| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10038407 |
| E.1.2 | Term | Renal cell cancer |
| E.1.2 | System Organ Class | 100000004864 |
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| 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 |
The objective of this study is to evaluate the antitumor activity and safety of BAY 73-4506 in previously untreated patients with metastatic or unresectable renal cell cancer (RCC).
The primary efficacy endpoint of this study is listed in section 4.6.1. |
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| E.2.2 | Secondary objectives of the trial |
| Secondary objectives include the evaluation of pharmacokinetic and biomarker data. The secondary endpoints of this trial are listed in sections 4.6.1 and 4.6.2. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•Male or female patients > 18 years of age.
•Patients, who suffer from unresectable and/or metastatic, measurable predominantly clear cell RCC histologically or cytologically documented. Patients with rare subtypes of RCC such as pure papillary cell tumor, mixed tumor containing predominantly sarcomatoid cells, Bellini carcinoma, medullary carcinoma, or chromophobe oncocytic tumors are excluded from study participation.
•Patients must be previously untreated for advanced disease. Prior palliative radiation therapy is allowed if the target lesion(s) are not included within the radiation field and no more than 30% of the bone marrow is irradiated.
•Patients who have at least one uni-dimensional measurable lesion by CT-scan or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST).
•Patients with “Intermediate” or “Low” risk per the Motzer score.
•Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1.
•Adequate bone marrow, renal and hepatic function as assessed by the following laboratory requirements to be conducted within 7 days prior to study drug treatment:
Total bilirubin < 1.5 x the upper limit of normal.
ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer).
Amylase and lipase < 1.5 x the upper limit of normal
Serum creatinine < 2.0 x the upper limit of normal.
INR/PTT < 1.5 x ULN (Patients who are being prophylactically anti-coagulated with an agent such as coumadin or low molecular weight heparin or therapeutically anticoagulated with LMWH will be allowed to participate provided that they meet these criteria; in addition, these patients must be monitored at appropriate intervals throughout study)
Platelet count ¬> 100000 /mm3, Hb > 9 g/dl, ANC > 1500/mm3
Alkaline phosphatase limit < 2.5 x ULN
•Life expectancy of at least 12 weeks.
•A signed informed consent must be obtained prior to any study specific procedures.
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| E.4 | Principal exclusion criteria |
•Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
•Patients who have received prior systemic treatment regimens for RCC. Prior systemic therapy is defined as the following: a single chemotherapy agent (or regimen), a single immunotherapy agent (or regimen) or a single investigational treatment agent (or regimen), any anti-VEGF therapy (including bevacizumab, sunitinib and sorafenib) or any mTOR inhibitor therapy (including temsirolimus). Megestrol acetate or medroxyprogesterone, used as a single agent for the first line treatment of RCC will not constitute one prior systemic therapy.
•Cardiac arrhythmias requiring anti-arrythmics (excluding beta blockers or digoxin), symptomatic coronary artery disease
•History of cardiac disease or congestive heart failure >NYHA class 2. Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
•Uncontrolled hypertension defined as systolic blood pressure 150 mmHg or diastolic pressure 90 mmHg, despite optimal medical management.
•Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
•Active clinically serious infections (> grade 2 NCI-CTC version 3.0).
•History of HIV infection or chronic hepatitis B or C.
•Known history or symptomatic metastatic brain or meningeal tumours (head CT or MRI at screening to confirm the absence of CNS disease if patient has symptoms suggestive or consistent with CNS disease).
•Patients with seizure disorder requiring medication (such as steroids or anti-epileptics).
•History of organ allograft.
•Patients with evidence or history of bleeding diasthesis. Any hemorrhage or bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study.
•Serious, non-healing wound, ulcer, or bone fracture.
•Patients undergoing renal dialysis.
•Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results.
•Known or suspected allergy to the investigational agent or any agent given in association with this trial.
•Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study.
•Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and for at least 3 months after completion of study drug. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
•Investigational drug therapy outside of this trial during or within 4 weeks of study entry
•Prior exposure to the study drug.
•Radiotherapy during study or within 3 weeks of start of study drug. Palliative radiotherapy will be allowed as described in the Prior and Concomitant Therapy section.
•Major surgery open biopsy or significant traumatic injury within 4 weeks of start of study
•Autologous bone marrow transplant or stem cell rescue within 4 months of study
•Patients unable to swallow oral medications
•Any malabsorption condition
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint of this study is to evaluate the response rate of patients with advanced RCC to BAY 73-4506. Tumor response and disease progression will be evaluated based on RECIST tumor response criteria. Measurements will be made at baseline and then every 2 cycles (8 weeks- based on 28 day cycles) during the treatment period until progressive disease is documented, and also at the end of treatment visit if applicable.
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Measurements will be made at baseline and then every 2 cycles (8 weeks- based on 28 day cycles) during the treatment period until progressive disease is documented, and also at the end of treatment visit if applicable.
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| E.5.2 | Secondary end point(s) |
| Secondary efficacy endpoints include overall survival, progression-free survival, time to progression, duration of response and duration of stable disease. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the treatment period, the same lesions to those identified and measured at baseline must be evaluated using the same technique, the identical contrast agent and the same slice thickness. The body areas scanned at baseline should also continue to be scanned throughout the study. The exception to this is a baseline negative head CT/MRI if it was performed to rule out metastatic brain or meningeal tumours.
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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 | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Biomarker studies (optional) |
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| 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 | No |
| 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.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 | No |
| 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 |
| Finland |
| France |
| Germany |
| Poland |
| United Kingdom |
| United States |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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