Phase II study of sunitinib rechallenge in patients with metastatic renal cell carcinoma.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 45

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

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), evidence of or symptoms compatible with cardiac failure class III or IV according to the New York Heart Association Functional Classification.
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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To investigate the proportion of patients that is progression-free at 3 months<br /><br>upon retreatment with sunitinib. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>(1) To assess the clinical benefit rate, median progression-free survival and<br /><br>overall survival in individuals retreated with sunitinib. (2) To assess the<br /><br>effects of sunitinib rechallenge on (a) expression of LAMP1/2 proteins in<br /><br>circulating mononuclear cells and in tumor tissue (b) the number and activation<br /><br>state of circulating DC, MDSC and Tregs (c) sunitinib drug levels (d) sunitinib<br /><br>tumor tissue concentrations (e) intratumoral phosphoproteomic profiles. (3) To<br /><br>evaluate the effect of retreatment with sunitinib on the quality of life.</p><br>

Related Trials

Retreatment with sunitinib in patients with metastatic (spread) kidney cancer.

Phase 1

VU University Medical Center

Updated 2/28/2019