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

Liposarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02343172
• Other study ID #: CHDM201X2103C
• Status: Completed
• Phase: Phase 1
• Start date: March 13, 2015
• Est. completion date: October 16, 2019

Study information

• Verified date: June 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: October 16, 2019
• Est. primary completion date: October 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Liposarcoma

Intervention

Drug:
• HDM201

• LEE011

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Toronto	Ontario
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Lyon Cedex
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Ulm
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Taiwan	Novartis Investigative Site	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Canada,  France,  Germany,  Singapore,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment.	DLTs in the first cycle of treatment.	5 years
Primary	Phase Ib: Exposure to HDM201 and LEE011 as measured by AUC 0-24h	as measured by AUC0-24h	5 years
Primary	Phase II: Progression free survival (PFS)	To assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma	5 years
Secondary	Phase Ib/II: Incidence and severity of AEs and SAEs	Run-in part to assess safety of HDM201 in combination with LEE011	5 years
Secondary	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
Secondary	Phase Ib/II: dose intensity	Run-in part To assess tolerability of HDM201 in combination with LEE011	5 years
Secondary	Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Cmax	Run-in part to evaluate PK parameters of HDM201 and LEE011	5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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