Clinical trial NCT02343172: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Liposarcoma
Keywords: Liposarcoma
MDM2 inhibition
cdk4 inhibition
HDM201
LEE011
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-01-21
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment.
timeFrame: 5 years
measure: Phase Ib: Exposure to HDM201 and LEE011 as measured by AUC 0-24h
timeFrame: 5 years
measure: Phase II: Progression free survival (PFS)
timeFrame: 5 years
Secondary outcomes:
measure: Phase Ib/II: Incidence and severity of AEs and SAEs
timeFrame: 5 years
measure: Phase Ib/II: number of patients with dose interruptions and reduction
timeFrame: 5 years
measure: Phase Ib/II: dose intensity
timeFrame: 5 years
measure: Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Cmax
timeFrame: 5 years
measure: Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Tmax
timeFrame: 5 years
measure: Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUClast
timeFrame: 5 years
measure: Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUCtau
timeFrame: 5 years
measure: Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in blood (GDF-15)
timeFrame: 5 years
measure: Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in tumor tissue (p21, MDM2)
timeFrame: 5 years
measure: Phase Ib/II: anti-tumor activity endpoint (BOR, PFS)
timeFrame: 5 years
measure: Phase Ib: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
timeFrame: 5 years
measure: Phase II: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
timeFrame: 5 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: