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Study of Safety and Efficacy of HDM201 in Combination With LEE011 in Patients With Liposarcoma

Primary Purpose

Liposarcoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
HDM201
LEE011
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liposarcoma focused on measuring Liposarcoma, MDM2 inhibition, cdk4 inhibition, HDM201, LEE011

Eligibility Criteria

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

Inclusion Criteria:

  • Patients with histologically documented, locally advanced or metastatic WD/DD liposarcoma who have received at least one prior systemic therapy
  • Patients with radiologic progression, defined by RECIST v.1.1, occurring while on/or within 6 months after last systemic treatment, prior to enrollment
  • ECOG performance status of 0-1

Exclusion Criteria:

  • Prior treatment with compounds with the same mode of action
  • Patients with TP53 mutated tumors, if the molecular status is known
  • Symptomatic central nervous system metastases
  • Inadequate organ function
  • Previous and concomitant therapy that precludes enrollment, as defined by protocol

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HDM201+LEE011

Arm Description

Outcomes

Primary Outcome Measures

Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment.
DLTs in the first cycle of treatment.
Phase Ib: Exposure to HDM201 and LEE011 as measured by AUC 0-24h
as measured by AUC0-24h
Phase II: Progression free survival (PFS)
To assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma

Secondary Outcome Measures

Phase Ib/II: Incidence and severity of AEs and SAEs
Run-in part to assess safety of HDM201 in combination with LEE011
Phase Ib/II: number of patients with dose interruptions and reduction
Run-in part To assess tolerability of HDM201 in combination with LEE011
Phase Ib/II: dose intensity
Run-in part To assess tolerability of HDM201 in combination with LEE011
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Cmax
Run-in part to evaluate PK parameters of HDM201 and LEE011
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Tmax
Run-in part to evaluate the PK parameters of HDM201 and LEE011
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUClast
Run-in part to evaluate the PK parameters of HDM201 and LEE011
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUCtau
Run-in part to evaluate the PK parameters of HDM201 and LEE011
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in blood (GDF-15)
Run-in part measure of GDF-15 fold-change in protein levels (PD direct targets of p53) to assess PD changes from baseline in blood and a potential relationship with clinical outcome.
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in tumor tissue (p21, MDM2)
Run-in part measure of p21 and MDM2 protein levels by IHC (H-Score) (p53 and CDK4 pathways) to assess changes from baseline of PD markers in tumor tissue and a potential relationship with clinical outcome.
Phase Ib/II: anti-tumor activity endpoint (BOR, PFS)
Run-in part to assess PD effect of HDM201 and LEE011 and a potential relationship with clinical outcome
Phase Ib: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
Run-in part to assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Phase II: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
Run-in part to further assess the anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma

Full Information

First Posted
January 5, 2015
Last Updated
December 6, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02343172
Brief Title
Study of Safety and Efficacy of HDM201 in Combination With LEE011 in Patients With Liposarcoma
Official Title
A Phase Ib/II, Open-label, Multicenter Study of Oral HDM201 in Combination With Oral LEE011 in Adult Patients With Liposarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
March 13, 2015 (Actual)
Primary Completion Date
October 16, 2019 (Actual)
Study Completion Date
October 16, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To determine the MTD/RP2D of the HDM201 and LEE011 combination and evaluate whether the combination is safe and has beneficial effects in patients with liposarcoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liposarcoma
Keywords
Liposarcoma, MDM2 inhibition, cdk4 inhibition, HDM201, LEE011

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HDM201+LEE011
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
HDM201
Intervention Type
Drug
Intervention Name(s)
LEE011
Primary Outcome Measure Information:
Title
Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment.
Description
DLTs in the first cycle of treatment.
Time Frame
5 years
Title
Phase Ib: Exposure to HDM201 and LEE011 as measured by AUC 0-24h
Description
as measured by AUC0-24h
Time Frame
5 years
Title
Phase II: Progression free survival (PFS)
Description
To assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Phase Ib/II: Incidence and severity of AEs and SAEs
Description
Run-in part to assess safety of HDM201 in combination with LEE011
Time Frame
5 years
Title
Phase Ib/II: number of patients with dose interruptions and reduction
Description
Run-in part To assess tolerability of HDM201 in combination with LEE011
Time Frame
5 years
Title
Phase Ib/II: dose intensity
Description
Run-in part To assess tolerability of HDM201 in combination with LEE011
Time Frame
5 years
Title
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Cmax
Description
Run-in part to evaluate PK parameters of HDM201 and LEE011
Time Frame
5 years
Title
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Tmax
Description
Run-in part to evaluate the PK parameters of HDM201 and LEE011
Time Frame
5 years
Title
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUClast
Description
Run-in part to evaluate the PK parameters of HDM201 and LEE011
Time Frame
5 years
Title
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUCtau
Description
Run-in part to evaluate the PK parameters of HDM201 and LEE011
Time Frame
5 years
Title
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in blood (GDF-15)
Description
Run-in part measure of GDF-15 fold-change in protein levels (PD direct targets of p53) to assess PD changes from baseline in blood and a potential relationship with clinical outcome.
Time Frame
5 years
Title
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in tumor tissue (p21, MDM2)
Description
Run-in part measure of p21 and MDM2 protein levels by IHC (H-Score) (p53 and CDK4 pathways) to assess changes from baseline of PD markers in tumor tissue and a potential relationship with clinical outcome.
Time Frame
5 years
Title
Phase Ib/II: anti-tumor activity endpoint (BOR, PFS)
Description
Run-in part to assess PD effect of HDM201 and LEE011 and a potential relationship with clinical outcome
Time Frame
5 years
Title
Phase Ib: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
Description
Run-in part to assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Time Frame
5 years
Title
Phase II: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
Description
Run-in part to further assess the anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with histologically documented, locally advanced or metastatic WD/DD liposarcoma who have received at least one prior systemic therapy Patients with radiologic progression, defined by RECIST v.1.1, occurring while on/or within 6 months after last systemic treatment, prior to enrollment ECOG performance status of 0-1 Exclusion Criteria: Prior treatment with compounds with the same mode of action Patients with TP53 mutated tumors, if the molecular status is known Symptomatic central nervous system metastases Inadequate organ function Previous and concomitant therapy that precludes enrollment, as defined by protocol Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Novartis Investigative Site
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Novartis Investigative Site
City
Lyon Cedex
ZIP/Postal Code
69373
Country
France
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17708
Description
Results for CHDM201X2103C can be found on the Novartis Clinical Trial Results Website

Learn more about this trial

Study of Safety and Efficacy of HDM201 in Combination With LEE011 in Patients With Liposarcoma

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