Kidney Cancer | Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma (RCC)
Kidney Cancer research study
What is the primary objective of this study?
The goal of this clinical research study is to compare pazopanib to temsirolimus in the treatment of advanced clear-cell renal cell carcinoma. The safety of each drug will also be studied. Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells. Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells to die.
Who is eligible to participate?
Inclusion Criteria: 1. Pathologic confirmation of metastatic or locally advanced RCC with a major clear cell component. 2. Measurable disease by RECIST criteria. 3. Age >/= 18 years 4. ECOG performance status 0-2 or Karnofsky Performance Status >/= 60% 5. Meets criteria for poor-risk defined as 3 or more of the following: ECOG performance status 2, anemia (hemoglobin lower than reference range), elevated serum LDH > 1.5x upper limit of normal (ULN), hypercalcemia (corrected serum calcium level > upper limit of normal), time from initial RCC diagnosis to registration on this trial < 1 year, and > 1 metastatic organ sites. 6. Adequate organ and marrow function within 14 days of registration as defined below: a) Absolute neutrophil count >/=1,500/µL b) Platelets >/=100,000/µL c) Hgb >/= 9.0 g/dL (transfusion allowed) d) Renal: serum creatinine </= 1.5 x ULN or calculated CrCl >/= 40 cc/min and random urine protein:creatinine ratio (UPC) < 1 or 24-hr urine protein < 1g e) Liver: total bilirubin </= 1.5 mg/dl; AST (SGOT) and ALT (SGPT) </= 2.5 x ULN for subjects without evidence of liver metastases, </= 5 x ULN for subjects with documented liver metastases f) INR </= 1.2 x ULN; PTT </= 1.5 x ULN. Therapeutic anticoagulation with warfarin is allowed if target INR </= 3 on a stable dose of warfarin or on a stable dose of LMW heparin for > 2 weeks (14 days) at time of randomization. 7. Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test within 14 days of study registration. Pregnancy test must be repeated if performed > 14 days before starting study drug. Exclusion Criteria: 1. Prior malignancy, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 2 years 2. Prior targeted therapy (anti-VEGF agents or mTOR inhibitors) including adjuvant therapy, and prior chemotherapy for mRCC. However, prior immunotherapy (cytokines or vaccines) is allowed. 3. Any experimental drug while on this study; however, concomitant bone targeted therapy (bisphosphonates or the anti-RANK ligand denosumab) is allowed. 4. Uncontrolled brain metastases and infections. Patients with brain metastases treated with Gamma Knife (GK) or whole brain radiation within 24 hours of registration. 5. History of stroke within 6 months of registration 6. Clinically significant cardiovascular disease, defined as myocardial infarction (or unstable angina) within 6 months of registration, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac dysrhythmia refractory to medical management. However, treated and controlled or stable/not clinically significant cardiovascular disease is allowed per evaluation by cardiologist. 7. Uncontrolled hypertension (home blood pressure readings are permitted) or prior history of hypertensive crisis or hypertensive encephalopathy; however, treatment of hypertension with medications is permitted. 8. History of uncontrolled hemoptysis (>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 9. Significant vascular disease including aortic aneurysm, aortic dissection. 10. Symptomatic peripheral vascular disease 11. Pregnancy 12. HIV-positive patients receiving combination anti-retroviral therapy 13. Coagulopathy or bleeding diathesis 14. Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital) 15. Major surgery within 28 days prior to registration 16. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device within 7 days prior to starting drug 17. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study registration 18. Serious non-healing wound 19. Baseline QTcB >/= 470 msec.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Pazopanib800 mg by mouth daily in 4 week study cycle.
Drug:Temsirolimus25 mg by vein infused over 30-60 minutes every week in 4 week study cycle.
Behavioral:Quality of Life AssessmentCompletion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.
Drug:Benadryl25 to 50 mg by vein approximately 30 minutes before the start of each dose of temsirolimus.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
PazopanibPazopanib 800 mg by mouth daily. Quality of Life Assessment - Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.
TemsirolimusTemsirolimus 25 mg by vein infused over 30-60 minutes weekly. Benadryl 25 to 50 mg by vein approximately 30 minutes before the start of each dose of temsirolimus. Quality of Life Assessment - Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.
Active, not recruiting
Start Date: October 24, 2012
Completed Date: October 2019
Phase: Phase 2
Primary Outcome: Progression Free Survival (PFS)
Secondary Outcome: Overall Survival (OS)
Study sponsors, principal investigator, and references
Principal Investigator: Amado Zurita, MD
Lead Sponsor: M.D. Anderson Cancer Center