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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04417621




Registration number
NCT04417621
Ethics application status
Date submitted
3/06/2020
Date registered
4/06/2020

Titles & IDs
Public title
Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
Scientific title
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
Secondary ID [1] 0 0
2020-000873-26
Secondary ID [2] 0 0
CLXH254C12201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LXH254
Treatment: Drugs - LTT462
Treatment: Drugs - Trametinib
Treatment: Drugs - Ribociclib

Experimental: LXH254 + LTT462 -

Experimental: LXH254 + trametinib -

Experimental: LXH254 + ribociclib -


Treatment: Drugs: LXH254
LXH254 will be supplied as tablet for oral use.

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

Treatment: Drugs: Trametinib
Trametinib will be supplied as film-coated tablet for oral use

Treatment: Drugs: Ribociclib
Ribociclib will be supplied in tablets and hard gelatin capsules.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate
Timepoint [1] 0 0
35 months
Secondary outcome [1] 0 0
Duration of Reposnse (DOR)
Timepoint [1] 0 0
4 years
Secondary outcome [2] 0 0
Progression Free Survival (PFS)
Timepoint [2] 0 0
4 years
Secondary outcome [3] 0 0
Disease Control Rate (DCR)
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
4 years
Secondary outcome [5] 0 0
Derived PK parameter (Cmax) for LXH254 & LTT462
Timepoint [5] 0 0
Up to 5 months
Secondary outcome [6] 0 0
Derived PK parameter (Cmax) for LXH254 & trametinib
Timepoint [6] 0 0
Up to 5 months
Secondary outcome [7] 0 0
Derived PK parameter (Cmax) for LXH254 & ribociclib
Timepoint [7] 0 0
Up to 5 months
Secondary outcome [8] 0 0
Derived PK parameter (AUC) for LXH254 & LTT462
Timepoint [8] 0 0
Up to 5 months
Secondary outcome [9] 0 0
Derived PK parameter (AUC) for LXH254 & trametinib
Timepoint [9] 0 0
Up to 5 months
Secondary outcome [10] 0 0
Derived PK parameter (AUC) for LXH254 & ribociclib
Timepoint [10] 0 0
Up to 5 months
Secondary outcome [11] 0 0
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Timepoint [11] 0 0
35 months
Secondary outcome [12] 0 0
Dose Interruptions
Timepoint [12] 0 0
35 months
Secondary outcome [13] 0 0
Dose reductions
Timepoint [13] 0 0
35 months

Eligibility
Key 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.
Minimum age
12 Years
Maximum age
120 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2024
Actual
Sample size
Target
Accrual to date
Final
134
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - North Sydney
Recruitment hospital [2] 0 0
Novartis Investigative Site - Wooloongabba
Recruitment hospital [3] 0 0
Novartis Investigative Site - Subiaco
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
4102 - Wooloongabba
Recruitment postcode(s) [3] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Argentina
State/province [8] 0 0
Buenos Aires
Country [9] 0 0
Belgium
State/province [9] 0 0
Leuven
Country [10] 0 0
Belgium
State/province [10] 0 0
Wilrijk
Country [11] 0 0
France
State/province [11] 0 0
Lille
Country [12] 0 0
France
State/province [12] 0 0
Marseille
Country [13] 0 0
France
State/province [13] 0 0
Paris 10
Country [14] 0 0
France
State/province [14] 0 0
Pierre Benite
Country [15] 0 0
France
State/province [15] 0 0
Toulouse
Country [16] 0 0
France
State/province [16] 0 0
Villejuif
Country [17] 0 0
Germany
State/province [17] 0 0
Dresden
Country [18] 0 0
Germany
State/province [18] 0 0
Essen
Country [19] 0 0
Germany
State/province [19] 0 0
Heidelberg
Country [20] 0 0
Germany
State/province [20] 0 0
Tuebingen
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Italy
State/province [22] 0 0
MI
Country [23] 0 0
Italy
State/province [23] 0 0
Napoli
Country [24] 0 0
Netherlands
State/province [24] 0 0
Maastricht
Country [25] 0 0
Norway
State/province [25] 0 0
Oslo
Country [26] 0 0
Switzerland
State/province [26] 0 0
Lausanne
Country [27] 0 0
Switzerland
State/province [27] 0 0
Zuerich
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04417621