Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma (RCC)
Condition: Kidney Cancer
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: Pazopanib; Temsirolimus; Quality of Life Assessment; Benadryl
Intervention description: 800 mg by mouth daily in 4 week study cycle.; 25 mg by vein infused over 30-60 minutes every week in 4 week study cycle.; Completion of full assessment battery at baseline, prior to treatment then every 8 weeks at clinical evaluation.; 25 to 50 mg by vein approximately 30 minutes before the start of each dose of temsirolimus.
Intervention MeSH terms: Diphenhydramine; Sirolimus; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kidney cancer; Renal Cell Carcinoma; Poor-Risk Clear-Cell Renal Cell Carcinoma; RCC; Metastatic; Locally advanced; Complete response; CR; Partial Response; PR; Overall survival; OS; Time to progression; TTP; Pazopanib; GW786034; Temsirolimus; CCI-779; Torisel; Benadryl; Diphenhydramine; TemPa

Summary:

      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.

      This is an investigational study. Pazopanib and temsirolimus are both FDA approved and
      commercially available for the treatment of kidney cancer. It is investigational to compare
      the 2 drugs.

      Up to 90 patients will be enrolled in this study. All will be enrolled at MD Anderson.
    

Eligibility criteria:

        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.