Uveal MelanomaPhase 1NCT02601378
A Phase I Study of LXS196 in Patients With Metastatic Uveal Melanoma.
A Phase 1 study testing LXS196 and LXS196 and HDM201 in people with Uveal Melanoma, run by Novartis Pharmaceuticals at 6 sites in 6 countries.
Trial summary
This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of LXS196 as a single agent and in combination with HDM201 in patients with metastatic uveal melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveal Melanoma
- What is being tested?
- LXS196 and LXS196 and HDM201
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 6 sitesin 6 countries
- Study dates
- 1 Feb 2016to 7 Jan 2022
- 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
- Male or female patients ≥18 years of age
- Diagnosis of uveal melanoma with histological or cytological confirmed metastatic disease. Disease must be treatment naive or have progressed (radiologically or clinically) on most recent therapy.
- Willingness to provide newly obtained tumor tissue at baseline and on treatment unless contraindicated by medical risk in the opinion of the treating physician.
- Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as >10 mm with CT scan.
- ECOG performance status ≤ 1
Who cannot join
- Malignant disease other than that being treated in this study.
- Symptomatic or untreated CNS metastases or spinal cord compression. Brain metastasis must be stable with verification by imaging .
- Impaired cardiac function or clinically significant cardiac diseases
- History of thromboembolic or cerebrovascular events within the last 6 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism (applicable to combination part only).
- Patients who are receiving treatment with medications that cannot be discontinued prior to study entry and that are considered to be any of the following:
- known and possible risk for QT prolongation
Show all 18Show fewer
- known to be strong inducers or inhibitors of CYP3A4/5 (for single agent part); known to be moderate to strong inducers or inhibitors of CYP3A4/5 (for combination part)
- known to be inducers or inhibitors of P-gp
- known to be substrates of CYP3A4/5 and P-gp with a narrow therapeutic index
- Patients with abnormal laboratory values, defined as any of the following:
- AST or ALT > 3 times ULN, AST or ALT > 5 times ULN for patients with liver metastases.
- Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN.
- Absolute neutrophil count (ANC) ≤ 1.5 x109/L.
- Platelets ≤ 100 x 109/L.
- Hemoglobin (Hgb) ≤ 90 g/L (9 g/dL).
- Creatinine > 1.5 x ULN
- Patients receiving live vaccines due to the expected bone marrow toxicity (applicable to combination part only).
- Patients treated with growth factors targeting the myeloid lineage (e.g. G-CSF, GM-CSF and M-CSF) within 2 weeks of starting study treatment. (applicable to combination part only).
Trial locations and contacts
6 sites in 6 countries.
6 sites in 6 countries
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: A Phase I, Multi-center, Open-label, Study of LXS196, an Oral Protein Kinase C Inhibitor, in Patients With Metastatic Uveal Melanoma
This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of LXS196 as a single agent and in combination with HDM201 in patients with metastatic uveal melanoma.
- Conditions
- Uveal Melanoma
- Being tested
- LXS196, LXS196 and HDM201
- Keywords
- Uveal melanoma, Metastatic uveal melanoma, Phase I, LXS196, PKC inhibitor, HDM201, HDM2 inhibitor, dose escalation
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LXS196Drug
LXS196 as a single agent
LXS196 and HDM201Drug
LXS196 in combination with HDM201
| Study group | Role | What they receive |
|---|---|---|
| LXS196 as a single agent | Experimental | About 68 patients will be enrolled in dose escalation and expansion Receives: Drug: LXS196 |
| LXS196 in combination with HDM201 | Experimental | about 44 patients to be enrolled in dose escalation and expansion Receives: Drug: LXS196 and HDM201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicities (DLTs) (Dose escalation only)
cycle = 28 days
Measured: Cycle 1 in dose escalation
Incidence and severity of adverse events and serious adverse events, including changes in laboratory parameters, vital signs and ECGs graded as per NCI CTCAE version 4.03 (All patients)
Measured: Continuously throughout the study until 30 days after treatment discontinuation
Dose interruptions, reductions and dose intensity
Measured: Continuously throughout the study until 30 days after treatment discontinuation
Secondary outcomes (22)
Overall response rate (ORR) per RECIST version 1.1 criteria
Measured: From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months
Plasma LXS196 concentration-time profiles as a single agent
Measured: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Modulation of signaling molecules downstream of PKC
Measured: Baseline and Cycle 1 Day 15
Progression free survival (PFS) per RECIST version 1.1 criteria
Measured: From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months
Plasma PK parameters of LXS196 as a single agent:AUC
Measured: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Cmax
Measured: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Tmax
Measured: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: t1/2
Measured: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Racc
Measured: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma HDM201 concentration-time profiles
Measured: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: AUC
Measured: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: Cmax
Measured: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: Tmax
Measured: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: t1/2
Measured: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma LXS196 concentration-time profiles in combination with HDM201
Measured: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201:AUC
Measured: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Cmax
Measured: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Tmax
Measured: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: t1/2
Measured: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Racc
Measured: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
LXS196 plasma protein binding as a single agent
Measured: Cycle 1 Day 1, 2, 15, 16
LXS196 plasma protein content as a single agent
Measured: Cycle 1, 2, 3 and 4 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2015 (estimated)
- Study start1 Feb 2016
- Primary completion7 Jan 2022
- Study completion7 Jan 2022
Why it stopped: The combination part of the study was terminated early due to business reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uveal MelanomaStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 107 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
- NCT02601378
- Sponsor's protocol ID
- CLXS196X2101
- Status last verified
- Sep 2022
- First submitted
- 6 Nov 2015
- Last updated
- 29 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Multi-center, Open-label, Study of LXS196, an Oral Protein Kinase C Inhibitor, in Patients With Metastatic Uveal Melanoma
- ClinicalTrials.gov ID
- NCT02601378
- Acronym / sponsor ID
- CLXS196X2101
- Conditions
- Uveal Melanoma
- Keywords
- Uveal melanoma, Metastatic uveal melanoma, Phase I, LXS196, PKC inhibitor, HDM201, HDM2 inhibitor, dose escalation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The combination part of the study was terminated early due to business reasons
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 Feb 2016 (actual)
- Primary completion
- 7 Jan 2022 (actual)
- Study completion
- 7 Jan 2022 (actual)
- First posted
- 10 Nov 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.
