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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02601378
Recruitment Status : Active, not recruiting
First Posted : November 10, 2015
Last Update Posted : August 5, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE November 6, 2015
First Posted Date  ICMJE November 10, 2015
Last Update Posted Date August 5, 2020
Actual Study Start Date  ICMJE February 1, 2016
Estimated Primary Completion Date June 29, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 23, 2015)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 6, 2015)
  • 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: Continously throughtout the study until 30 days after treatment discontinutation ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2017)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2015)
  • 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 [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]
  • Modulation of signaling molecules downstream of protein kinase C inhibitor [ 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:AUC [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]
  • Plasma PK parameters of LXS196: Cmax [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]
  • Plasma PK parameters of LXS196: Tmax [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]
  • Plasma PK parameters of LXS196: t1/2 [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]
  • Plasma PK parameters of LXS196: Racc [ Time Frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I Study of LXS196 in Patients With Metastatic Uveal Melanoma.
Official Title  ICMJE A Phase I, Multi-center, Open-label, Study of LXS196, an Oral Protein Kinase C Inhibitor, in Patients With Metastatic Uveal Melanoma
Brief Summary This study is 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Uveal Melanoma
Intervention  ICMJE
  • Drug: LXS196
    LXS196 as a single agent
  • Drug: LXS196 and HDM201
    LXS196 in combination with HDM201
Study Arms  ICMJE
  • Experimental: LXS196 as a single agent
    About 68 patients will be enrolled in dose escalation and expansion
    Intervention: Drug: LXS196
  • Experimental: LXS196 in combination with HDM201
    about 44 patients to be enrolled in dose escalation and expansion
    Intervention: Drug: LXS196 and HDM201
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 20, 2019)
107
Original Estimated Enrollment  ICMJE
 (submitted: November 6, 2015)
53
Estimated Study Completion Date  ICMJE June 30, 2021
Estimated Primary Completion Date June 29, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Netherlands,   Norway,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02601378
Other Study ID Numbers  ICMJE CLXS196X2101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP