Phase II Study of Alternating Sunitinib and Temsirolimus
Condition: Metastatic Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Sunitinib; Temsirolimus
Intervention description: Sunitinib 50mg by mouth daily for 4 weeks followed by a two week rest; Temsirolimus 25mg IV weekly for 4 weeks followed by a two week rest
Intervention MeSH terms: Sirolimus; Sunitinib; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Renal Cell Carcinoma; sunitinib; alternating; temsirolimus

Summary:

      In the past 5 years, treatment for metastatic Renal Cell Carcinoma (mRCC) has focused on
      agents directed at blocking tumor and vascular growth pathways. Sunitinib blocks the vascular
      endothelial growth factor receptor (VEGFr) and temsirolimus is an inhibitor of mammalian
      target of rapamycin (mTOR). Both sunitinib and temsirolimus are FDA approved agents for mRCC.
      When agents like these are given together, the toxicity increases but they can be given
      safely, at full doses, sequentially. We hypothesize that alternating these agents will double
      the progression free survival (PFS) of the agents when given sequentially.
    

Eligibility criteria:

        Inclusion Criteria

          -  Histologically confirmed metastatic renal cell cancer with evaluable disease.

          -  Patients must be at least 2 weeks from their last immunotherapy, surgery or
             chemotherapy (6 weeks for nitrosureas) and recovered from all ill effects.

          -  Karnofsky Performance Status ≥60%

          -  Life expectancy ≥ twelve weeks

          -  Adequate end organ function:

        Cardiac Left ventricular ejection fraction (LVEF) ≥lower limit of institutional normal
        (LLN) as assessed by echocardiography (ECHO) . The same modality used at baseline must be
        applied for subsequent evaluations.

          -  Women should not be lactating and, if of childbearing age, have a negative pregnancy
             test within two weeks of entry to the study and practicing acceptable forms of birth
             control

          -  Appropriate Contraception in both sexes

          -  The patient must be competent and signed informed consent.

        EXCLUSION CRITERIA

          -  Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive
             cancer such as cervical CIS, superficial bladder cancer without local recurrence,
             breast CIS.

          -  In patients with a prior history of invasive malignancy, less than five years in
             complete remission.

          -  Have evidence of significant co-morbid illness such as uncontrolled diabetes,
             hypertension or active infection that would preclude treatment on this regimen.

          -  Prior treatment with either sunitinib or temsirolimus

          -  Clinically significant gastrointestinal abnormalities

          -  Presence of uncontrolled infection.

          -  Prolongation of corrected QT interval (QTc) > 480 milliseconds - History of any one or
             more of the following cardiovascular conditions within the past 12 months:

               1. Cardiac angioplasty or stenting

               2. Myocardial infarction

               3. Unstable angina

               4. Coronary artery by-pass graft surgery

               5. Symptomatic peripheral vascular disease

               6. Class III or IV congestive heart failure, as defined by the New York Heart
                  Association (NYHA)

          -  History of cerebrovascular accident (CVA) including transient ischemic attack (TIA)
             within the past 12 months.

          -  History of pulmonary embolism or untreated deep venous thrombosis (DVT)within the past
             6 months. Note: Subjects with recent DVT who have been treated with therapeutic
             anticoagulating agents for at least 6 weeks are eligible.

          -  Poorly controlled hypertension [defined as systolic blood pressure (SBP) of

             ≥150 or diastolic blood pressure (DBP) of ≥ 90. Note: Initiation or adjustment of
             antihypertensive medication(s) is permitted prior to study entry.

          -  Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
             presence of any non-healing wound, fracture, or ulcer.

          -  Evidence of active bleeding or bleeding diathesis

          -  Hemoptysis within 6 weeks of first dose of study drug.

          -  Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

          -  Any serious and/or unstable pre-existing medical, psychiatric, or other conditions
             that could interfere with subject's safety, obtaining informed consent or compliance
             to the study.

          -  Is now undergoing and/or has undergone in the 14 days immediately prior to first dose
             of study drug any minor surgeries (i.e. skin biopsy, tooth extraction, etc.) and
             recovered from all ill effects.

          -  Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
             progressing in severity.

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to sunitinib or temsirolimus.

          -  Untreated brain metastasis. (Brain metastases that are stable based on radiographic
             evidence 4 weeks after radiation and/or surgery are permitted).