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

Recruiting

Conditions: colorectal cancer
cancer of the intestine
10017991

Registration Number: NL-OMON45070

Lead Sponsor: Array Biopharma

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 4

Inclusion Criteria

• Histological or cytological confirmed metastatic colorectal cancer.
• Written documentation of KRAS-wild-type status and BRAFV600 mutation with RNF43 mutations and/or RSPO fusions. See protocol page 37 for details.
• Progression of disease after at least one prior standard of care regimen or intolerance to irinotecan based regimens. See protocol page 37 for details.
• Measurable disease.
• ECOG performance status 0, 1, 2.

Exclusion Criteria

• Phase II only: Prior treatment with RAF inhibitors, Wnt pathway inhibitors, cetuximab, panitumumab, and/or other EGFR inhibitors.
• Symptomatic brain metastasis. See protocol page 38 for details.
• Use of strong inhibitors or inducers of CYP3A4/5 or herbal medications. See protocol page 38 for details.
• Acute and chronic pancreatitis, clinically significant cardiac disease. See protocol page 38 for details.
•History of thromboembolic or cerebrovascular events within the last 6 months.
• Radiation therapy that includes >30% of the bone marrow reserve, chemotherapy, biological therapy (e.g., antibodies) within <= 4 weeks (6 weeks for nitrosourea, mitomycin-C), or who have been treated with continuous or intermittent small molecule therapeutics or investigational agents within 5 half-lives of the agent.
• Pregnancy, lactation, inadequate contraception (males and females). See protocol page 39 for details.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Phase 1b: DLTs.<br /><br>Phase II: overall response rate (ORR).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Phase 1b: ORR.<br /><br>Both phases: overall survival, time to and duration of response, progression<br /><br>free survival, disease control rate, adverse effects, frequency of dose<br /><br>modifications, </p><br>