renal cell carcinoma MedDRA version: 9.1 Level: LLT Classification code 10050513 Term: Metastatic renal cell carcinoma
Conditions
Sponsors
Bayer Healthcare AG, D-51368 Leverkusen, Germany
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age > 18 years. • Histological or cytological documentation of metastatic and/or unresectable clear cell RCC is required • Subjects with at least one uni-dimensional measurable lesion. Lesions must be measured by CT-scan or MRI according to Response Evaluation Criteria in Solid Tumours (RECIST). • ECOG Performance Status of 0 or 1 • MSKCC good or intermediate category • Life expectancy of at least 12 weeks. • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: • Hemoglobin > 9.0 g/dl • Absolute neutrophil count (ANC) >1,500/mm3 • Platelet count ? 100,000/?l • Total bilirubin =65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • History of cardiac disease; • congestive heart failure >NYHA class 2 • active CAD (MI more than 6 mo prior to study entry is allowed) • cardiac arrhythmias requiring anti-arrhythmic therapy( beta blockers or digoxin are permitted) • uncontrolled hypertension (defined as blood pressure >160mmHg systolic and/or > 90mmHg diastolic on medication) • History of HIV infection or chronic hepatitis B or C • Active clinically serious infections (> grade 2 NCI-CTCAE version 3.0) • Symptomatic metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also the subject must not be undergoing acute steroid therapy or taper therapy (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies) • Subjects with seizure disorder requiring medication (such as steroids or anti-epileptics) • History of organ allograft • Subjects with evidence or history of bleeding diathesis • Deep vein thrombosis and/or pulmonary embolus within 12 months of the start of treatment. • Delayed healing of wounds, ulcers or bone fractures • Subjects with pre-existing thyroid abnormality whose thyroid function cannot be maintained within the normal range by medication • Subjects undergoing renal dialysis • 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. • Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study • Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to 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 three months after the completion of trial. The investigator is requested to advise the subject how to achieve an adequate contraception. • Subjects unable to swallow oral medications. This applies to subjects with severe obstruction of upper GI that require gavage. Excluded therapies and medications, previous and concomitant: • Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy (adjuvant or neo-adjuvant therapy including IFN-IL2-5FU is permitted). • Prior adjuvant sorafenib is excluded. • Radiotherapy during study or within 3 weeks of start of study drug • Major surgery within 4 weeks of start of study • Autologous bone marrow transplant or stem cell rescue within 4 months of study • Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction.] Subjects taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study. • Investigational drug therapy outside of this trial during or within 4 weeks of study entry • Subst
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of intrapatient dose escalation in previously untreated subjects with mRCC. The initial dose of sorafenib will be 400mg bid administered orally, on a continuous basis. Intrapatient dose escalation will occur as defined in the table below, providing no grade 3 or 4 toxicities (except for alopecia, nausea and vomiting) are observed. The primary objective is to assess the response rates (by independent assessment) observed in subjects treated with a continuous, daily dose of 400 mg bid sorafenib dose escalated up to 800mg bid. ;Secondary Objective: The secondary objectives are to assess the following: • Safety and tolerability • Pharmacokinetics • Progression free survival (PFS) • Time to progression (TTP) ;Primary end point(s): Primary end point is to assess the response rates observed for patients treated with continuous daily dose of sorafenib escalated from 400mg to 600mg to a maximum of 800mg bid. | — |
Countries
France, Germany, Italy, United Kingdom
Outcome results
None listed