Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02278133




Registration number
NCT02278133
Ethics application status
Date submitted
6/10/2014
Date registered
29/10/2014
Date last updated
9/10/2017

Titles & IDs
Public title
Study of WNT974 in Combination With LGX818 and Cetuximab in Patients With BRAF-mutant Metastatic Colorectal Cancer (mCRC) and Wnt Pathway Mutations
Scientific title
A Phase Ib/II Multi-center, Open Label, Dose Escalation Study of WNT974, LGX818 and Cetuximab in Patients With BRAFV600-mutant KRAS Wild-type Metastatic Colorectal Cancer Harboring Wnt Pathway Mutations
Secondary ID [1] 0 0
CWNT974X2102C
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: WNT974, LGX818 and cetuximab combo - Phase l: Dose Escalation phase; Phase ll: SIngle group assessing the triple combination of WNT974, LGX818 and cetuximab
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Dose Limiting Toxicities and exposure (AUC C1D15) to WNT974 and LGX818 (phase lb)
Timepoint [1] 0 0
12 months
Primary outcome [2] 0 0
Overall response rate in phase II
Timepoint [2] 0 0
30 months
Secondary outcome [1] 0 0
Overall response rate (ORR) (phase lb)
Timepoint [1] 0 0
36 months
Secondary outcome [2] 0 0
Overall survival (OS) (phase lb/ll)
Timepoint [2] 0 0
36 months
Secondary outcome [3] 0 0
Duration of response (DOR) (phase lb/ll)
Timepoint [3] 0 0
36 months
Secondary outcome [4] 0 0
Time to response (TTR) (phase lb/ll)
Timepoint [4] 0 0
36 months
Secondary outcome [5] 0 0
Progression free survival (PFS) (phase lb/ll)
Timepoint [5] 0 0
36 months
Secondary outcome [6] 0 0
Disease control rate (DCR) (phase lb/ll)
Timepoint [6] 0 0
36 months
Secondary outcome [7] 0 0
Plasma concentration of WNT974, LHA333, LGX818 (phase lb/ll)
Timepoint [7] 0 0
30 months
Secondary outcome [8] 0 0
Number of participants with Adverse Events as a measure of safety and tolerability (phase lb/ll)
Timepoint [8] 0 0
30 months
Secondary outcome [9] 0 0
Number of participants with Serious Adverse Events as a measure of safety and tolerability(phase lb/ll)
Timepoint [9] 0 0
30 months
Secondary outcome [10] 0 0
Biomarker activations for WNT and RTK-MAPK pathways (phase Ib/II)
Timepoint [10] 0 0
32 months
Secondary outcome [11] 0 0
Number of participants with dose interruptions and dose reductions (phase Ib/II)
Timepoint [11] 0 0
30 months

Eligibility
Key inclusion criteria
* Male or female aged = 18 years
* Histological or cytological confirmed metastatic colorectal cancer
* Written documentation of KRAS wild-type status and BRAFV600-mutation with RNF43 mutation and/or RSPO fusion
* Progression of disease after at least one prior standard of care regimen or intolerant to irinotecan based regimens
* Availability of a representative tumor specimen (primary or metastatic, archival or newly obtained)
* Measurable disease as per RECIST v1.1
* Eastern cooperative oncology group (ECOG) performance status = 2
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Phase II only: Prior treatment with RAF inhibitors, Wnt pathway inhibitors, cetuximab, panitumumab, and/or other EGFR inhibitors
* Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed to enroll
* Current treatment with medications or consuming foods that are strong inhibitors or inducers of CYP3A4/5 or herbal medications and that cannot be discontinued at least one week prior to the start of treatment.
* Symptomatic or untreated leptomeningeal disease
* Acute or chronic pancreatitis
* Clinically significant cardiac disease
* Patients with any of the following laboratory values at Screening/baseline

* Absolute neutrophil count (ANC) <1,500/mm3
* Platelets < 100,000/mm3
* Hemoglobin < 9.0 g/dL
* Serum creatinine >1.5 x ULN or calculated or directly measured CrCl < 50% lower limit of normal
* Serum total bilirubin >1.5 x ULN
* AST/SGOT and/or ALT/SGPT > 2.5 x ULN, (> 5 x ULN if liver metastases present)
* Patients with impaired hepatic function as defined by Childs-Pugh class B or C
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral WNT974/LGX818

Other protocol-defined inclusion/exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/06/2017
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Array BioPharma Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
South Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
United States of America
State/province [4] 0 0
Wisconsin
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Canada
State/province [7] 0 0
British Columbia
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
France
State/province [9] 0 0
Bordeaux
Country [10] 0 0
France
State/province [10] 0 0
Marseille
Country [11] 0 0
Israel
State/province [11] 0 0
Tel-Aviv
Country [12] 0 0
Italy
State/province [12] 0 0
MI
Country [13] 0 0
Netherlands
State/province [13] 0 0
Amsterdam
Country [14] 0 0
Singapore
State/province [14] 0 0
Singapore
Country [15] 0 0
Spain
State/province [15] 0 0
Catalunya
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Array BioPharma
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Clinical Trial Call Center
Address 0 0
Array BioPharma, Inc.
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

No information has been provided regarding IPD availability


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/NCT02278133