LiposarcomaPhase 2NCT02571829
A Phase II Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well/Dedifferentiated Liposarcoma
A Phase 2 study testing ribociclib in people with Liposarcoma and Soft Tissue Sarcoma, run by Hadassah Medical Organization at 1 site in Israel.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liposarcoma, Soft Tissue Sarcoma
- What is being tested?
- ribociclib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteIsrael
- Study dates
- May 2016to Oct 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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).
Read the 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 quantitative analysis of CDK4 gene copy number using FISH, immunostaining for p16 and cyclin D1 all using formalin fixed paraffin embedded (FFPE) tissue sections. In addition tumor DNA, extracted from FFPE tissue (after choosing optimal area by a Pathologist), will be submitted to a next generation sequencing analysis ("ion ampliseq" cancer panel v2©) for a later exploratory analysis.
- Conditions
- Liposarcoma, Soft Tissue Sarcoma
- Being tested
- ribociclib
- Keywords
- Liposarcoma, Soft tissue sarcoma, CDK4, CDK6, LEE011, ribociclib
- Medical subject headings
- Liposarcoma, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ribociclibDrug
Also called LEE011
Oral, 600 mg x 1 a day, duration - according to response
| Study group | Role | What they receive |
|---|---|---|
| ribociclib | Experimental | single arm ribociclib Oral 600 mg x 1 a day duration according to response. Receives: Drug: ribociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to therapy as evaluated by RECIST 1.1 and Choi
Measured: 36 months (24 months accrual period and 12 month follow up period)
Secondary outcomes (3)
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.
Measured: 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.
Measured: 36 months (24 months accrual period and 12 month follow up period)
Evaluate the time from first documented response to disease progression
Measured: 36 months (24 months accrual period and 12 month follow up period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2015 (estimated)
- Study startMay 2016
- Primary completionAug 2017 (estimated)
- Study completionOct 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for LiposarcomaStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniela Katz, Hadassah Medical Organization
- Investigators
- Daniela Katz, MD, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02571829
- Sponsor's protocol ID
- CLEE011-HMO-CTIL
- Status last verified
- Nov 2016
- First submitted
- 6 Oct 2015
- Last updated
- 23 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Shapiro 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.
PubMed 16603719Ortega 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.
PubMed 11960696Barretina 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.
PubMed 20601955Dickson 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.
PubMed 23569312Van 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.
PubMed 11872347
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Single Arm Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well-Differentiated or Dedifferentiated Liposarcoma
- ClinicalTrials.gov ID
- NCT02571829
- Acronym / sponsor ID
- CLEE011-HMO-CTIL
- Conditions
- Liposarcoma, Soft Tissue Sarcoma
- Keywords
- Liposarcoma, Soft tissue sarcoma, CDK4, CDK6, LEE011, ribociclib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- May 2016
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Oct 2017 (estimated)
- First posted
- 8 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 quantitative analysis of CDK4 gene copy number using FISH, immunostaining for p16 and cyclin D1 all using formalin fixed paraffin embedded (FFPE) tissue sections. In addition tumor DNA, extracted from FFPE tissue (after choosing optimal area by a Pathologist), will be submitted to a next generation sequencing analysis ("ion ampliseq" cancer panel v2©) for a later exploratory analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ribociclib | Experimental | Drug: ribociclibsingle arm ribociclib Oral 600 mg x 1 a day duration according to response. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ribociclibAlso: LEE011Oral, 600 mg x 1 a day, duration - according to response | Drug | ribociclib |
Primary outcome
Response to therapy as evaluated by RECIST 1.1 and Choi
Time frame: 36 months (24 months accrual period and 12 month follow up period)
3 secondary outcomes
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.
Time frame: 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.
Time frame: 36 months (24 months accrual period and 12 month follow up period)
Evaluate the time from first documented response to disease progression
Time frame: 36 months (24 months accrual period and 12 month follow up period)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2016.
- Background: PubMed 16603719Shapiro 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.
- Background: PubMed 11960696Ortega 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.
- Background: PubMed 20601955Barretina 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.
- Background: PubMed 23569312Dickson 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.
- Background: PubMed 11872347Van 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniela Katz, MD principal investigator
Hadassah Medical Organization
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ribociclib in people with Liposarcoma and Soft Tissue Sarcoma, run by Hadassah Medical Organization at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response to therapy as evaluated by RECIST 1.1 and Choi (time frame: 36 months (24 months accrual period and 12 month follow up period)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02571829, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2016.