E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic renal cell carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
metastatic (spread) kidney cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the proportion of patients that is progression-free at 3 months upon retreatment with sunitinib. |
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E.2.2 | Secondary objectives of the trial |
To assess the clinical benefit rate, median progression-free survival and overall survival in individuals retreated with sunitinib
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.
To evaluate the effect of retreatment with sunitinib on the quality of life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To investigate the proportion of patients that is progression-free at 3 months upon retreatment with sunitinib. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To assess the clinical benefit rate, median progression-free survival and overall survival in individuals retreated with sunitinib
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.
To evaluate the effect of retreatment with sunitinib on the quality of life |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |