Study of WNT974 in Combination With LGX818 and Cetuximab in Patients With BRAF-mutant Metastatic Colorectal Cancer (mCRC) and Wnt Pathway Mutations

Completed · Phase 1/Phase 2

Conditions studied: Metastatic Colorectal Cancer

In brief

The purpose of this study is to assess the safety and anti-tumor activity of the triple combination of WNT974, LGX818 and cetuximab in BRAFV600-mutant mCRC with RNF43 mutations or RSPO fusions. The design of this study is based upon the translational and pre-clinical data that suggest that Wnt pathway signals, increased due to RNF43 mutations or RSPO fusions, cooperate with the EGFR and BRAF signals to maintain the growth of BRAFV600 CRCs. Inhibition of these signals with the triple combination of WNT974, LGX818 and cetuximab may result in anti-tumor activity.

Key facts

Study ID

NCT02278133

Run by

Array BioPharma

People needed

20

Starts

2014-12-01

Expected to finish

2017-06-23

Last updated by the study team

2017-10-09

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• 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

Where it is running

• Memorial Sloan-Kettering Cancer Center (MSKCC) MSKCC (3) — New York, New York, United States
• Medical University of South Carolina Oncology Dept — Charleston, South Carolina, United States
• University of Texas/MD Anderson Cancer Center Onc. Dept, — Houston, Texas, United States
• University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc — Madison, Wisconsin, United States
• Array BioPharma Investigative Site — Parkville, Victoria, Australia
• Array BioPharma Investigative Site — Leuven, Belgium
• Array BioPharma Investigative Site — Edmonton, Alberta, Canada
• Array BioPharma Investigative Site — Vancouver, British Columbia, Canada
• Array BioPharma Investigative Site — Toronto, Ontario, Canada
• Array BioPharma Investigative Site — Bordeaux, France
• Array BioPharma Investigative Site — Marseille, France
• Array BioPharma Investigative Site — Tel Aviv, Israel
• Array BioPharma Investigative Site — Milan, MI, Italy
• Array BioPharma Investigative Site — Amsterdam, Netherlands
• Array BioPharma Investigative Site — Singapore, Singapore
• Array BioPharma Investigative Site — Barcelona, Catalonia, Spain
• Array BioPharma Investigative Site — L'Hospitalet de Llobregat, Catalonia, Spain
• Array BioPharma Investigative Site — Madrid, Spain
• Array BioPharma Investigative Site — Madrid, Spain

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.