LiposarcomaPhase 1NCT02343172
Study of Safety and Efficacy of HDM201 in Combination With LEE011 in Patients With Liposarcoma
A Phase 1 study testing HDM201 and LEE011 in people with Liposarcoma, run by Novartis Pharmaceuticals at 9 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liposarcoma
- What is being tested?
- HDM201 and LEE011
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 9 sitesin 6 countries
- Study dates
- 13 Mar 2015to 16 Oct 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
9 sites in 6 countries.
9 sites in 6 countries
France2 sites
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Lyon, 69373
Germany2 sites
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Ulm, 89081
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28222
About this study
Official title: A Phase Ib/II, Open-label, Multicenter Study of Oral HDM201 in Combination With Oral LEE011 in Adult Patients With Liposarcoma
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.
- Conditions
- Liposarcoma
- Being tested
- HDM201, LEE011
- Keywords
- Liposarcoma, MDM2 inhibition, cdk4 inhibition, HDM201, LEE011
- Medical subject headings
- Liposarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HDM201Drug
LEE011Drug
| Study group | Role | What they receive |
|---|---|---|
| HDM201+LEE011 | Experimental | Not described Receives: Drug: HDM201; Drug: LEE011 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment.
DLTs in the first cycle of treatment.
Measured: 5 years
Phase Ib: Exposure to HDM201 and LEE011 as measured by AUC 0-24h
as measured by AUC0-24h
Measured: 5 years
Phase II: Progression free survival (PFS)
To assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Measured: 5 years
Secondary outcomes (12)
Phase Ib/II: Incidence and severity of AEs and SAEs
Run-in part to assess safety of HDM201 in combination with LEE011
Measured: 5 years
Phase Ib/II: number of patients with dose interruptions and reduction
Run-in part To assess tolerability of HDM201 in combination with LEE011
Measured: 5 years
Phase Ib/II: dose intensity
Run-in part To assess tolerability of HDM201 in combination with LEE011
Measured: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Cmax
Run-in part to evaluate PK parameters of HDM201 and LEE011
Measured: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Tmax
Run-in part to evaluate the PK parameters of HDM201 and LEE011
Measured: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUClast
Run-in part to evaluate the PK parameters of HDM201 and LEE011
Measured: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUCtau
Run-in part to evaluate the PK parameters of HDM201 and LEE011
Measured: 5 years
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in blood (GDF-15)
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.
Measured: 5 years
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in tumor tissue (p21, MDM2)
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.
Measured: 5 years
Phase Ib/II: anti-tumor activity endpoint (BOR, PFS)
Run-in part to assess PD effect of HDM201 and LEE011 and a potential relationship with clinical outcome
Measured: 5 years
Phase Ib: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
Run-in part to assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Measured: 5 years
Phase II: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
Run-in part to further assess the anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2015 (estimated)
- Study start13 Mar 2015
- Primary completion16 Oct 2019
- Study completion16 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LiposarcomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02343172
- Sponsor's protocol ID
- CHDM201X2103C
- Status last verified
- Jun 2020
- First submitted
- 5 Jan 2015
- Last updated
- 9 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II, Open-label, Multicenter Study of Oral HDM201 in Combination With Oral LEE011 in Adult Patients With Liposarcoma
- ClinicalTrials.gov ID
- NCT02343172
- Acronym / sponsor ID
- CHDM201X2103C
- Conditions
- Liposarcoma
- Keywords
- Liposarcoma, MDM2 inhibition, cdk4 inhibition, HDM201, LEE011
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 13 Mar 2015 (actual)
- Primary completion
- 16 Oct 2019 (actual)
- Study completion
- 16 Oct 2019 (actual)
- First posted
- 21 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HDM201+LEE011 | Experimental | Drug: HDM201, Drug: LEE011 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HDM201 | Drug | HDM201+LEE011 |
| LEE011 | Drug | HDM201+LEE011 |
Primary outcome
Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment.
Time frame: 5 years
DLTs in the first cycle of treatment.
Phase Ib: Exposure to HDM201 and LEE011 as measured by AUC 0-24h
Time frame: 5 years
as measured by AUC0-24h
Phase II: Progression free survival (PFS)
Time frame: 5 years
To assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
12 secondary outcomes
Phase Ib/II: Incidence and severity of AEs and SAEs
Time frame: 5 years
Phase Ib/II: number of patients with dose interruptions and reduction
Time frame: 5 years
Phase Ib/II: dose intensity
Time frame: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Cmax
Time frame: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Tmax
Time frame: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUClast
Time frame: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUCtau
Time frame: 5 years
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in blood (GDF-15)
Time frame: 5 years
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in tumor tissue (p21, MDM2)
Time frame: 5 years
Phase Ib/II: anti-tumor activity endpoint (BOR, PFS)
Time frame: 5 years
Phase Ib: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
Time frame: 5 years
Phase II: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2020.
- Results for CHDM201X2103C can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
9 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HDM201 and LEE011 in people with Liposarcoma, run by Novartis Pharmaceuticals at 9 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France, Germany, Spain, Canada, Singapore and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment. (time frame: 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2020.