To determine whether sunitinib rechallenge in patients with mRCC, who had benefit from prior treatment with sunitinib and who progressed on both sunitinib and second-line therapy (or a period of more than 3 months without treatment), can again…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To investigate the proportion of patients that is progression-free at 3 months
upon retreatment with sunitinib.
Secondary outcome
(1) To assess the clinical benefit rate, median progression-free survival and
overall survival in individuals retreated with sunitinib. (2) To assess the
effects of sunitinib rechallenge on (a) expression of LAMP1/2 proteins in
circulating mononuclear cells and in tumor tissue (b) the number and activation
state of circulating DC, MDSC and Tregs (c) sunitinib drug levels (d) sunitinib
tumor tissue concentrations (e) intratumoral phosphoproteomic profiles. (3) To
evaluate the effect of retreatment with sunitinib on the quality of life.
Background summary
Targeted therapies are associated with (acquired) resistance after a median of
5-11 months of treatment, resulting in disease progression, while almost no
tumors are intrinsically resistant in the first line setting. We recently
published that tumor cell resistance to sunitinib may be directly related to
lysosomal sequestration of sunitinib. This resistance mechanism was shown to be
transient, since a drug-free culture period could normalize the lysosomal
storage capacity for sunitinib and resulted in recovery of drug sensitivity.
In two reports it has been suggested that patients with mRCC who responded to
sunitinib in the first-line setting may benefit from rechallenge with sunitinib
treatment after second-line treatment failure. However, these data are
retrospective. A prospective trial to investigate rechallenge with sunitinib is
needed to determine whether this strategy is of benefit for patients with mRCC
with prior clinical benefit to sunitinib but stopped treatment because of overt
clinical resistance.
Study objective
To determine whether sunitinib rechallenge in patients with mRCC, who had
benefit from prior treatment with sunitinib and who progressed on both
sunitinib and second-line therapy (or a period of more than 3 months without
treatment), can again induce a meaningful clinical benefit.
Study design
A multi-center single arm phase II study.
Intervention
Patients will be treated in repeated 6-week cycles with 50 mg sunitinib orally
daily for 4 weeks followed by 2 weeks off.
Study burden and risks
The most common adverse events due to sunitinib treatment are fatigue,
diarrhea, nausea, skin and hair discoloration, hand-foot syndrome, rash,
hypertension, fever, mucositis/stomatitis, vomiting, dyspepsia, abdominal pain,
constipation, taste alteration, headache, back pain, extremity pain, cough,
dyspnea, anorexia, and bleeding.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-002891-15-NL |
| CCMO | NL41280.029.12 |