Colorectal cancer MedDRA version: 21.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tagrisso
Pharmaceutical Form: Tablet
Sponsors
Radboud University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Group 1 • Diagnosed with PM of CRC • Candidate for CRS-HIPEC according to the multidisciplinary gastrointestinal tumor board • 18 years or older • WHO performance status 0 or 1 • Adequate haematologic and organ function defined as: o ALAT and AST = 5x upper limit of normal (ULN) o Alkaline phosphatase = 5x ULN o Total bilirubin = 1.5x ULN; = 3x ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinaemia) or liver metastasis o Haemoglobin = 5.6 mmol/L o Absolute Neutrophil count (ANC) = 1.5 x 10*9/L o Platelet count = 100 x 10*9/L • Written informed consent • Able to swallow oral medication Group 2 • Diagnosed with liver metastasis of CRC • Candidate for primary resection of at least one liver metastasis according to the multidisciplinary gastrointestinal tumor board • 18 years or older • WHO performance status 0 or 1 • Adequate haematologic and organ function defined as: o ALAT and AST = 5x upper limit of normal o Alkaline phosphatase = 5x ULN o Total bilirubin = 3x ULN o Haemoglobin = 5.6 mmol/L o Absolute Neutrophil count (ANC) = 1.5 x 10*9/L o Platelet count = 100 x 10*9/L • Written informed consent • Able to swallow oral medication 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 8 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: • Not fit to undergo surgery • Concurrent participation in another clinical trial using any medicinal product • The use of concomitant drugs that interact with osimertinib according to the Summary of Product Characteristics (SPC) including: o Strong and moderate CYP3A4 inducers o St. John’s Wort o Substrates of breast cancer resistant protein (BCRP) and P-glycoprotein (P-gp) substrates, including rosuvastatin, fexofenadine, digoxin, dabigatran and aliskiren. • An active contraindication for the use of osimertinib or a situation in which use of osimertinib is not recommended according to the SPC • Mean resting corrected QT interval (QTc) > 470 msec at screening • Medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that requires steroid treatment, or any evidence of clinically active ILD • Inability to comply with protocol or study procedures • Women who are pregnant, plan to become pregnant or are lactating during the study or for up to 3 months after the last dose of the study drug • Substance abuse, medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results • Minors or incapacitated subjects • Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the intratumoral concentration of osimertinib in peritoneal metastasis upon 2 weeks of treatment of patients who are candidate for CRS-HIPEC treatment (group 1), and in liver metastasis of patients who are candidate for primary liver resection (group 2). These clinical determined intratumoral osimertinib concentrations will be compared with the effective tissue concentrations in PDTOs from PM of CRC from the PDO-CRPM study.;Secondary Objective: •To assess inter- and intrapatient variability in intratumoral osimertinib concentrations •To measure osimertinib concentration in ascites (if present at surgery) and plasma •Correlation between plasma, ascites, healthy tissue and intratumoral concentration •To determine differences in intratumoral TKI concentrations between PM and liver metastasis •To assess the safety and tolerability of pre-operative osimertinib treatment for 2 weeks in patients who will undergo CRS-HIPEC for PM of CRC (group 1) and in patients who will undergo primary liver resection or liver metastasis of CRC (group 2) ;Primary end point(s): Intratumoral osimertinib concentration in peritoneal metastasis and liver metastasis.;Timepoint(s) of evaluation of this end point: At the end of the study period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Intra- and interpatient variability in intratumoral osimertinib concentrations. Relation between osimertinib concentration in ascites, plasma and healthy tissue vs intratumoral osimertinib concentration. Safety and tolerability of pre-operative osimertinib treatment. ;Timepoint(s) of evaluation of this end point: At the end of the study period. | — |
Countries
Netherlands
Contacts
Public ContactNielka van Erp
Radboud University Medical Center
Outcome results
None listed