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Study Summary
No. 2008-0322:.......Kidney......Nizar M. Tannir......Genitourinary Medical Oncology
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Study Summary Title
Study Summary
Number:
2008-0322
Study Title: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 (3066K1-404-WW)
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Physician New Patient Referral
Name:Nizar M. TannirPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Genitourinary Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2830
Contact us about clinical trials
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General Information
Disease Group:KidneySupported By:Wyeth Pharmaceuticals
Phase of Study:Phase IIReturn
Visit:
Patients assigned to temsirolimus group will be required to return weekly.
Patients assigned to sorafenib will be required to come back to the clinic
about every 2 weeks while on study.
Treatment
Agents:
Sorafenib
Temsirolimus
Home Care:Patients assigned to sorafenib group will be required to self administer oral
medication daily.
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to learn if either ToriselŽ
(temsirolimus) or NexavarŽ (sorafenib) will help to control advanced kidney
cancer in patients whose disease got worse while they were taking sunitinib
malate. The safety of these drugs will also be studied.
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Study Objectives / Outcomes
The primary objectives of this study are:
  • To compare the safety and tolerability of temsirolimus and sorafenib when used as single agents in the second-line setting in subjects with advanced renal cell carcinoma (RCC) who have failed prior first-line treatment with sunitinib due to progressive disease (PD).
  • To compare the efficacy, as measured by progression free survival (PFS) (determined by centralized 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.
The secondary objective of this study is:
  • To examine additional efficacy endpoints including:
    • PFS by investigator assessment
    • Response rate (complete response [CR] and partial response [PR] by Response Evaluation Criteria in Solid Tumors, RECIST criteria) by independent assessment
    • Overall survival (OS)
    • Proportion of subjects with PFS at 12, 24 and 36 weeks by independent assessment
    • Duration of response
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Study Status Information
Study Activation / Registration Date:09/09/2009
IRB Review and Approval Date:09/09/2009
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Terminated
Projected Accrual:480
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Male or female subjects >/= 18 years.

2) Histologically confirmed diagnosis of mRCC (regardless of histology or nephrectomy status) with well-documented radiological PD by RECIST criteria or clinical PD, as judged by the investigator, while receiving first-line sunitinib therapy. Subjects must have received at least one cycle of sunitinib therapy (minimum of 4 weeks of continuous sunitinib therapy regardless of dose).

3) At the 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: a.) Absolute neutrophil count >/= 1.5 x 10^9/L (1500/mL) b.) Platelet count >/= 100 x 10^9/L (100,000/mL) c.) Leukocyte count >/= 3 x 10^9/L (3000/microL) d.) Hemoglobin >/= 80g/L (8.0g/dL) within 2 weeks of randomization. e.) Serum creatinine </= 2.0 x ULN f.) Total bilirubin </= 1.5 x ULN

6) (# 5 cont'd) f.) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </= 3 x ULN (</= 5 x ULN if liver metastases are present) g.) Glycosylated hemoglobin A1c (HbA1c) </= 9 % (hyperglycemia therapy permitted) h.) Prothrombin time (PT) or international normalized ratio (INR), or prothrombin activity and partial thromboplastin time(PTT) </= 1.5 x ULN. (Anticoagulation is allowed if a subject is on a stable dose of coumarin type anticoagulant or LMW heparin prior to randomization.)

7) 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.

8) Eastern Cooperative Oncology Group (ECOG) performance status 0-1

9) Ability to swallow whole sorafenib tablets.

10) Life expectancy of at least 12 weeks.

11) Signed and dated institutional review board (IRB) or independent ethics committee (IEC) approved informed consent form (ICF) before any protocol-specific screening procedures.

Exclusion Criteria:1) Metastatic Central Nervous System (CNS) from RCC.

2) Subjects who discontinued sunitinib 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 prior to randomization.

8) Inadequately controlled hypertension (defined as blood pressure of > 140 mm Hg systolic and/or > 90 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 (AHA) 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 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 [anti 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) Current active second malignancy other than non-melanoma skin cancers. Subjects are not considered to have a currently active malignancy if they have completed anti-cancer 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 agents.

22) Patients currently receiving and/or have received prior investigational drugs/vaccines (except sunitinib) within the past 30 days.

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Links
Registration Number: NCT00474786
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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