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

A Phase II Single Arm Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well-Differentiated or Dedifferentiated Liposarcoma

The purpose of this study is to determine whether ribociclib are effective and safe in the treatment of progressive well/dedifferentiated liposarcoma (WDL/DDL).

Study Overview

• Status: Unknown
• Conditions: Soft-Tissue Sarcoma; Liposarcomas, Dedifferentiated; Liposarcoma - Well Differentiated; Liposarcoma; Mixed Type
• Intervention / Treatment: Drug: Ribociclib

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
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sharona Ben Ami; Phone Number: 97289778003; Email: sharonab@asaf.health.gov.il
• Study Contact Backup: Name: Daniela Katz, M.D; Phone Number: 97289778144; Email: katzd@asaf.health.gov.il

Study Locations

• Israel
  • Be'er Ya'aqov, Israel, 70300
    • Recruiting
    • Assaf Harofeh Medical Center
    • Contact: Daniela Katz, MD; Phone Number: 97289778144; Email: katzd@asaf.health.gov.il
    • Contact: Sharona Ben Ami; Phone Number: 97289778003; Email: sharonab@asaf.health.gov.il

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: LEE011

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response to therapy as evaluated by RECIST 1.1	36 months
Response to therapy as evaluated by Choi	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	36 months
PFS assessed at 12 weeks	Number of total patients who are PFS at 12 weeks of treatment	12 weeks
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	36 months

Collaborators and Investigators

• Sponsor: Assaf-Harofeh Medical Center
• Investigators: Principal Investigator: Daniela Katz, M.D, Assaf-Harofeh Medical Center

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (ANTICIPATED): December 1, 2019
• Study Completion (ANTICIPATED): April 1, 2020

Study Registration Dates

• First Submitted: November 29, 2016
• First Submitted That Met QC Criteria: March 26, 2017
• First Posted (ACTUAL): March 30, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 25, 2017
• Last Update Submitted That Met QC Criteria: October 24, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: LEE011; ribociclib; CDK4 inhibitor; liposarcoma dedifferentiated; liposarcoma well differentiated
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Adipose Tissue; Sarcoma; Liposarcoma
• Other Study ID Numbers: 243/16

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No