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

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ClinicalTrials.gov Identifier: NCT03096912
Recruitment Status : Recruiting
First Posted : March 30, 2017
Last Update Posted : October 25, 2017
Sponsor:
Information provided by (Responsible Party):
Daniela Katz M.D, Assaf-Harofeh Medical Center

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).

Condition or disease Intervention/treatment Phase
Liposarcomas, Dedifferentiated Liposarcoma - Well Differentiated Liposarcoma; Mixed Type Soft-Tissue Sarcoma Drug: Ribociclib Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Single Arm Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well-Differentiated or Dedifferentiated Liposarcoma
Study Start Date : July 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Ribociclib

Arm Intervention/treatment
Experimental: Ribociclib
Oral, ribociclib 600 mg x 1 a day, 21 days on 7 days off
Drug: Ribociclib
Ribociclib Oral 600 mg x 1 a day 21 days on 1 week off in 28 days cycles
Other Name: LEE011




Primary Outcome Measures :
  1. Response to therapy as evaluated by RECIST 1.1 [ Time Frame: 36 months ]
  2. Response to therapy as evaluated by Choi [ Time Frame: 36 months ]

Secondary Outcome Measures :
  1. Median PFS [ Time Frame: 36 months ]
    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.

  2. PFS assessed at 12 weeks [ Time Frame: 12 weeks ]
    Number of total patients who are PFS at 12 weeks of treatment

  3. Overall survival (OS) [ Time Frame: 36 months ]
    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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03096912


Contacts
Contact: Daniela Katz, M.D 97289778144 katzd@asaf.health.gov.il
Contact: Sharona Ben Ami 97289778003 sharonab@asaf.health.gov.il

Locations
Israel
Assaf Harofeh Medical Center Recruiting
Be'er Ya'aqov, Israel, 70300
Contact: Daniela Katz, MD    97289778144    katzd@asaf.health.gov.il   
Contact: Sharona Ben Ami    97289778003    sharonab@asaf.health.gov.il   
Sponsors and Collaborators
Assaf-Harofeh Medical Center
Investigators
Principal Investigator: Daniela Katz, M.D Assaf-Harofeh Medical Center

Responsible Party: Daniela Katz M.D, M.D, Assaf-Harofeh Medical Center
ClinicalTrials.gov Identifier: NCT03096912     History of Changes
Other Study ID Numbers: 243/16
First Posted: March 30, 2017    Key Record Dates
Last Update Posted: October 25, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Daniela Katz M.D, Assaf-Harofeh Medical Center:
CDK4 inhibitor
LEE011
ribociclib
liposarcoma dedifferentiated
liposarcoma well differentiated

Additional relevant MeSH terms:
Sarcoma
Liposarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Adipose Tissue