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

A Phase Ib/II, Open-label, Multicenter Study of Oral HDM201 in Combination With Oral LEE011 in Adult Patients With Liposarcoma

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.

Study Overview

• Status: Completed
• Conditions: Liposarcoma
• Intervention / Treatment: Drug: LEE011; Drug: HDM201

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
• France
  • Bordeaux, France, 33076
    • Novartis Investigative Site
  • Lyon Cedex, France, 69373
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28222
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site

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:

• 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.

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: HDM201+LEE011	Drug: LEE011; Drug: HDM201

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment.	DLTs in the first cycle of treatment.	5 years
Phase Ib: Exposure to HDM201 and LEE011 as measured by AUC 0-24h	as measured by AUC0-24h	5 years
Phase II: Progression free survival (PFS)	To assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib/II: Incidence and severity of AEs and SAEs	Run-in part to assess safety of HDM201 in combination with LEE011	5 years
Phase Ib/II: number of patients with dose interruptions and reduction	Run-in part To assess tolerability of HDM201 in combination with LEE011	5 years
Phase Ib/II: dose intensity	Run-in part To assess tolerability of HDM201 in combination with LEE011	5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Cmax	Run-in part to evaluate PK parameters of HDM201 and LEE011	5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Tmax	Run-in part to evaluate the PK parameters of HDM201 and LEE011	5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUClast	Run-in part to evaluate the PK parameters of HDM201 and LEE011	5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUCtau	Run-in part to evaluate the PK parameters of HDM201 and LEE011	5 years
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.	5 years
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.	5 years
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	5 years
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	5 years
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	5 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CHDM201X2103C can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 13, 2015
• Primary Completion (ACTUAL): October 16, 2019
• Study Completion (ACTUAL): October 16, 2019

Study Registration Dates

• First Submitted: January 5, 2015
• First Submitted That Met QC Criteria: January 15, 2015
• First Posted (ESTIMATE): January 21, 2015

Study Record Updates

• Last Update Posted (ACTUAL): December 9, 2020
• Last Update Submitted That Met QC Criteria: December 6, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: LEE011; HDM201; Liposarcoma; MDM2 inhibition; cdk4 inhibition
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Adipose Tissue; Liposarcoma
• Other Study ID Numbers: CHDM201X2103C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No