Study of Safety and Efficacy of HDM201 in Combination With LEE011 in Patients With Liposarcoma
- Registration Number
- NCT02343172
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 74
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description HDM201+LEE011 HDM201 - HDM201+LEE011 LEE011 -
- Primary Outcome Measures
Name Time Method Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment. 5 years DLTs in the first cycle of treatment.
Phase Ib: Exposure to HDM201 and LEE011 as measured by AUC 0-24h 5 years as measured by AUC0-24h
Phase II: Progression free survival (PFS) 5 years To assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
- Secondary Outcome Measures
Name Time Method Phase Ib/II: Incidence and severity of AEs and SAEs 5 years Run-in part to assess safety of HDM201 in combination with LEE011
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUCtau 5 years Run-in part to evaluate the PK parameters of HDM201 and LEE011
Phase Ib: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator 5 years Run-in part to assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Phase Ib/II: number of patients with dose interruptions and reduction 5 years Run-in part To assess tolerability of HDM201 in combination with LEE011
Phase II: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator 5 years Run-in part to further assess the anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Tmax 5 years Run-in part to evaluate the PK parameters of HDM201 and LEE011
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUClast 5 years Run-in part to evaluate the PK parameters of HDM201 and LEE011
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in tumor tissue (p21, MDM2) 5 years 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) 5 years Run-in part to assess PD effect of HDM201 and LEE011 and a potential relationship with clinical outcome
Phase Ib/II: dose intensity 5 years Run-in part To assess tolerability of HDM201 in combination with LEE011
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in blood (GDF-15) 5 years 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: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Cmax 5 years Run-in part to evaluate PK parameters of HDM201 and LEE011
Trial Locations
- Locations (1)
Novartis Investigative Site
🇨🇳Taipei, Taiwan