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A Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well/Dedifferentiated Liposarcoma

Primary Purpose

Liposarcomas, Dedifferentiated, Liposarcoma - Well Differentiated, Liposarcoma; Mixed Type

Status
Unknown status
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
Ribociclib
Sponsored by
Assaf-Harofeh Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liposarcomas, Dedifferentiated focused on measuring CDK4 inhibitor, LEE011, ribociclib, liposarcoma dedifferentiated, liposarcoma well differentiated

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Written informed consent
  • Age ≥ 18 years
  • Histological confirmed diagnosis of WDL/DDL with metastatic or locally advanced disease not amenable to complete resection
  • WDL/DDL patients must have documentation of disease progression within 6 months prior to study entry
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Measurable disease by RECIST v1.1 criteria. At least one measurable lesion located outside of a previously irradiated area
  • Formalin fixed paraffin embedded tumor blocs and representative hematoxylin/eosin slides (preferably both) should be provided for immunohistochemistry staining and molecular analysis of 50 gene signature panel and must have increased CDK4 gene copy number (at least >/=3) and proficient Rb gene
  • Patient has adequate bone marrow and organ function
  • Must be able to swallow ribociclib capsules/tablets

Exclusion Criteria:

  • A known hypersensitivity to ribociclib or any of its excipients
  • A concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer
  • Patients with central nervous system (CNS) involvement at least 4 weeks from prior therapy completion
  • Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening)
  • On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF >450 msec
  • Participation in a prior investigational study within 30 days prior to enrollment
  • Patient has had major surgery within 14 days prior to starting study drug

Sites / Locations

  • Assaf Harofeh Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ribociclib

Arm Description

Oral, ribociclib 600 mg x 1 a day, 21 days on 7 days off

Outcomes

Primary Outcome Measures

Response to therapy as evaluated by RECIST 1.1
Response to therapy as evaluated by Choi

Secondary Outcome Measures

Median PFS
PFS will be computed from the date of start of treatment to the first documented date of progression or the date of death, due to any cause assessed by investigator.
PFS assessed at 12 weeks
Number of total patients who are PFS at 12 weeks of treatment
Overall survival (OS)
will be computed from the date of start of treatment to the date of death, due to any cause. Patients alive or lost for follow-up at the time of the analysis will be censored at the date of last follow-up

Full Information

First Posted
November 29, 2016
Last Updated
October 24, 2017
Sponsor
Assaf-Harofeh Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03096912
Brief Title
A Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well/Dedifferentiated Liposarcoma
Official Title
A Phase II Single Arm Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well-Differentiated or Dedifferentiated Liposarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Unknown status
Study Start Date
July 2016 (undefined)
Primary Completion Date
December 2019 (Anticipated)
Study Completion Date
April 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Assaf-Harofeh Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine whether ribociclib are effective and safe in the treatment of progressive well/dedifferentiated liposarcoma (WDL/DDL).
Detailed Description
The expected duration of this study is 36 months (24 months accrual period and 12 month follow up period). Enrollment into the screening or treatment phase of the study will be stopped when the actual subject numbers have been achieved. This single arm single institution, open label, prospective, phase II trial will evaluate the efficacy and safety of oral 600mg/daily in 28 day cycles of ribociclib in advanced well-differentiated liposarcoma (WDL) and de-differentiated liposarcoma (DDL) patients. Number of patients in the study will reflect the reconciliation between statistical requirements and incidence. Treatment will continue until disease progression, development of unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision. All screening requirements must be completed within 28 days of the visit (except for CDK4/6 amplification and pRb, p16 and cyclin D staining status which may be completed in advance). Patients will be examined on cycle 1 day-1 and every 2 weeks, including complete blood count (CBC) and chemistry, for the first 8 weeks of treatment, and thereafter every month until disease progression. CT/MRI imaging (contrast) will be performed every 8 weeks for response evaluation. Clinical benefit as well as individual categories of response (complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) will be determined using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST). Response duration endpoints, including PFS, PFS at 12 weeks and OS will be assessed using the Kaplan-Meier method. Toxicity (AEs) will be recorded using the NCI- Common Toxicity Criteria for Adverse Effects v 4.03 (NCI-CTCAE). Screening procedures will include medical history, physical examination, blood test, baseline CT/MRI imaging and formalin-fixed tissue submission for FoundationOne mutational analysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liposarcomas, Dedifferentiated, Liposarcoma - Well Differentiated, Liposarcoma; Mixed Type, Soft-Tissue Sarcoma
Keywords
CDK4 inhibitor, LEE011, ribociclib, liposarcoma dedifferentiated, liposarcoma well differentiated

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ribociclib
Arm Type
Experimental
Arm Description
Oral, ribociclib 600 mg x 1 a day, 21 days on 7 days off
Intervention Type
Drug
Intervention Name(s)
Ribociclib
Other Intervention Name(s)
LEE011
Intervention Description
Ribociclib Oral 600 mg x 1 a day 21 days on 1 week off in 28 days cycles
Primary Outcome Measure Information:
Title
Response to therapy as evaluated by RECIST 1.1
Time Frame
36 months
Title
Response to therapy as evaluated by Choi
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Median PFS
Description
PFS will be computed from the date of start of treatment to the first documented date of progression or the date of death, due to any cause assessed by investigator.
Time Frame
36 months
Title
PFS assessed at 12 weeks
Description
Number of total patients who are PFS at 12 weeks of treatment
Time Frame
12 weeks
Title
Overall survival (OS)
Description
will be computed from the date of start of treatment to the date of death, due to any cause. Patients alive or lost for follow-up at the time of the analysis will be censored at the date of last follow-up
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent Age ≥ 18 years Histological confirmed diagnosis of WDL/DDL with metastatic or locally advanced disease not amenable to complete resection WDL/DDL patients must have documentation of disease progression within 6 months prior to study entry Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Measurable disease by RECIST v1.1 criteria. At least one measurable lesion located outside of a previously irradiated area Formalin fixed paraffin embedded tumor blocs and representative hematoxylin/eosin slides (preferably both) should be provided for immunohistochemistry staining and molecular analysis of 50 gene signature panel and must have increased CDK4 gene copy number (at least >/=3) and proficient Rb gene Patient has adequate bone marrow and organ function Must be able to swallow ribociclib capsules/tablets Exclusion Criteria: A known hypersensitivity to ribociclib or any of its excipients A concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer Patients with central nervous system (CNS) involvement at least 4 weeks from prior therapy completion Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening) On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF >450 msec Participation in a prior investigational study within 30 days prior to enrollment Patient has had major surgery within 14 days prior to starting study drug
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daniela Katz, M.D
Phone
97289778144
Email
katzd@asaf.health.gov.il
First Name & Middle Initial & Last Name or Official Title & Degree
Sharona Ben Ami
Phone
97289778003
Email
sharonab@asaf.health.gov.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniela Katz, M.D
Organizational Affiliation
Assaf-Harofeh Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Assaf Harofeh Medical Center
City
Be'er Ya'aqov
ZIP/Postal Code
70300
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniela Katz, MD
Phone
97289778144
Email
katzd@asaf.health.gov.il
First Name & Middle Initial & Last Name & Degree
Sharona Ben Ami
Phone
97289778003
Email
sharonab@asaf.health.gov.il

12. IPD Sharing Statement

Plan to Share IPD
No

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A Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well/Dedifferentiated Liposarcoma

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