)
• Concurrent, clinically significant, active malignancies within 12 months of study enrollment
• Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
• Major surgery within 3 weeks prior to Day 1 of study or who have not recovered adequately from prior surgery
• Patients with resectable for curative intent disease
• Patients that have GI absorption disorders that would impact the administration of oral abemaciclib.
• Women who are pregnant or nursing/breastfeeding.
• Known hypersensitivity to abemaciclib.
• Patients with untreated central nervous system disease.
• Inability to comply with protocol required procedures
• Patients currently taking the following drugs may interact with abemaciclib. Please refer to Section 5.2 of protocol.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• The patient has active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment.
• The patient has a 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.
• The patient has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to randomization, or is currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor not to be scientifically or medically compatible with this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abemaciclib; Abemaciclib will be administered 200mg orally twice a day. Each cycle is 28 days.	Drug: Abemaciclib; Abemaciclib will be administered 200mg orally twice a day. Each cycle is 28 days.; Other Names: LY2835219
Placebo Comparator: Placebo Arm; Patients will be randomized 1:1 and will receive placebo if they are randomized to the placebo arm of the study. Each cycle is 28 days.	Drug: Placebo; Placebo will be administered orally twice a day. Each cycle is 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the progression-free survival of patients treated with abemaciclib versus placebo	PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the objective response rate by RECIST 1.1	A patient will be deemed to have an objective response if they have a confirmed complete response or partial response as determined by RECIST v1.1	5 years
To determine PFS after crossover for patients initially randomized to placebo	PFS after crossover will only be determined for patients who were randomized to placebo. It will be measured from the start of abemaciclib treatment until the occurrence of disease progression or death due to any cause prior to documented disease progression.	5 years
To determine overall survival	The length of time from the start of treatment that patients diagnosed with sarcoma are still alive.	5 years

Collaborators and Investigators

• Sponsor: Sarcoma Alliance for Research through Collaboration
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Mark Dickson, MD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Anticipated): May 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (Actual): July 19, 2021

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Adipose Tissue; Liposarcoma
• Other Study ID Numbers: SARC041

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No