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

• Conditions: Patients With Advanced Renal Cell Carcinoma Who Have Failed First-Line Sunitinib Therapy; MedDRA version: 14.1Level: PTClassification code 10050513Term: Metastatic renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2007-000062-20-AT
• Lead Sponsor: Wyeth Pharmaceuticals Inc, a wholly owned subsidiary of Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426 USA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-03
• Last Update Posted: 15 July 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 501

Inclusion Criteria

1. Male or female subjects = 18 years.
2. Histologically confirmed diagnosis of mRCC (regardless of histologic or 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 at least 1 cycle of sunitinib therapy (minimum of 4 weeks of continuous sunitinib therapy regardless of dose).
3. At time of randomization there must be at least 2 weeks since prior treatment with sunitinib, palliative radiation therapy, and/or surgery.
4. At the time of randomization there must be at least 1 measurable lesion per RECIST criteria. Lesions that have been previously irradiated or embolized cannot be selected as target lesions. Irradiated and embolized lesions can be monitored to assess progression as non-target lesions.
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) within two weeks of randomization
Serum creatinine less than or equal to 2.0 x ULN
Total bilirubin less than or equal to 1.5 x ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN (less than or equal to 5 x ULN if liver metastases are present)
Glycosylated hemoglobin A1c (HbA1c) = 9% (hyperglycemia therapy permitted)
Prothrombin time (PT) or international normalized ratio (INR), or prothrombin activity and partial thromboplastin time (PTT) = 1.5 x ULN (Anticoagulation is allowed if the subject is on a stable dose of coumarin type anticoagulant or LMW heparin prior to randomization.)
6. Adequate cardiac function (left ventricular ejection fraction = 40%) as assessed by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan as judged by the investigator.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
8. Ability to swallow whole sorafenib tablets.
9. Life expectancy of at least 12 weeks.
10. Signed and dated institutional review board (IRB) or independent ethics committee (IEC) approved informed consent form (ICF) before any protocol specific screening procedures.
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 345
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 156

Exclusion Criteria

1. Metastatic CNS from RCC.
2. Subjects who discontinued therapy due specifically to intolerance.
3. Bone only lesions as target lesions.
4. Any prior systemic therapy for RCC/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 one week prior to randomization.
6. Not recovered from prior biopsy, surgery, traumatic injury, radiation therapy and/or has a non-healing wound or ulcer, as judged by the investigator.
7. Grade = 3 hemorrhage and/or treatment with transfusions within 2 weeks of randomization.
8. Inadequately controlled hypertension (defined as a blood pressure of > 150 mm Hg systolic and/or > 100 mm Hg diastolic on treatment.
9. Unstable coronary artery disease, as judged by the investigator, or recent myocardial infarction (< 180 days).
10. American Heart Association class 3/4 heart disease.
11. ECG QTc interval findings > 450 msec for men and > 470 msec for women and/or any uncontrolled clinically significant cardiac arrhythmia.
12. Active ketonuria, secondary to poorly controlled diabetes mellitus.
13. History of pulmonary hypertension or interstitial lung disease.
14. Receiving immunosuppressive agents within 28 days prior to randomization. Replacement doses of corticosteroids and topical/inhaled steroids are permitted.
15. Immunocompromised subjects, including known seropositivity for human immunodeficiency virus (HIV), or current or chronic hepatitis B and /or hepatitis C infection (as detected by positive testing for hepatitis B surface antigen [HbsAg] or antibody to hepatitis C virus [anit HCV] with confirmatory testing). (Note:
testing is not mandatory to be eligible for the study.)
16. Active infection(s), receiving active systemic antimicrobial therapy or serious intercurrent illness.
17. 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 disease-free at least 5 years.
18. 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.
19. Refusal to use medically acceptable contraceptive methods for 3 months after the last dose of temsirolimus or sorafenib therapy.
20. Any other significant illness residual sunitinib toxicity or medically significant abnormal laboratory finding that would, in the investigator’s judgment, make the subject inappropriate for this study, or would increase the risk associated with the subject’s participation in this study.
21. Known hypersensitivity to any of the components of the test articles or documented medical condition that would prohibit adequate premedication with antihistamine.
22. Patients currently receiving and /or have received prior investigational drugs of vaccines (except sunitinib) within the past 30 days.

Study & Design

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