Avastin and Temsirolimus Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma
Condition: Renal Cell Carcinoma; Kidney Cancer
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: bevacizumab; temsirolimus
Intervention MeSH terms: Sirolimus; Bevacizumab; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: RCC; avastin; temsirolimus

Summary:

      This is a single-arm phase II trial evaluating the combination of avastin and temsirolimus in
      patients with metastatic renal cell cancer (RCC) including both histologically confirmed
      clear cell (cc) or non-clear cell (ncc) subtypes. Patients must have experienced disease
      progression or intolerable toxicity with a vascular endothelial growth factor (VEGF)-targeted
      tyrosine kinase inhibitor (TKI) (e.g. sorafenib, sunitinib, pazopanib). Only 2 prior VEGF
      therapies are allowed. The purpose of this research study is to evaluate efficacy of the
      combination against an historical control. Temsirolimus has been approved by the Food and
      Drug Administration (FDA) in the treatment of renal cell carcinoma. Avastin has been approved
      by the FDA for other types of cancers but not renal cell carcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed renal cell carcinoma in either primary or metastatic lesions.
             Non-clear histology will be allowed.

          -  Disease progression on a VEGF-targeted tyrosine kinase inhibitor as the most recent
             therapy or have experienced intolerable toxicity so as require discontinuation. Only
             one prior VEGF-targeted tyrosine kinase inhibitor.

          -  Must be off of VEGF-targeted tyrosine kinase inhibitor for 2 weeks or greater.

          -  One measurable lesion which is not curable by standard radiation therapy or surgery.

          -  The enrolling site must agree to obtain paraffin-embedded tumor blocks or at least 10
             unstained, paraffin-embedded slides for submission for correlative studies.

          -  18 years of age or older

          -  ECOG Performance Status of 0 or 1

          -  Baseline laboratory values as outlined in the protocol

          -  Life expectancy of greater than 3 months

          -  No prior malignancy diagnosed within the past three years, other than superficial
             basal cell and superficial squamous cell, or carcinoma in situ of the cervix.

        Exclusion Criteria:

          -  Known CNS disease, except for treated brain metastases

          -  Previously treated with avastin or mTOR inhibitors

          -  Other then VEFG-targeted TKI, patients may only have had prior immunotherapy or
             chemotherapy for stage IV disease

          -  History of allergic reaction to Chinese hamster ovary cell products, other recombinant
             antibodies, or compounds of similar chemical or biologic composition to avastin or
             temsirolimus

          -  History of bleeding diathesis or coagulopathy. Therapeutic anticoagulants are allowed

          -  Patients with clinically significant cardiovascular disease

          -  Patients receiving enzyme-inducing antiepileptic drugs or any other CYP3A4 inducer
             such as rifampin or St. John's wort

          -  No serious non-healing wound, ulcer or bone fracture

          -  No uncontrolled intercurrent illness including , but not limited to, ongoing active
             infection requiring parental antibiotics or psychiatric illness/social situations that
             would limit compliance with study requirements

          -  HIV-positive receiving combination anti-retroviral therapy

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study enrollment or anticipation of need for major surgical procedure during
             the course of the study

          -  Core biopsy or other minor surgical procedure, excluding placement of vascular access
             device, within 7 days prior to enrollment on study

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to study enrollment

          -  Known hypersensitivity to any component of avastin or temsirolimus

          -  Life expectancy of less than 12 weeks

          -  History of hemoptysis within 1 month prior to day 1