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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02974725




Registration number
NCT02974725
Ethics application status
Date submitted
23/11/2016
Date registered
28/11/2016

Titles & IDs
Public title
A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma
Scientific 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
Secondary ID [1] 0 0
2016-004293-18
Secondary ID [2] 0 0
CLXH254X2102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
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
Number of participants with Adverse Events (AEs) as a measure of safety and tolerability
Timepoint [1] 0 0
up to 5 years
Primary outcome [2] 0 0
Dose limiting toxicities (DLTs) (dose escalation only)
Timepoint [2] 0 0
up to 3 years
Primary outcome [3] 0 0
Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions
Timepoint [3] 0 0
up to 5 years
Primary outcome [4] 0 0
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
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Overall Response Rate (ORR)
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Duration of response (DOR)
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Disease Control Rate (DCR)
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Progression Free Survival (PFS)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Overall Survival (OS) - (dose expansion part only)
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Derived PK parameter (Cmax) for LXH254 & LTT462:
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Derived PK parameter (AUC) for LXH254 & LTT462
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples
Timepoint [8] 0 0
up to 5 years
Secondary outcome [9] 0 0
Derived PK parameter (Cmax) for LXH254 & trametinib
Timepoint [9] 0 0
up to 5 years
Secondary outcome [10] 0 0
Derived PK parameter (AUC) for LXH254 & trametinib
Timepoint [10] 0 0
Up to 5 years
Secondary outcome [11] 0 0
Derived PK parameter (Cmax) for LXH254 & ribociclib
Timepoint [11] 0 0
Up to 5 years
Secondary outcome [12] 0 0
Derived PK parameter (AUC) for LXH254 & ribociclib
Timepoint [12] 0 0
Up to 5 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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. (Patients with KRAS mutant NSCLC with prior G12C inhibitor treatments are also excluded in the LXH254+trametinib expansion part). BRAF mutant patients group: Prior treatment with any EGFR, ALK, ROS1, KRAS, RAF (both BRAFV600 selective and pan-RAF), MEK1/2 and/or ERK1/2 inhibitors (for patients with BRAF V600 mutant NSCLC, prior treatments with BRAF and MEK1/2 inhibitors are allowed).

Patients who have received more than 3 lines of anti-cancer therapy are excluded.

* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/02/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/04/2024
Sample size
Target
Accrual to date
Final
241
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
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
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
France
State/province [7] 0 0
Lyon
Country [8] 0 0
France
State/province [8] 0 0
Paris 10
Country [9] 0 0
France
State/province [9] 0 0
Villejuif
Country [10] 0 0
Germany
State/province [10] 0 0
Dresden
Country [11] 0 0
Germany
State/province [11] 0 0
Essen
Country [12] 0 0
Germany
State/province [12] 0 0
Frankfurt
Country [13] 0 0
Germany
State/province [13] 0 0
Koeln
Country [14] 0 0
Israel
State/province [14] 0 0
Tel Aviv
Country [15] 0 0
Italy
State/province [15] 0 0
MI
Country [16] 0 0
Italy
State/province [16] 0 0
VR
Country [17] 0 0
Italy
State/province [17] 0 0
Napoli
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul
Country [19] 0 0
Poland
State/province [19] 0 0
Warszawa
Country [20] 0 0
Spain
State/province [20] 0 0
Andalucia
Country [21] 0 0
Spain
State/province [21] 0 0
Catalunya
Country [22] 0 0
Spain
State/province [22] 0 0
Comunidad Valenciana
Country [23] 0 0
Spain
State/province [23] 0 0
Navarra
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Sweden
State/province [25] 0 0
Stockholm

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
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
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)?
No
No/undecided IPD sharing reason/comment


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/NCT02974725