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A Phase Ib Study of LXH254-centric Combinations in NSCLC or 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: NCT02974725
Recruitment Status : Recruiting
First Posted : November 28, 2016
Last Update Posted : August 5, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Melanoma Drug: LXH254 Drug: LTT462 Drug: Trametinib Drug: Ribociclib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 315 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-label, Multicenter Study of Oral LXH254-centric Combinations in Adult Patients With Advanced or Metastatic KRAS or BRAF Mutant Non-Small Cell Lung Cancer or NRAS Mutant Melanoma
Actual Study Start Date : February 24, 2017
Estimated Primary Completion Date : January 11, 2022
Estimated Study Completion Date : January 11, 2022


Arm Intervention/treatment
Experimental: LXH254+LTT462 Drug: LXH254
LXH254 will be supplied as tablet for oral use.

Drug: LTT462
LTT462 will be supplied as hard gelatin capsule for oral use.

Experimental: LXH254+Trametinib Drug: Trametinib
Trametinib will be supplied as film-coated tablet for oral use

Drug: LXH254
Trametinib will be supplied as film-coated tablet for oral use

Experimental: LXH254+Ribociclib Drug: Ribociclib
Ribociclib will be supplied in tablets and hard gelatin capsules.




Primary Outcome Measures :
  1. Number of participants with Adverse Events (AEs) as a measure of safety and tolerability [ Time Frame: up to 5 years ]
  2. Dose limiting toxicities (DLTs) (dose escalation only) [ Time Frame: up to 3 years ]
  3. Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions [ Time Frame: up to 5 years ]
  4. Tolerability measured by the dose intensity of study drug, Relative Dose intensity for subjects with non-zero duration of exposure is computed as the ratio of dose intensity and planned dose intentity [ Time Frame: Up to 5 years ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to 5 years ]
  2. Duration of response (DOR) [ Time Frame: Up to 5 years ]
  3. Disease Control Rate (DCR) [ Time Frame: Up to 5 years ]
  4. Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
  5. Overall Survival (OS) - (dose expansion part only) [ Time Frame: Up to 6 years ]
  6. Derived PK parameter (Cmax) for LXH254 & LTT462: [ Time Frame: Up to 5 years ]
  7. Derived PK parameter (AUC) for LXH254 & LTT462 [ Time Frame: Up to 5 years ]
  8. Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples [ Time Frame: up to 5 years ]
  9. Derived PK parameter (Cmax) for LXH254 & trametinib [ Time Frame: up to 5 years ]
  10. Derived PK parameter (AUC) for LXH254 & trametinib [ Time Frame: Up to 5 years ]
  11. Derived PK parameter (Cmax) for LXH254 & ribociclib [ Time Frame: Up to 5 years ]
  12. Derived PK parameter (AUC) for LXH254 & ribociclib [ Time Frame: Up to 5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have advanced or metastatic NSCLC or cutaneous melanoma
  • Presence of KRAS or BRAF mutation (NSCLC) or NRAS mutation (cutaneous melanoma) in tumor tissue
  • All patients participating in this clinical trial must have progressed following standard therapy or, in the opinion of the Investigator, no effective standard therapy exists, is tolerated, appropriate or is considered equivalent to study treatment.
  • ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2

Exclusion Criteria:

  • Dose expansion - KRAS or NRAS mutant patients groups: Prior treatment with a RAFi (including any BRAFi and pan-RAFi), MEKi and/or ERKi. BRAF mutant patients group: Prior treatment with an ERKi and/or a pan-RAFi.
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
  • 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.
  • Patients receiving proton pump inhibitors (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
  • Patients with Gilbert's syndrome or other heritable diseases of bile processing.

Other protocol-defined inclusion/exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02974725


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, California
University of California San Diego Recruiting
San Diego, California, United States, 92103
Contact    858-657-8530      
Principal Investigator: Mina Nikanjam         
UCSF Medical Center Recruiting
San Francisco, California, United States, 94143
Contact: Michael Wong    415-353-1351    Michael.Wong2@ucsf.edu   
Principal Investigator: Adil Daud         
United States, Massachusetts
Massachusetts General Hospital SC Recruiting
Boston, Massachusetts, United States, 02114
Contact: Gianluca Diubaldi    617-726-1849    gianluca_diubaldi@dfci.harvard.edu   
Principal Investigator: Rebecca Heist         
United States, Tennessee
Sarah Cannon Research Institute Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Nicole Piechuta    +1 615 329 7274    Nicole.Shoviak@SarahCannon.com   
Principal Investigator: Meredith Ann McKean         
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3000
Novartis Investigative Site Recruiting
Prahran, Victoria, Australia, 3181
Belgium
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
France
Novartis Investigative Site Recruiting
Paris Cedex 10, France, 75475
Novartis Investigative Site Recruiting
Villejuif Cedex, France, 94800
Germany
Novartis Investigative Site Recruiting
Dresden, Germany, 01307
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Novartis Investigative Site Recruiting
Frankfurt, Germany, 60590
Novartis Investigative Site Recruiting
Koeln, Germany, 50937
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Novartis Investigative Site Recruiting
Napoli, Italy, 80131
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 03080
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 06351
Poland
Novartis Investigative Site Recruiting
Warszawa, Poland, 02 781
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site Recruiting
Pamplona, Navarra, Spain, 31008
Novartis Investigative Site Recruiting
Barcelona, Spain, 08035
Novartis Investigative Site Recruiting
Madrid, Spain, 28034
Sweden
Novartis Investigative Site Recruiting
Stockholm, Sweden, 171 76
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02974725    
Other Study ID Numbers: CLXH254X2102
2016-004293-18 ( EudraCT Number )
First Posted: November 28, 2016    Key Record Dates
Last Update Posted: August 5, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
NSCLC
Melanoma
NRAS
KRAS
BRAF
LXH254
LTT462
Trametinib
Ribocliclib
Non-small cell lung carcinoma (NSCLC)
treatment of lung cancer after first metastasis
lung cancer
lung adenocarcinoma
Large-cell lung carcinoma
Non small cell lung carcinoma
Non small cell lung cancer
Large cell lung carcinoma
Large cell lung cancer
squamous cell lung carcinoma
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Melanoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Trametinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action