Personalized Targeted Inhibitors Treatment in Renal Cell Cancer
Condition: Carcinoma, Renal Cell
MeSH terms: Carcinoma, Renal Cell
Intervention: Sunitinib; Temsirolimus; Sorafenib; Pazopanib; Everolimus; Axitinib
Intervention description: One 50-mg capsule taken orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off; 25 mg by an IV infusion over 30-60 minutes, once a week; 400 mg (2 tablets) orally twice daily without food; 800 mg orally once a day without food, at least 1 hour before or 2 hours after a meal; 10 mg orally once daily with or without food; 5 mg orally twice daily
Intervention MeSH terms: Sirolimus; Everolimus; Temsirolimus; MTOR Inhibitors; Sorafenib; Sunitinib; Axitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Renal Cell Carcinoma; RCC; Personalized therapy; targeted inhibitors

Summary:

      This is for subjects with metastatic Renal Cell Cancer (RCC). There are four Food and Drug
      Administration (FDA) approved drugs for first-line therapy of Renal Cell Cancer (RCC) and two
      for second-line therapy. Each of these drugs targets a specific molecular pathway. At present
      oncologists select therapy based on current guidelines. There is a new method for trying to
      use biomarker information from the subject's tumor to select the best drug to treat the
      subject. This process is investigational, which is why this study is being done.

      Biomarkers are genes, proteins and other molecules that affect how cancer cells grow,
      multiply, die and respond to other compounds in the body. These biomarkers build a tumor
      profile or "fingerprint" of the subject's tumor. A new focus in cancer care is personalized
      treatment, where doctors select a drug based on the subject's tumor's unique "fingerprint"
      which is more likely to be effective in fighting the tumor. Selecting the treatment the
      subject is more likely to respond to requires a thorough understanding of the relationship
      between biomarker and treatment effect. The PI wants to gather data to understand that
      relationship to help treat future cancer patients. The purpose of this study is to evaluate
      efficacy of treatments that are selected based on tumor profiles.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects may be included in the study only if they meet all of the following inclusion
             criteria:

               -  Pathologically confirmed renal cell carcinoma.

               -  No prior systemic and/or investigative therapy of any kind.

                    -  Patients with primary tumor in place are strongly encouraged to undergo
                       nephrectomy prior to initiation of study agent.

                    -  Prior palliative radiotherapy to metastatic lesion(s) is permitted. Patient
                       must have adequately recovered from the acute toxicities of this treatment.

                    -  All major surgery of any type and/or radiotherapy must be completed at least
                       4 weeks prior to registration.

               -  Must have progressive metastatic disease

               -  ECOG performance status ≤2

               -  Women of childbearing potential and male patients must use acceptable methods of
                  contraception-tubal ligation, vasectomy, barrier contraceptive with
                  spermicide-while on study and for 3 months after the last dose of study therapy.
                  Oral, implantable, or injectable contraceptives may be affected by cytochrome
                  P450 interactions, and are therefore not considered effective for this study.

               -  Age ≥18 years

               -  Required Initial Laboratory Values:

                    -  Granulocytes ≥1,500/µL

                    -  Platelet Count ≥100,000/µL

                    -  Hemoglobin ≥9 g/dL

                    -  AST/ALT ≤ 2.5 times the upper limit of normal (ULN)

                    -  Alk. Phos.≤ 2.5 x ULN

                    -  Serum bilirubin ≤ 1.5 x ULN

                    -  Amylase/Lipase within normal range

                    -  Urinalysis≤ 1+ protein

                    -  T3T4 TSH - within normal range

                    -  Pregnancy test for women - Negative

                    -  Serum creatinine ≤ 1.5 x ULN

                    -  Electrocardiogram (ECG) - no active ischemia

                    -  Echocardiogram ejection fraction ≥40%

                    -  Pulmonary function tests

                    -  Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting
                       triglycerides ≤2.5 x ULN. NOTE: In case one or both of these thresholds are
                       exceeded, the patient can only be included after initiation of appropriate
                       lipid lowering medication.

               -  Signed informed consent prior to the performance of any study-specific procedures

        Exclusion Criteria:

          -  Ongoing hemoptysis, or cerebrovascular accident within 12 months prior to study entry,
             or peripheral vascular disease with claudication occurring upon walking less than one
             city block, or history of clinically significant bleeding.

          -  Deep venous thrombosis or pulmonary embolus within 12 months prior to study entry and
             no ongoing need for full-dose oral or parenteral anticoagulation. For maintenance of
             catheter patency daily prophylactic aspirin or low-dose coumadin (1-2 mg) is allowed.

          -  Evidence of current central nervous system (CNS) metastases. All patients must undergo
             a CT scan of the brain (with contrast, if possible) within 42 days prior to
             registration. Any imaging abnormality indicative of active CNS metastases will exclude
             the patient from the study.

          -  Significant cardiovascular disease defined as congestive heart failure (New York Heart
             Association Class II, II or IV) angina pectoris requiring nitrate therapy, or recent
             myocardial infarction (within the preceding 6 months prior to study entry).

          -  Uncontrolled hypertension (defined as blood pressure of ≥160 mmHg systolic and/or ≥90
             mmHg diastolic on medication). Document over 48 hours with minimum of 3 readings.

          -  Ongoing requirement for systemic corticosteroid therapy (except replacement therapy
             for adrenal insufficiency) or other immunosuppressants are not permitted. Topical
             and/or inhaled steroids are allowed.