Clinical trial · Interventional

A Phase II 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

NCT02571829CI-TRIAL-00024886unknownPhase 2ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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

Conditions

Conditions (2)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Liposarcoma	Liposarcoma	ONTOLOGY_EXACT	0.90
Soft Tissue Sarcoma	Soft Tissue Sarcoma	ONTOLOGY_EXACT	0.90

Interventions

Interventions (1)

Intervention	Type	Mapped drug	Match
ribociclib	Drug	Ribociclib	ALIAS

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
ribociclib
description
single arm ribociclib Oral 600 mg x 1 a day duration according to response.
interventionNames
1. Drug: ribociclib

Primary outcomes (1)

measure
Response to therapy as evaluated by RECIST 1.1 and Choi
timeFrame
36 months (24 months accrual period and 12 month follow up period)

Secondary outcomes (3)

measure
Median PFS and PFS assessed at 12 weeks (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.
timeFrame
12 weeks

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

Inclusion Criteria:

1. Written informed consent
2. Age ≥ 18 years
3. Histological confirmed diagnosis of WDL/DDL with metastatic or locally advanced disease not amenable to complete resection.
4. WDL/DDL patients must have documentation of disease progression within 6 months prior to study entry.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Measurable disease by RECIST v1.1 criteria. At least one measurable lesion located outside of a previously irradiated area.
7. 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.
8. Patient has adequate bone marrow and organ function.
9. Must be able to swallow ribociclib capsules/tablets.

Exclusion Criteria:

1. A known hypersensitivity to ribociclib or any of its excipients.
2. 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.
3. Patients with central nervous system (CNS) involvement at least 4 weeks from prior therapy completion
4. 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)
5. On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF \>450 msec
6. Participation in a prior investigational study within 30 days prior to enrollment
7. Patient has had major surgery within 14 days prior to starting study drug

References

Publications (5)

BACKGROUNDShapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 2006 Apr 10;24(11):1770-83. doi: 10.1200/JCO.2005.03.7689. PMID 16603719
BACKGROUNDOrtega S, Malumbres M, Barbacid M. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophys Acta. 2002 Mar 14;1602(1):73-87. doi: 10.1016/s0304-419x(02)00037-9. PMID 11960696
BACKGROUNDBarretina J, Taylor BS, Banerji S, Ramos AH, Lagos-Quintana M, Decarolis PL, Shah K, Socci ND, Weir BA, Ho A, Chiang DY, Reva B, Mermel CH, Getz G, Antipin Y, Beroukhim R, Major JE, Hatton C, Nicoletti R, Hanna M, Sharpe T, Fennell TJ, Cibulskis K, Onofrio RC, Saito T, Shukla N, Lau C, Nelander S, Silver SJ, Sougnez C, Viale A, Winckler W, Maki RG, Garraway LA, Lash A, Greulich H, Root DE, Sellers WR, Schwartz GK, Antonescu CR, Lander ES, Varmus HE, Ladanyi M, Sander C, Meyerson M, Singer S. Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet. 2010 Aug;42(8):715-21. doi: 10.1038/ng.619. Epub 2010 Jul 4. PMID 20601955
BACKGROUNDDickson MA, Tap WD, Keohan ML, D'Angelo SP, Gounder MM, Antonescu CR, Landa J, Qin LX, Rathbone DD, Condy MM, Ustoyev Y, Crago AM, Singer S, Schwartz GK. Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma. J Clin Oncol. 2013 Jun 1;31(16):2024-8. doi: 10.1200/JCO.2012.46.5476. Epub 2013 Apr 8. PMID 23569312
BACKGROUNDVan Glabbeke M, Verweij J, Judson I, Nielsen OS; EORTC Soft Tissue and Bone Sarcoma Group. Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas. Eur J Cancer. 2002 Mar;38(4):543-9. doi: 10.1016/s0959-8049(01)00398-7. PMID 11872347

Registry

Dates and enrollment

Start: May 1, 2016
Primary completion: Aug 1, 2017
Completion: Oct 1, 2017
First posted: Oct 8, 2015
Last update posted: Nov 23, 2016
Enrollment: 30 (estimated)
Lead sponsor: Hadassah Medical Organization OTHER
Keywords: Liposarcoma, Soft tissue sarcoma, CDK4, CDK6, LEE011, ribociclib

Data updated 22 days agoSource updated Nov 23, 2016source: clinicaltrials

Locations

Locations by country (1)

Country	Sites	Recruiting
Israel	1	0

Trial listing is informational. Eligibility is decided by the study team; contact information is on ClinicalTrials.gov.