Liposarcoma MedDRA version: 17.1 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 100000004864
Conditions
Interventions
Product Name: HDM201
Product Code: HDM201
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: no disponible
CAS Number: HDM201
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Male or Female age 18 years or older. ? Patients with histologically documented, locally advanced or metastatic WD/DD liposarcoma that has progressed on/or despite one prior systemic therapy. ? Patients with radiographic progression, defined by RECIST v.1.1, occurring while on/or within 6 months after last systemic treatment, prior to enrollment. ? Patients must have disease that can be evaluated by RECIST v1.1; measurable disease is required for patients enrolled in the Phase II. ? ECOG performance status of 0-1. ? Patients suitable and willing to undergo baseline biopsy. Other protocol-defined inclusion criteria may apply Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 29
Exclusion criteria
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. ? Impaired cardiac function. ? Inadequate organ function. ? Concomitant treatment with: Restriction in the use of moderate to strong inhibitors or inducers of CYP3A4/5, substrates of CYP3A4/5 with a narrow therapeutic index or medications with a known risk of prolonging the QT interval or inducing Torsades de Pointes. ? Concomitant treatment with colony-stimulating growth factors targeting the myeloid lineage (e.g. G-CSF, GM-CSF, M-CSF). Other protocol-defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase Ib: To determine the MTD and/or RP2D of HDM201 in combination with LEE011 in patients with liposarcoma. Phase2: To assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in patients with liposarcoma. ; Secondary Objective: Phase1b/2: 1. To characterize the safety and tolerability of HDM201 in combination with LEE011 2. To characterize the pharmacokinetic (PK) properties of HDM201 in combination with LEE011 and potential metabolite/s when feasible 3. To assess the pharmacodynamic (PD) effect of HDM201 in combination with LEE011 and a potential relationship with clinical outcome Phase Ib: To assess preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma Phase II To further assess the anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma ; Primary end point(s): Phase1b: 1. Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment 2. Exposure to HDM201 and LEE011 as measured by AUC0-24h at C1D14 Phase 2: PFS as per RECIST 1.1, assessed by investigator ; Timepoint(s) of evaluation of this end point: Phase1b: 1. First cycle of treatment (28 days for Regimen 1 and 3 / 35 days for Regimen 2) 2. For all regimens: on D1, 2, 8, 14, 15 for Cycle1 Phase 2: PFS at 12 and 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1b/2: 1. Safety: Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, ECG Tolerability: Dose interruptions, reductions and dose intensity. 2. Time vs. plasma concentration profiles, PK parameters of HDM201 and LEE011 and potential metabolite/s when feasible 3. Anti-tumor activity endpoint (BOR, PFS) and changes from baseline of PD markers: - In tumor tissue (e.g. p21, PUMA, MDM2) - In blood (e.g. GDF-15) Phase1b: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator Phase 2: - BOR, ORR and DOR as per RECIST v 1.1 assessed by investigator - OS ; Timepoint(s) of evaluation of this end point: Phase 1b/2: 1. Every cycle 2. For all regimens: on D1, 2, 8, 14, 15 for Cycle1 - on D1, 8, 14 for Cycle 2 and on D14 for Cycle 3 and 4 3. Baseline, up to 14 days Phase1b: BOR, ORR and PFS at 6 months Phase 2: - BOR, ORR and DOR at 6 months - OS at 12 months | — |
Countries
Canada, France, Germany, Singapore, Spain, Taiwan, United States
Contacts
Public ContactDepartamento Médico Oncología (GMO)
Novartis Farmacéutica, S.A.
Outcome results
None listed