A Phase I Study of LXS196 in Patients With Metastatic Uveal Melanoma.

Uveal Melanoma Clinical Trial

Official title:

A Phase I, Multi-center, Open-label, Study of LXS196, an Oral Protein Kinase C Inhibitor, in Patients With Metastatic Uveal Melanoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02601378
• Other study ID #: CLXS196X2101
• Status: Terminated
• Phase: Phase 1
• Start date: February 1, 2016
• Est. completion date: January 7, 2022

Study information

• Verified date: September 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 107
• Est. completion date: January 7, 2022
• Est. primary completion date: January 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• 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:

• 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).

Related Conditions & MeSH terms

• Melanoma
• Uveal Melanoma
• Uveal Neoplasms

Intervention

Drug:
• LXS196
LXS196 as a single agent
• LXS196 and HDM201
LXS196 in combination with HDM201

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Westmead	New South Wales
France	Novartis Investigative Site	Paris
Netherlands	Novartis Investigative Site	Leiden
Norway	Novartis Investigative Site	Oslo
Spain	Novartis Investigative Site	Madrid
United States	Columbia University Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  France,  Netherlands,  Norway,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities (DLTs) (Dose escalation only)	cycle = 28 days	Cycle 1 in dose escalation
Primary	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)		Continuously throughout the study until 30 days after treatment discontinuation
Primary	Dose interruptions, reductions and dose intensity		Continuously throughout the study until 30 days after treatment discontinuation
Secondary	Overall response rate (ORR) per RECIST version 1.1 criteria		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	Plasma LXS196 concentration-time profiles as a single agent		Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	Modulation of signaling molecules downstream of PKC		Baseline and Cycle 1 Day 15
Secondary	Progression free survival (PFS) per RECIST version 1.1 criteria		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	Plasma PK parameters of LXS196 as a single agent:AUC		Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	Plasma PK parameters of LXS196 as a single agent: Cmax		Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	Plasma PK parameters of LXS196 as a single agent: Tmax		Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	Plasma PK parameters of LXS196 as a single agent: t1/2		Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	Plasma PK parameters of LXS196 as a single agent: Racc		Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	Plasma HDM201 concentration-time profiles		Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Secondary	Plasma PK parameters of HDM201: AUC		Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Secondary	Plasma PK parameters of HDM201: Cmax		Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Secondary	Plasma PK parameters of HDM201: Tmax		Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Secondary	Plasma PK parameters of HDM201: t1/2		Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Secondary	Plasma LXS196 concentration-time profiles in combination with HDM201		Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	Plasma PK parameters of LXS196 in combination with HDM201:AUC		Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	Plasma PK parameters of LXS196 in combination with HDM201: Cmax		Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	Plasma PK parameters of LXS196 in combination with HDM201: Tmax		Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	Plasma PK parameters of LXS196 in combination with HDM201: t1/2		Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	Plasma PK parameters of LXS196 in combination with HDM201: Racc		Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Secondary	LXS196 plasma protein binding as a single agent		Cycle 1 Day 1, 2, 15, 16
Secondary	LXS196 plasma protein content as a single agent		Cycle 1, 2, 3 and 4 Day 1

External Links

•   Study Results