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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04967521
Recruitment Status : Not yet recruiting
First Posted : July 19, 2021
Last Update Posted : July 27, 2021
Eli Lilly and Company
Information provided by (Responsible Party):
Sarcoma Alliance for Research through Collaboration

Tracking Information
First Submitted Date  ICMJE July 8, 2021
First Posted Date  ICMJE July 19, 2021
Last Update Posted Date July 27, 2021
Estimated Study Start Date  ICMJE September 2021
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2021)
To determine the progression-free survival of patients treated with abemaciclib versus placebo [ Time Frame: 5 years ]
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2021)
  • To determine the objective response rate by RECIST 1.1 [ Time Frame: 5 years ]
    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
  • To determine PFS after crossover for patients initially randomized to placebo [ Time Frame: 5 years ]
    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.
  • To determine overall survival [ Time Frame: 5 years ]
    The length of time from the start of treatment that patients diagnosed with sarcoma are still alive.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE SARC041: Study of Abemaciclib Versus Placebo in Patients With Advanced Dedifferentiated Liposarcoma
Official Title  ICMJE SARC041: Phase 3 Randomized Double-Blind Study of Abemaciclib Versus Placebo in Patients With Advanced Dedifferentiated Liposarcoma
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Advanced Dedifferentiated Liposarcoma
Intervention  ICMJE
  • Drug: Abemaciclib
    Abemaciclib will be administered 200mg orally twice a day. Each cycle is 28 days.
    Other Name: LY2835219
  • Drug: Placebo
    Placebo will be administered orally twice a day. Each cycle is 28 days.
Study Arms  ICMJE
  • Experimental: Abemaciclib
    Abemaciclib will be administered 200mg orally twice a day. Each cycle is 28 days.
    Intervention: Drug: Abemaciclib
  • 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.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: July 8, 2021)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2024
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: SARC Office (734) 930-7600
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT04967521
Other Study ID Numbers  ICMJE SARC041
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sarcoma Alliance for Research through Collaboration
Study Sponsor  ICMJE Sarcoma Alliance for Research through Collaboration
Collaborators  ICMJE Eli Lilly and Company
Investigators  ICMJE
Principal Investigator: Mark Dickson, MD Memorial Sloan Kettering Cancer Center
PRS Account Sarcoma Alliance for Research through Collaboration
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP