E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically confirmed renal cell carcinoma with metastases with a component of clear (conventional) cell histology |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7,1 |
E.1.2 | Classification code | 10038415 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To evaluate the activity of SU011248 in cytokine-refractory metastatic RCC when administered in a continuous treatment regimen
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of SU011248 administered in a continuous treatment regimen - To evaluate the tolerability of SU011248 administered in the morning versus in the evening prior to sleep - To assess patient reported outcomes (PRO) - To determine SU011248 and SU012662 trough concentrations (Ctrough) for evaluation of steady-state pharmacokinetics -To explore the correlations of potential biomarkers with clinical outcomes |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Histologically proven renal cell carcinoma with metastases 2. Evidence of unidimensionally measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST). 3. Failure of 1 prior cytokine-based therapy for metastatic disease. Patients treated with IFN-alpha alone must have received IFN-alpha for at least 4 weeks. 4. Male or female, 18 years of age or older. 5. ECOG performance status 0 or 1. 6. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade : less/equal to 1. 7. Adequate organ function as defined by the following criteria:· - Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) less/equal to 2.5 x upper limit of normal (ULN), or AST and ALT less/equal 5 x ULN if liver function abnormalities are due to underlying malignancy· - Total serum bilirubin less/equal 1.5 x ULN - Absolute neutrophil count (ANC) major/equal to 1500/uL - Platelets major/equal to 100,000/uL - Hemoglobin major/equal to 8.0 g/dL without support of growth factors - Serum calcium less/equal 12.0 mg/dL - Serum creatinine less/equal 1.5 x ULN 8. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. 9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. |
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E.4 | Principal exclusion criteria |
1. Prior treatment with any systemic therapy other than 1 cytokine-based therapy. 2. Previous treatment on a SU011248 clinical trial. 3. Major surgery, radiation therapy, or systemic therapy within 4 weeks of starting the study treatment. 4. Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma that has been adequately treated with no evidence of recurrent disease for 12 months. 5. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease on screening CT or MRI scan. 6. Any of the following within the 12 months prior to starting the study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism. 7. Ongoing cardiac dysrhythmias of grade major/equal to 2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females. 8. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). 9. Ongoing treatment with therapeutic doses of Coumadin (however, low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). 10. Known human immunodeficiency virus (HIV) infection. 11. Current treatment on another therapeutic clinical trial. 12. Pregnancy or breastfeeding. Patients must be surgically sterile, be postmenopausal, or must agree to use effective contraception during the period of therapy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to study treatment. 13. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into the trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective Response Rate (ORR) |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | Yes |
E.7.1.3.1 | Other trial type description |
therapeutic exploratory, Phase II |
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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 | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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Treatment will continue up to one year until disease progression, significant toxicty, withdrawal of consent. Withdrawal takes place in case of disease progression (without clinical benefit), unacceptable toxicity, need for treatment rest >4 weeks, need to reduce dose to <25 mg/day, need for anticancer therapy not specified in protocol, congestive heart failure, noncompliance, lost to follow-up, choice to withdraw from treatment / from study, completion of 1 year of treatment. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |