Metastatic colorecal adenocarcinoma, K-RAS and N-RAS wild type.
Conditions
Interventions
89Zr-cetuximab PET scan: After a therapeutic dose of cetuximab, 10mg of 89Zr-cetuximab is injected. Six days after injection a PET-scan will be made. If this scan is considerd positive, meaning uptake
Sponsors
VU University Medical Center (central site)
UMC Groningen
Radboud UMC
Eligibility
Inclusion criteria
Inclusion criteria: • Advanced colorectal adenocarcinoma • Subjects must have been treated according to standard care with palliative chemotherapy including a fluoropyrimidine (e.g. fluorouracil or capecitabine), irinotecan, and oxaliplatin or had contra-indications to treatment with these drugs. • No local treatment options • Life expectancy of at least 12 weeks. • Age >= 18 years. • Histological or cytological documentation of cancer is required. • Tumor material must be tested wild type for the K-RAS (codon 12, 13, 61, 117, 146) and N-RAS (codon 12, 13, 61, 117, 146) genes. • 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). • 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 start of treatment: 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.
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 |
|---|---|
| 89Zr-cetuximab uptake in non-hepatic metastases (corrected VOIs) and the correlation with clinical benefit rate. 89Zr-cetuximab uptake in non-hepatic metastases with increased dosing of cetuximab (corrected VOIs). The clinical benefit rate (CR, PR and SD) based upon 89Zr-cetuximab image adjusted dosing | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. Tumor perfusion measured with 15O-H2O-PET before and after 2 weeks of cetuximab treatment. 4. Grade of skin toxicity as measured by predefined criteria. 5. Serum magnesium levels before and during treatment. 6. EGFR expression and saturation with cetuximab in tumor and skin biopsies. 7. (Phospho)proteomic and peptide profiles in tumor, blood and skin biopsies before and during treatment with cetuximab. 8. Mutation analysis of K-RAS, N-RAS, B-RAF and other genes potentially involved in response to therapy before, during therapy with cetuximab and at progression in circulating tumor DNA. 9. Mutation analysis of B-RAF and other genes potentially involved in response to therapy before and during therapy with cetuximab in tumor biopsies. 10. PFS and OS in the standard treatment group, in the dose escalation group and in the dose extension group. 11. miRNA in blood and tumor biopsies before and during treatment with cetuximab 12. Effects of skin toxicity due to (escalating doses of) cetuximab monotherapy on health related QoL. 13. Utility and health technology assessment of the intervention and the gain of quality-adjusted life years (QALY). | — |
Contacts
Public ContactE. Helden, van
VU University Medical Center De Boelelaan 1117 Room ZKH 3A18
Outcome results
None listed