A Phase II, Multi-centre, Open-label Study to Assess the Efficacy, Safety, Tolerability and Pharmacokinetics of Intrapatient Dose Escalation of Sorafenib as First Line Treatment for Metastatic Renal Cell Carcinoma - ND

• Conditions: Renal cell carcinoma; MedDRA version: 9.1Level: LLTClassification code 10050513Term: Metastatic renal cell carcinoma

• Registration Number: EUCTR2007-004875-21-IT
• Lead Sponsor: BAYER

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-02-07
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

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 Total bilirubin < 1.5 times the upper limit of normal ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for subjects with liver involvement of their cancer) Alkaline phosphatase < 2.5 x ULN PT-INR/PTT < 1.5 x upper limit of normal. Subjects who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists. For subjects on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre dose, as defined by the local standard of care (exluding subjects being anticaogulated for deep vein thrombosis and/or pulmonary embolus occurring within 12 months of the start of treatment). Serum creatinine < 1.5 x upper limit of normal Signed informed consent must be obtained prior to any study specific procedures. Subjects must have received no prior systemic anticancer therapy for the treatment of their renal cell carcinoma Prior nephrectomy Prior palliative radiotherapy to metastatic lesion(s) is permitted
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 arrythmias requiring anti-arrythmic 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-CTC 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 (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies) Any ongoing requirement for systemic corticosteroid therapy Subjects with seizure disorder requiring medication (such as steroids or anti-epileptics) History of organ allograft Subjects with evidence or history of bleeding diasthesis Deep vein thrombosis/ pulmonary embolus within 12 months of the start of treatment or ongoing need for full-dose oral or parenteral anticoagulation Delayed healing of wounds, ulcers or bone fractures Pre-existing thyroid abnormality 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 two weeks 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. Any prior systemic anticancer therapy including cytotoxic therapy, targeted agents, experimental therapy, adjuvant, or neo-adjuvant therapy. 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 weeks 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 Use of St. John?s Wort, rifampin (rifampicin), or other drug metabolizing enzyme inducers and herbal medications within 2 weeks prior to first dose of study drug. Use of these

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: Safety and tolerability Pharmacokinetics Progression free survival (PFS) Time to progression (TTP);Primary end point(s): The primary endpoint is to assess the response rates observed in patients treated with a continuous, daily dose of sorafenib escalated from 400mg to a maximum of 800mg bid.;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 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.