Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
CHDM201X2103C
- NCT ID:
NCT02343172
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| HDM201 | | HDM201+LEE011 |
| LEE011 | | HDM201+LEE011 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| HDM201+LEE011 | Experimental | | |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment. |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | DLTs in the first cycle of treatment. |
Secondary Outcome Measures
| Measure: | Phase Ib/II: Incidence and severity of AEs and SAEs |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Run-in part to assess safety of HDM201 in combination with LEE011 |
| Measure: | Phase Ib/II: number of patients with dose interruptions and reduction |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Run-in part To assess tolerability of HDM201 in combination with LEE011 |
| Measure: | Phase Ib/II: dose intensity |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Run-in part To assess tolerability of HDM201 in combination with LEE011 |
| Measure: | Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Cmax |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Run-in part to evaluate PK parameters of HDM201 and LEE011 |
| Measure: | Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Tmax |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Run-in part to evaluate the PK parameters of HDM201 and LEE011 |
| Measure: | Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUClast |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Run-in part to evaluate the PK parameters of HDM201 and LEE011 |
| Measure: | Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUCtau |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Run-in part to evaluate the PK parameters of HDM201 and LEE011 |
| Measure: | Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in blood (GDF-15) |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in tumor tissue (p21, MDM2) |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Phase Ib/II: anti-tumor activity endpoint (BOR, PFS) |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Run-in part to assess PD effect of HDM201 and LEE011 and a potential relationship with clinical outcome |
| Measure: | Phase Ib: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Run-in part to assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma |
| Measure: | Phase II: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Run-in part to further assess the anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Liposarcoma
- MDM2 inhibition
- cdk4 inhibition
- HDM201
- LEE011
Last Updated
December 9, 2020
