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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02601378




Registration number
NCT02601378
Ethics application status
Date submitted
6/11/2015
Date registered
10/11/2015

Titles & IDs
Public title
A Phase I Study of LXS196 in Patients With Metastatic Uveal Melanoma.
Scientific title
A Phase I, Multi-center, Open-label, Study of LXS196, an Oral Protein Kinase C Inhibitor, in Patients With Metastatic Uveal Melanoma
Secondary ID [1] 0 0
CLXS196X2101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Uveal Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Other cancer types
Eye 0 0 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LXS196
Treatment: Drugs - LXS196 and HDM201

Experimental: LXS196 as a single agent - About 68 patients will be enrolled in dose escalation and expansion

Experimental: LXS196 in combination with HDM201 - about 44 patients to be enrolled in dose escalation and expansion


Treatment: Drugs: LXS196
LXS196 as a single agent

Treatment: Drugs: LXS196 and HDM201
LXS196 in combination with HDM201
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities (DLTs) (Dose escalation only)
Timepoint [1] 0 0
Cycle 1 in dose escalation
Primary outcome [2] 0 0
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)
Timepoint [2] 0 0
Continuously throughout the study until 30 days after treatment discontinuation
Primary outcome [3] 0 0
Dose interruptions, reductions and dose intensity
Timepoint [3] 0 0
Continuously throughout the study until 30 days after treatment discontinuation
Secondary outcome [1] 0 0
Overall response rate (ORR) per RECIST version 1.1 criteria
Timepoint [1] 0 0
From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months
Secondary outcome [2] 0 0
Plasma LXS196 concentration-time profiles as a single agent
Timepoint [2] 0 0
Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [3] 0 0
Modulation of signaling molecules downstream of PKC
Timepoint [3] 0 0
Baseline and Cycle 1 Day 15
Secondary outcome [4] 0 0
Progression free survival (PFS) per RECIST version 1.1 criteria
Timepoint [4] 0 0
From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months
Secondary outcome [5] 0 0
Plasma PK parameters of LXS196 as a single agent:AUC
Timepoint [5] 0 0
Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [6] 0 0
Plasma PK parameters of LXS196 as a single agent: Cmax
Timepoint [6] 0 0
Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [7] 0 0
Plasma PK parameters of LXS196 as a single agent: Tmax
Timepoint [7] 0 0
Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [8] 0 0
Plasma PK parameters of LXS196 as a single agent: t1/2
Timepoint [8] 0 0
Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [9] 0 0
Plasma PK parameters of LXS196 as a single agent: Racc
Timepoint [9] 0 0
Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [10] 0 0
Plasma HDM201 concentration-time profiles
Timepoint [10] 0 0
Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Secondary outcome [11] 0 0
Plasma PK parameters of HDM201: AUC
Timepoint [11] 0 0
Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Secondary outcome [12] 0 0
Plasma PK parameters of HDM201: Cmax
Timepoint [12] 0 0
Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Secondary outcome [13] 0 0
Plasma PK parameters of HDM201: Tmax
Timepoint [13] 0 0
Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Secondary outcome [14] 0 0
Plasma PK parameters of HDM201: t1/2
Timepoint [14] 0 0
Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Secondary outcome [15] 0 0
Plasma LXS196 concentration-time profiles in combination with HDM201
Timepoint [15] 0 0
Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [16] 0 0
Plasma PK parameters of LXS196 in combination with HDM201:AUC
Timepoint [16] 0 0
Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [17] 0 0
Plasma PK parameters of LXS196 in combination with HDM201: Cmax
Timepoint [17] 0 0
Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [18] 0 0
Plasma PK parameters of LXS196 in combination with HDM201: Tmax
Timepoint [18] 0 0
Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [19] 0 0
Plasma PK parameters of LXS196 in combination with HDM201: t1/2
Timepoint [19] 0 0
Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [20] 0 0
Plasma PK parameters of LXS196 in combination with HDM201: Racc
Timepoint [20] 0 0
Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary outcome [21] 0 0
LXS196 plasma protein binding as a single agent
Timepoint [21] 0 0
Cycle 1 Day 1, 2, 15, 16
Secondary outcome [22] 0 0
LXS196 plasma protein content as a single agent
Timepoint [22] 0 0
Cycle 1, 2, 3 and 4 Day 1

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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
* 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/01/2022
Sample size
Target
Accrual to date
Final
107
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
France
State/province [2] 0 0
Paris
Country [3] 0 0
Netherlands
State/province [3] 0 0
Leiden
Country [4] 0 0
Norway
State/province [4] 0 0
Oslo
Country [5] 0 0
Spain
State/province [5] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02601378