metastatic colorectal cancer MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Erbitux
Product Name: cetuximab
Product Code: L01XC06
Pharmaceutical Form: Solution for infusion
Product Name: cetuximab-N-SUCDF-89ZR
Product Code: 89ZR-cetuximab
Pharmaceutical Form: Sol
Sponsors
VU University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Advanced colorectal adenocarcinoma • Subjects must have been treated according to standard care with a fluoropyrimidine (e.g. fluorouracil or capecitabine), irinotecan, and oxaliplatin or had contra-indications to treatment with these drugs. • Age = 18 years. • Histological or cytological documentation of cancer is required. • Tumor material must be tested wild type for the K-RAS and B-RAF gene. • Tumor lesion: o Part I: Subjects have at least one measurable lesion = 2 cm outside the liver. Lesions must be evaluable by CT or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). o Part II: Subjects have at least one measurable tumor lesion = 1 cm, including liver tumor lesion. Lesions must be evaluable by CT or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). • ECOG Performance Status of 0, 1 or 2 • Adequate liver and renal functions as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: o Total bilirubin = 1.5 times the upper limit of normal o ALT and AST = 2.5 times upper limit of normal (= 5 times upper limit of normal for subjects with liver involvement of their cancer) o Serum creatinin = 1.5 times upper limit of normal or a calculated creatinin clearance = 50 ml/min • Signed informed consent must be obtained prior to any study specific procedures. 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 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 76
Exclusion criteria
Exclusion criteria: • Previous exposure to an anti-EGFR therapy • Significant skin condition interfering with treatment • Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must agree to use adequate barrier birth control measures (e.g., cervical cap, condom, and diaphragm) during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between study drug and oral contraceptives. Concomitant use of oral and barrier contraceptives is advised. Contraception is necessary for at least 6 months after receiving study drug. • Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy during the study or within 4 weeks of the start of study drug. • Radiotherapy to the target lesions during study or within 4 weeks of the start of study drug. Palliative radiotherapy will be allowed. • Major surgery within 28 days of start of 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. • 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 |
|---|---|
| Timepoint(s) of evaluation of this end point: 4 - 6 years after study commences;Main Objective: PART I: 1) to demonstrate 89Zr-cetuximab uptake in non-hepatic tumor lesions at standard dose or at cohort wise increased cetuximab doses (dose escalation). 2) to determine the association between 89Zr-cetuximab uptake in non-hepatic tumor lesions and treatment response. 3) to determine the association between metabolic change (evaluated with 18F-FDG PET after 2 weeks of treatment) and treatment response. PART II 1)Validate early response evaluation with 18F-FDG PET and the association with treatment benefit. 2) Evaluate optimal quantification methods for 18F-FDG PET images ;Secondary Objective: - association between levels of uptake of 89Zr-cetuximab in the liver vs. levels of uptake in non-hepatic tumor lesions -pharmacokinetics of 89Zr-cetuximab and cetuximab -Can the response observed on [18F]-FDG-PET serve as an early response marker for future response to targeted therapy according to RECIST1.1? -Explore tumor perfusion with 15O-H2O in a subgroup of patients. These data will serve to explain whether and how 89Zr-cetuximab uptake is a function of tumor perfusion. -association between 89Zr-cetuximab uptake in tumor lesions, grade of skin toxicity, serum magnesium concentration abnormalities and response according to RECIST1.1? -Relation of tumor and serum microRNA (miRNA) profiles and response to therapy? -Study tumor (phospho)proteomic and serum peptide profiles in relation to response to therapy. -Study germline and tumor DNA mutation profiles in relation to response to therapy. -Study circulating tumors cells (CTCs) in relation to response to therapy.;Primary end point(s): Part 1A: 89Zr-cetuximab uptake in non-hepatic metastases (corrected VOIs); Clinical benefit rate (CBR). Part 1B: 89Zr-cetuximab uptake in non-hepatic metastases with increased dosing of cetuximab (corrected VOIs). Part 2: Association between CBR and early response evaluation using 18F- | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) The % uptake (of total injected) 89Zr-cetuximab in non-tumor liver tissue and hepatic metastases (corrected VOIs). 2) 18F FDG-PET uptake before and after 2 weeks of cetuximab treatment. 3) Grade of skin toxicity as measured by predefined criteria. ;Timepoint(s) of evaluation of this end point: 4 - 6 years after study commences 1 year follow-up and data analysis | — |
Countries
Netherlands
Contacts
Public ContactTrial Office
VU University Medical center
Outcome results
None listed