Metastatic renal cell cancer - uitgezaaide nierkanker Sunitinib rechallenge - herbehandeling met sunitinib Sunitinib - Sunitinib
Conditions
Interventions
Patients will be treated in repeated 6-week cycles with 50 mg sunitinib orally daily for 4 weeks followed by 2 weeks off.
Sponsors
VU Medical Center
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients with histologically or cytologically confirmed clear-cell mRCC; 2. Patients who progressed on first-line treatment with sunitinib and who had clinical benefit defined as a response (according to RECIST 1.1 criteria) or SD for more than 6 months on this treatment; 3. Patients who progressed after second-line treatment (mTOR inhibitor or other treatment as long as patients are not treated with a VEGF targeted TKI, see exclusion criteria), or who progressed after a treatment-free interval of at least 3 months since discontinuation of first-line sunitinib treatment; 4. Patients with radiological (and/or clinical) confirmed progressive disease according to RECIST 1.1 criteria; 5. Measurable or evaluable disease as defined by RECIST 1.1; 6. WHO performance status 0-2; 7. Life expectancy of at least 12 weeks; 8. Age 18 years or older; 9. Able to receive oral medication; 10. Able to provide written informed consent; 11. Adequate hematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, Hb ≥ 6.0 mmol/L; 12. Patients with brain metastases are eligible if they have been stable for at least two months post-radiation therapy or surgery; 13. No other current malignant disease, except for basal cell carcinoma of the skin; 14. Adequate hepatic function: serum bilirubin ≤ 1.5 x ULN, ALT and AST ≤ 2.5 x ULN (or ≤ 5 times ULN if liver metastases are present); 15. Renal function: estimated glomerular filtration rate ≥ 40 ml/min; 16. Patients with reproductive potential must use effective contraception. Female patients must have a negative pregnancy test.
Exclusion criteria
Exclusion criteria: 1. Patients treated with any VEGF targeted TKI (sorafenib, pazopanib, axitinib, dovitinib) as second-line treatment after progression on first-line sunitinib treatment; 2. Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 2 separate measurements on at least 2 separate days; 3. Active infection or serious intercurrent illness; 4. Presence of unstable angina, recent myocardial infarction (within the previous 3 months); 5. Macroscopic hematuria; 6. Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient’s compliance; 7. Any other major illness that, in the investigator’s judgment, substantially increases the risk associated with the subject’s participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To investigate the proportion of patients with mRCC retreated with sunitinib that is progression-free at 3 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To assess the clinical benefit rate (ORR and SD), mPFS and OS in individuals retreated with sunitinib; 2. To assess the effects of sunitinib rechallenge on LAMP1/2 proteins in PBMCs and tumor tissue; 3. To assess the immunological effects of sunitinib rechallenge on the number and activation state of circulating DC, MDSC and Tregs; 4. To study phosphoproteomic profiles of tumors before rechallenge and at the time of progression; 5. To assess sunitinib drug levels and tumor tissue concentrations of sunitinib; 6. To evaluate the effect of retreatment with sunitinib on the quality of life. | — |
Contacts
Public ContactH.M.W. Verheul
De Boelelaan 1117
Outcome results
None listed