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Trial record 1 of 1 for:    CLXH254C12201
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Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04417621
Recruitment Status : Recruiting
First Posted : June 4, 2020
Last Update Posted : May 19, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE June 3, 2020
First Posted Date  ICMJE June 4, 2020
Last Update Posted Date May 19, 2022
Actual Study Start Date  ICMJE October 30, 2020
Estimated Primary Completion Date August 3, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2020)
Overall Response Rate [ Time Frame: 35 months ]
Confirmed ORR using RECIST v1.1, per local assessment
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2020)
  • Duration of Reposnse (DOR) [ Time Frame: 4 years ]
    Local and central assessment
  • Progression Free Survival (PFS) [ Time Frame: 4 years ]
  • Disease Control Rate (DCR) [ Time Frame: 3 years ]
    Using RECIST v1.1, per local and central assessment
  • Overall Survival (OS) [ Time Frame: 4 years ]
  • Derived PK parameter (Cmax) for LXH254 & LTT462 [ Time Frame: Up to 5 months ]
  • Derived PK parameter (Cmax) for LXH254 & trametinib [ Time Frame: Up to 5 months ]
  • Derived PK parameter (Cmax) for LXH254 & ribociclib [ Time Frame: Up to 5 months ]
  • Derived PK parameter (AUC) for LXH254 & LTT462 [ Time Frame: Up to 5 months ]
  • Derived PK parameter (AUC) for LXH254 & trametinib [ Time Frame: Up to 5 months ]
  • Derived PK parameter (AUC) for LXH254 & ribociclib [ Time Frame: Up to 5 months ]
  • Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 35 months ]
    Number of participants with Adverse Events (AEs) and SAEs as a measure of safety and tolerability
  • Dose Interruptions [ Time Frame: 35 months ]
    Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions
  • Dose reductions [ Time Frame: 35 months ]
    Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
Official Title  ICMJE A Randomized, Open-label, Multi-arm, Two-part, Phase II Study to Assess Efficacy and Safety of Multiple LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic BRAFV600 or NRAS Mutant Melanoma
Brief Summary The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in previously treated unresectable or metastatic melanoma
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE
  • Drug: LXH254
    LXH254 will be supplied as tablet for oral use.
  • Drug: LTT462
    LTT462 will be supplied as hard gelatin capsule for oral use.
  • Drug: Trametinib
    Trametinib will be supplied as film-coated tablet for oral use
  • Drug: Ribociclib
    Ribociclib will be supplied in tablets and hard gelatin capsules.
Study Arms  ICMJE
  • Experimental: LXH254 + LTT462
    Interventions:
    • Drug: LXH254
    • Drug: LTT462
  • Experimental: LXH254 + trametinib
    Intervention: Drug: Trametinib
  • Experimental: LXH254 + ribociclib
    Intervention: Drug: Ribociclib
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 3, 2020)
320
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 14, 2022
Estimated Primary Completion Date August 3, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Male or female must be ≥ 12 years For adolescents only (12-17 years): body weight > 40kg Histologically confirmed unresectable or metastatic cutaneous melanoma

Previously treated for unresectable or metastatic melanoma:

  • Participants with NRAS mutation:
  • Participants must have received prior systemic therapy for unresectable or metastatic melanoma with checkpoint inhibitors (CPI), either an anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents.
  • A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents administered with CPI are permitted.
  • To rule out pseudo-progression, participants must have documented confirmed progressive disease as per RECIST v1.1 while on/after treatment with checkpoint inhibitor therapy. Confirmation is not required for patients who remained on treatment for >6 months.
  • Participants with BRAFV600 mutant disease:
  • Participants must have received prior systemic therapy for unresectable or metastatic melanoma with checkpoint inhibitors (CPI), either an anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents. Additionally, participants must have received targeted therapy with a RAFi as a single agent or in combination with a MEKi (+/- CPI allowed) as the last prior therapy.
  • A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents with CPI are permitted.
  • A maximum of one line of targeted therapy is allowed, and it must be the most recent line of therapy.
  • Participants must have documented progressive disease as per RECIST v1.1 while on/after treatment with targeted therapy.

Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:

  • ≤ 4 weeks for radiation therapy or ≤ 2 weeks for limited field radiation for palliation prior to the first dose of study treatment.
  • ≤ 2 weeks for small molecule therapeutics.
  • ≤ 4 weeks for any immunotherapy treatment including immune checkpoint inhibitors.
  • ≤ 4 weeks for chemotherapy agents, locally directed anti-neoplastic agents, or other investigational agents.
  • ≤ 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea and mitomycin c.

Participants participating in additional parallel investigational drug or medical device studies.

All primary central nervous system (CNS) tumors or symptomatic CNS metastases that are neurologically unstable History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).

Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

Other protocol-defined exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 120 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   France,   Germany,   Israel,   Italy,   Netherlands,   Norway,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04417621
Other Study ID Numbers  ICMJE CLXH254C12201
2020-000873-26 ( EudraCT Number )
Has Data Monitoring Committee Yes
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: Yes
Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date May 2022

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