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A Phase Ib, multicenter, open-label dose escalation and expansion platform study of select druk combinations in adult patients with advanced or metastatic BRAF V600 colorectal cancer.

Completed
Conditions
advanced or metastatic BRAF V600
10017991
Registration Number
NL-OMON52799
Lead Sponsor
ovartis
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
21
Inclusion Criteria

Patients must be >= 18 years of age.
ECOG performance status <= 1.
Patients must have a site of disease amenable to biopsy, and be a candidate for
tumor biopsy according to the treating institution*s guidelines.
All patients must have a BRAF V600 mutation confirmed by local assessment.
Patients with unresectable advanced/metastatic BRAF V600 cancer of the colon or
rectum with measurable disease as determined by RECIST v1.1
See for more details protocol section 5.1

Exclusion Criteria

Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of study drugs
Patients with CNS tumor involvement, unless > 2 weeks after completion of
CNS-therapy, stable with respect to CNS-involvement, not receiving steroids or
on stable dose of < 10 mg/day for two weeks.
Out of range laboratory values:
Hemoglobin (Hgb) < 9.0 g/dL
Platelets < 75 x 109/L
Serum total bilirubin > 1.5 x upper limit of normal (ULN),
Asparate aminotransferase (AST) > 3 x ULN
Alanine aminotransferase (ALT) > 3 x ULN
Serum creatinine > 1.5 x ULN OR Creatinine Clearance < 60 mL/min
Other exclusion criteria may apply, please see protocol section 5.2

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>Incidence and severity of AEs and SAEs, including changes in laboratory values,<br /><br>vital signs, and ECGs<br /><br>Incidence and nature of DLTs in the first cycle (dose escalation only)<br /><br>Dose interruptions, reductions, and dose intensity</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>Tumor MAPK pathway suppression (change from baseline) within combination<br /><br>treatment arms<br /><br>Tumor mutational changes throughout treatment course<br /><br>Tumor immune phenotyping within combination treatment arms (e.g. CD8, PD-L1)<br /><br>BOR per RECIST v1.1<br /><br>For individual investigational drug, compare the PK in combination regimen vs.<br /><br>as a single agent</p><br>
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