An interventional study of oral HDM201 in combination with oral LEE011 in adult patients with liposarcoma

• Register: EUCTR
• Last refreshed on: 19 October 2020
• Main ID: EUCTR2014-003604-75-DE
• Date of registration: 13/05/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services 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: 09/06/2015
• Target sample size: 84
• 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: 2
• 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

Contacts

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

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 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.
• 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 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42

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. And depending on regimen, restriction in the use of:
substrates of CYP2C19 with a narrow therapeutic index or substrates of OATP1B1, P-gp substrates.
• 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: 20.0 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Code: HDM201 2,5mg
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 10 mg
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 100 mg
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 1mg
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 50 mg
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 200 mg
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: 200-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Phase1b:
1. First cycle of treatment (21 days for Regimen 4, 28 days for Regimen 1, Regimen 3 and Regimen 5, or 35 days for Regimen 2)
2. For all regimens: on D1, 2, 14, 15 cycle1 and on D1, 2 cycle 2

Phase 2:
PFS at 12 and 24 weeks

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

Phase 2:
PFS as per RECIST 1.1, assessed by investigator

Main Objective: Phase Ib: To determine the MTD and/or RP2D of HDM201 in combination with LEE011 in patients with liposarcoma using two different HDM201 dosing schedules.

Phase2: To assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in patients with 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. Regimen 1, 2,and 3: on D1, 2, 8, 14, 15 for Cycle1/ D1, 8 and 14 on cycle 2 and on D14 for C3 /C4 only
Regimen 4 and 5 (HDM201): on D1, 2, 3 for cycle 1 /on D1, 2 for cycle 2.
Regimen 4 and 5 (LEE011): on D1, 2, 3, 8, 14, 15 Cycle 1 /D1, 2, 8, 14 for cycle 2 and on D14 for C3/C4 only
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

Ethics review

Status: Approved
Approval date: 09/06/2015
Contact:

Results

• Results available: Yes
• Date Posted: 02/10/2020
• Date Completed: 16/10/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-003604-75/results