A Randomized Trial of Temsirolimus and Sorafenib as Second-Line Therapy in Patients with Advanced Renal Cell Carcinoma Who Have Failed First-Line Sunitinib Therapy - ND

• Conditions: Patients With Advanced Renal Cell Carcinoma Who Have Failed First-Line Sunitinib Therapy; MedDRA version: 9.1Level: LLTClassification code 10050513Term: Metastatic renal cell carcinoma

• Registration Number: EUCTR2007-000062-20-IT
• Lead Sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc Global Medical Affairs

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-06-18
• Last Update Posted: 15 July 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 440

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 1.
3.At least 1 measurable lesion that can be accurately measured in at least 1 dimension with the longest diameter (LD)  10 mm when measured by spiral computerized tomography (CT) (5-mm slice thickness contiguous) or  20 mm when measured by conventional CT (10-mm slice thickness contiguous). The lesion must be  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  1.5 x 109/L (1500/mL)
Platelet count  100 x 109/L (100,000/mL)
Leukocyte count  3 x 109/L (3000/μL)
Hemoglobin  80g/L (8.0g/dL) without transfusion within 28 days before randomization
Serum creatinine  2.0 x upper limit of normal (UNL)
Total bilirubin  1.5 x ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)  3 x ULN (5  ULN if liver metastases are present)
Fasting serum cholesterol 2.0 x ULN (therapy permitted)
Fasting serum triglycerides  2.0 x ULN (therapy permitted)
Fasting glycosolated hemoglobin A1c (HbA1c) ≤ 9% (therapy permitted)
Corrected serum calcium  1.5 x ULN (corrected calcium = total calcium ? 0.707 [albumin ? 3.4 g/dL]. If a laboratory reports total calcium in mmol/L, results should be converted to mg/dL using 0.249 as conversion factor
Partial thromboplastin time within normal limits (WNL)and international normalized ratio or prothrombin time or prothrombin activity < 1.3 x ULN
Amylase and lipase  1.5 x ULN
Sensitive thyroid stimulating hormone (sTSH)  5 x ULN
Serum magnesium  0.41 mmol/L (1.0 mg/dL) (therapy permitted)
Serum phosphorus  0.78 mmol/L (2.5 mg/dL) (therapy permitted)
Serum uric acid  588 mcmol/L (10 mg/dL) (therapy permitted)
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6.Adequate cardiac function (left ventricular ejection fraction ≥ 40%) as assessed by electrocardiogram (ECG), and either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan as judged by the investigator and the sponsor?s medical monitor if abnormal.
7.Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
8.Ability to swallow whole sorafenib tablets.
9.Life expectancy of at least 3 months.
10. Signed and dated institutional review board (IRB) or independent ethics committee (IEC) approved informed consent form (ICF).
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

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  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 (< 180 days).
11.American Heart Association class 3/4 heart disease.
12.QTc interval > 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 p

Study & Design

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