Patients With Advanced Renal Cell Carcinoma Who Have Failed First-Line Sunitinib Therapy
Conditions
Interventions
Product Name: TEMSIROLIMUS
Product Code: CCI-779
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: TEMSIROLIMUS
CAS Number: 162635-04-3
Current Sponsor code: CCI-779
Con
Sponsors
Wyeth Research Division of Wyeth Pharmaceuticals Inc. Global Medical Affairs
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of mRCC (regardless of nephrectomy status) with well-documented radiological progressive disease (PD) by RECIST criteria or clinical PD, as judged by the investigator while receiving first-line sunitinib therapy. Subjects must have received a minimum of 1 six-week cycle of sunitinib therapy. 2. At least 2 weeks since prior treatment with sunitinib, palliative radiation therapy, and/or surgery and resolution of all toxic effects of prior therapy according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE, version 3.0) Grade or equal to 20 mm when measured by conventional CT (10-mm slice thickness contiguous). The lesion must be > or equal to 2 times the size of the slice thickness per RECIST criteria. 4. Age = 18 years. 5. Screening laboratory values within the following limits: Absolute neutrophil count > or equal to 1.5 x 109/L (1500/mL) Platelet count > or equal to 100 x 109/L (100,000/mL) Leukocyte count > or equal to 3 x 109/L (3000/µL) Hemoglobin > or equal to 80g/L (8.0g/dL) without transfusion within 28 days before randomization Serum creatinine or equal to 0.41 mmol/L (1.0 mg/dL) (therapy permitted) Serum phosphorus > or equal to 0.78 mmol/L (2.5 mg/dL) (therapy permitted) Serum uric acid =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of a central nervous system (CNS) malignancy or metastatic disease to the CNS and subjects with a known, active CNS malignancy (primary or metastatic). 2. Subjects who do not have clear evidence of PD while receiving at least 1 six-week cycle of sunitinib therapy, but who discontinued therapy due to intolerance. 3. Bone only/non-measurable bone lesions as target lesions. 4. Any prior systemic therapy for mRCC other than sunitinib. 5. Receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers. Subjects taking CYP3A4 isoenzyme inhibitors and/or inducers not classified as strong are eligible, provided the subject has been on a stable regimen for at least 4 weeks before screening. 6. Not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy, as judged by the investigator. 7. Nonhealing wound or ulcer. 8. Grade > or equal to 3 hemorrhage within the past month. 9. Systolic blood pressure of > 160 mm Hg and/or diastolic pressure > 100 mm Hg (antihypertensive medications are permitted). 10. Unstable coronary artery disease, as judged by the investigator, or recent myocardial infarction ( 450 ms for men and > 470 ms for women and/or any ventricular arrhythmia and/or any uncontrolled atrial arrhythmia. 13. Receiving anticoagulation with warfarin (low dose warfarin for catheter patency is permitted). Low molecular weight (LMW) heparin is permitted. 14. HbA1c > 9% despite therapy. 15. Active ketonuria, urinary tract infection, or gross hematuria Urinalysis with > 2+ proteinuria (approximately equivalent to 1 g/L or 100 mg/dL), any ketones, any leukocyte esterase, any nitrites, gross hematuria, or > 1+ glucosuria (approximately equivalent to 1.46 mmol/L or 250 mg/dL) 16. Untreated, symptomatic hypothyroidism. 17. History of pulmonary hypertension or interstitial lung disease. 18. Receiving immunosuppressive agents within 4 weeks of the screening visit. Replacement doses of corticosteroids and topical/inhaled steroids are permitted. 19. Chronic viral/bacterial/fungal illnesses such as human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection. Subjects may be included if they are hepatitis B and/or hepatitis C antibody positive as long as they are hepatitis surface antigen negative and/or hepatitis C RNA negative, respectively. 20. Active infection(s), receiving active systemic antimicrobial therapy or serious intercurrent illness. 21. A “currently active” second malignancy other than non-melanoma skin cancers. Subjects are not considered to have a “currently active” malignancy if they have completed anticancer therapy and are considered by their physician to be at less than 30% risk of relapse. 22. Pregnant or nursing women, women who are of childbearing potential (biologically capable of becoming pregnant) who are not using a medically acceptable contraceptive method, or men who are not using a medically acceptable contraceptive method with partners of childbearing potential. 23. Refusal to use medically acceptable contraceptive methods for 3 months after the last dose of temsirolimus or sorafenib therapy. 24. Any other major illness that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in this study. 25. Known hypersensitivity to any of the components in the temsirolimus infusion or sorafenib product or other medica
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -·To compare the safety and tolerability of temsirolimus and sorafenib when used as single agents in the second-line setting in subjects with advanced RCC who have failed prior first-line treatment with sunitinib. -·To compare the efficacy, as measured by PFS (determined by independent assessment), of temsirolimus and sorafenib when used as single agents in the second-line setting in subjects with advanced RCC who have failed prior first-line treatment with sunitinib;Secondary Objective: - To examine additional efficacy endpoints including: - PFS by investigator assessment - Response rate (CR and PR) by RECIST criteria - OS - SD at 12, 24, and 36 weeks - Duration of response - Best/maximum tumor shrinkage in target lesions;Primary end point(s): PFS by independent assessment | — |
Countries
Austria, Denmark, Finland, France, Germany, Hungary, Italy, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed