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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 10 December 2019
Main ID:  EUCTR2014-003604-75-FR
Date of registration: 14/08/2015
Prospective Registration: No
Primary sponsor: Novartis Pharma AG
Public title: An interventional study of oral HDM201 in combination with oral LEE011 in adult patients with liposarcoma
Scientific title: A Phase Ib/II, open-label, multicenter study of oral HDM201 in combination with oral LEE011 in adult patients with liposarcoma
Date of first enrolment: 16/02/2015
Target sample size: 59
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003604-75
Study type:  Interventional clinical trial of medicinal product
Study design: 
Controlled: no
Randomised: no
Open: yes
Single blind: no
Double blind: no
Parallel group: no
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: no
Number of treatment arms in the trial: 1
 
Phase:  Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
Canada France Germany Singapore Spain Taiwan United States
Contacts
Name: Information Communication Médicale   
Address:  2-4 rue Lionel Terray 92500 Rueil-Malmaison France
Telephone: +3315547 6600
Email: icm.phfr@novartis.com
Affiliation:  Novartis Phrama S.A.S.
Name: Information Communication Médicale   
Address:  2-4 rue Lionel Terray 92500 Rueil-Malmaison France
Telephone: +3315547 6600
Email: icm.phfr@novartis.com
Affiliation:  Novartis Phrama S.A.S.
Key inclusion & exclusion 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:
• 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Liposarcoma
MedDRA version: 18.0 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]
Intervention(s)

Product Code: HDM201
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not yet available
Current Sponsor code: HDM201
Other descriptive name: HDM201
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Product Code: HDM201
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not yet available
Current Sponsor code: HDM201
Other descriptive name: HDM201
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Code: HDM201
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not yet available
Current Sponsor code: HDM201
Other descriptive name: HDM201
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Code: HDM201
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not yet available
Current Sponsor code: HDM201
Other descriptive name: HDM201
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Product Code: LEE011
Pharmaceutical Form: Capsule
INN or Proposed INN: not yet available
Current Sponsor code: LEE011
Other descriptive name: LEE011
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Code: LEE011
Pharmaceutical Form: Capsule
INN or Proposed INN: not yet available
Primary Outcome(s)

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

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.

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

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
Secondary Outcome(s)

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
Secondary ID(s)
CHDM201X2103C
2014-003604-75-ES
Source(s) of Monetary Support
Novartis Pharma Services AG
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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