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

NCT02601378 | Terminated Phase 1 FDA Drug

• 1 other identifier: CLXS196X2101
• Study Type: interventional
• Target: 107
• Locations: 6 countries
• Sites: 6

Brief 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.

Conditions

Uveal Melanoma

Keywords

Uveal melanoma; Metastatic uveal melanoma; Phase I; LXS196; PKC inhibitor; HDM201; HDM2 inhibitor; dose escalation

Outcome Measures

Primary Outcomes (3)

• Incidence of dose limiting toxicities (DLTs) (Dose escalation only)

  cycle = 28 days

  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)

  Continuously throughout the study until 30 days after treatment discontinuation

• Dose interruptions, reductions and dose intensity

  Continuously throughout the study until 30 days after treatment discontinuation

Secondary Outcomes (22)

• 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

• Plasma LXS196 concentration-time profiles as a single agent

  Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1

• Modulation of signaling molecules downstream of PKC

  Baseline and Cycle 1 Day 15

• 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

• 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

Study Arms (2)

LXS196 as a single agent

EXPERIMENTAL

About 68 patients will be enrolled in dose escalation and expansion

Drug: LXS196

LXS196 in combination with HDM201

EXPERIMENTAL

about 44 patients to be enrolled in dose escalation and expansion

Drug: LXS196 and HDM201

Interventions

LXS196 DRUG

LXS196 as a single agent

LXS196 as a single agent

LXS196 and HDM201 DRUG

LXS196 in combination with HDM201

LXS196 in combination with HDM201

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

Location

Novartis Investigative Site

Paris, 75231, France

Location

Novartis Investigative Site

Leiden, 2300 RC, Netherlands

Location

Novartis Investigative Site

Oslo, 0379, Norway

Location

Novartis Investigative Site

Madrid, 28050, Spain

Location

Related Links

• Study Results

MeSH Terms

Conditions

Uveal Melanoma

Interventions

siremadlin

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2015
• First Posted: November 10, 2015
• Study Start: February 1, 2016
• Primary Completion: January 7, 2022
• Study Completion: January 7, 2022
• Last Updated: September 29, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); FR (1); US (1); ES (1); NO (1); AU (1)