colorectal cancer MedDRA version: 20.0 Level: HLT Classification code 10010023 Term: Colorectal neoplasms malignant System Organ Class: 100000005080
Conditions
Interventions
Product Code: WNT974
Pharmaceutical Form: Capsule, hard
Current Sponsor code: WNT974
Other descriptive name: LGK974
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number:
Sponsors
Array BioPharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 27 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: Phase II only: Prior treatment with RAF inhibitors, Wnt pathway inhibitors, cetuximab, panitumumab, and/or other EGFR inhibitors. Note: Further enrollment to the study has been discontinued as of 21 March 2016. Therefore, references to phase II study design and objectives are no longer relevant. 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) 1.5 x ULN or calculated or directly measured CrCl 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 Child-Pugh class B or C. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral WNT974/LGX818.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase Ib: To estimate the MTD(s) and/or RP2D(s) of the triple combination of WNT974, LGX818 and cetuximab in patients with BRAFV600-mutant CRC harboring upstream Wnt pathway mutations. Phase II: To estimate the preliminary anti-tumor activity of the RP2D(s) of WNT974 in combination with LGX818 and cetuximab in patients with BRAFV600-mutant CRC harboring upstream Wnt pathway mutations Note: Further enrollment to the study has been discontinued as of 21 March 2016. Therefore, references to phase II study design and objectives are no longer relevant.;Secondary Objective: To assess additional parameters of clinical activity of WNT974 in combination with LGX818 and cetuximab in BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation. Phase Ib/II: To characterize the safety and tolerability of WNT974 in combination with LGX818 and cetuximab in patients with BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation Phase Ib/II: To characterize the pharmacokinetics (PK) of WNT974, its pharmacologically active metabolite LHA333, and LGX818 when used in combination therapy with cetuximab Phase Ib/II: To assess the pharmacodynamic effect of WNT974, LGX818 in combination with cetuximab and a potential relationship with clinical outcome (ORR) ;Primary end point(s): 1. Phase Ib: To estimate the MTD(s)/RP2D(s) of the triple combination of WNT974, LGX818 and cetuximab in patients with BRAFV600-mutant, KRAS wild-type (WT) mCRC harboring upstream Wnt pathway mutations, as measured by incidence of dose-limiting toxicities (DLTs) and exposure to WNT974 and LGX818 as measured by PK parameters. 2. Phase II: To estimate the preliminary anti-tumor activity at the RP2D(s) of the combination of WNT974, LGX818 and cetuximab, in patients with BRAFV600-mutant metastatic colorectal cancer harboring upstream Wnt pathway mutations, based on the Overall Response Rate (ORR). Note: Further enrollment to the study has been discontinued as of 21 March 2016. Th | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To characterize the safety and tolerability of WNT974 in combination with LGX818 and cetuximab in patients with BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation, as assessed by the incidence and severity of adverse events. 2. To characterize the pharmacokinetics (PK) of WNT974, its pharmacologically active metabolite, LHA333, and LGX818 when used in combination therapy with cetuximab, as measured by plasma concentration. 3. To determine pharmacodynamic (PD) profile of WNT974, in combination with LGX818 and cetuximab in patients with BRAFV600-mutant mCRC and potential relationship with clinical outcome, as measured by biomarkers of activation for Wnt and RTK-MAPK pathways. 4. To assess additional parameters of clinical activity of WNT974 in combination with LGX818 and cetuximab in BRAFV600-mutant mCRC with evidence of upstream Wnt pathway activation ;Timepoint(s) of evaluation of this end point: Time evaluation secondary Endpoint 1 = 30 months Time evaluation seconday Endpoint 2 = 30 months Time evaluation secondary Endpoint 3 =32 months Time evaluation secondary Endpoint 4 =36 months | — |
Countries
Belgium, France, Italy, Netherlands, Spain, United Kingdom
Contacts
Public ContactMargaret Vargo
Array BioPharma Inc.
Outcome results
None listed