This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of LXS196 as a single agent and in combination with HDM201 in patients with metastatic uveal melanoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LXS196 as a single agent | Experimental | Drug: LXS196About 68 patients will be enrolled in dose escalation and expansion |
| LXS196 in combination with HDM201 | Experimental | Drug: LXS196 and HDM201about 44 patients to be enrolled in dose escalation and expansion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female patients ≥18 years of age
- Diagnosis of uveal melanoma with histological or cytological confirmed metastatic disease. Disease must be treatment naive or have progressed (radiologically or clinically) on most recent therapy.
- Willingness to provide newly obtained tumor tissue at baseline and on treatment unless contraindicated by medical risk in the opinion of the treating physician.
- Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as >10 mm with CT scan.
- ECOG performance status ≤ 1
Key exclusion criteria (18 listed)
- Malignant disease other than that being treated in this study.
- Symptomatic or untreated CNS metastases or spinal cord compression. Brain metastasis must be stable with verification by imaging .
- Impaired cardiac function or clinically significant cardiac diseases
- History of thromboembolic or cerebrovascular events within the last 6 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism (applicable to combination part only).
- Patients who are receiving treatment with medications that cannot be discontinued prior to study entry and that are considered to be any of the following:
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 |
|---|---|---|
| LXS196LXS196 as a single agent | Drug | LXS196 as a single agent |
| LXS196 and HDM201LXS196 in combination with HDM201 | Drug | LXS196 in combination with HDM201 |
Primary outcome
Incidence of dose limiting toxicities (DLTs) (Dose escalation only)
Time frame: Cycle 1 in dose escalation
cycle = 28 days
Incidence and severity of adverse events and serious adverse events, including changes in laboratory parameters, vital signs and ECGs graded as per NCI CTCAE version 4.03 (All patients)
Time frame: Continuously throughout the study until 30 days after treatment discontinuation
Dose interruptions, reductions and dose intensity
Time frame: Continuously throughout the study until 30 days after treatment discontinuation
22 secondary outcomes
Overall response rate (ORR) per RECIST version 1.1 criteria
Time frame: From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months
Plasma LXS196 concentration-time profiles as a single agent
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Modulation of signaling molecules downstream of PKC
Time frame: Baseline and Cycle 1 Day 15
Progression free survival (PFS) per RECIST version 1.1 criteria
Time frame: From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months
Plasma PK parameters of LXS196 as a single agent:AUC
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Cmax
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Tmax
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: t1/2
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Racc
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma HDM201 concentration-time profiles
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: AUC
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: Cmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: Tmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: t1/2
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma LXS196 concentration-time profiles in combination with HDM201
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201:AUC
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Cmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Tmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: t1/2
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Racc
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
LXS196 plasma protein binding as a single agent
Time frame: Cycle 1 Day 1, 2, 15, 16
LXS196 plasma protein content as a single agent
Time frame: Cycle 1, 2, 3 and 4 Day 1
Results and safety
The study was stopped early (reason given: The combination part of the study was terminated early due to business reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2022.
- Study ResultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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
6 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 LXS196 and LXS196 and HDM201 in people with Uveal Melanoma, run by Novartis Pharmaceuticals at 6 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 5 inclusion and 18 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: stopped early, as of the sponsor's last update on 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Australia, France, Netherlands, Norway 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 was stopped early (reason given: The combination part of the study was terminated early due to business reasons). Results are not available in the source record.
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?
Incidence of dose limiting toxicities (DLTs) (Dose escalation only) (time frame: Cycle 1 in dose escalation). 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 29 Sep 2022; AzTrials last refreshed its copy on 26 Oct 2026.