Bevacizumab, Autologous Tumor/DC Vaccine, IL-2 and IFNα-2b in Metastatic Renal Cell Carcinoma (RCC) Patients
Condition: Metastatic Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: DC vaccine; Bevacizumab; IL-2; IFN
Intervention description: DC Vaccine therapy 10E7 intranodally every cycle; Bevacizumab 10mg/kg iv every 2 weeks; IL-2 18 MiU/m2 CI 5 days; IFN 6 MiU subc TIW
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Renal Cell Carcinoma

Summary:

      Immune therapies, such as a IL-2, for metastatic renal cell carcinoma (mRCC) are designed to
      mobilize immune effector cells that recognize and destroy cancer. The investigators have
      recently observed a 50% objective response rate (16% CR) in mRCC patients treated with
      autologous tumor lysate -dendritic cell (DC)-vaccine, IL-2 and interferon alfa (IFN). New
      agents inhibiting vascular endothelial growth factor (VEGF) pathways have demonstrated
      significant benefit in mRCC patients as well, but rarely induce CRs. High blood VEGF is
      associated with poor response to IL-2 and can cause tumor specific immune dysregulation. To
      test whether complementary mechanisms of immune activation and disruption of regulatory
      pathways enhance outcome the investigators plan to treat 24 mRCC patients in a phase II trial
      using bevacizumab, DC vaccine, IL-2, and IFN. Observations from this project will be used in
      the development of novel cancer therapies which, if successful, will decrease the burden of
      cancer on the public.

      The investigators propose to determine 1) the objective clinical response rate to treatment
      and progression free survival, 2) the clinical and autoimmune related toxicity profile of
      therapy, and 3) the treatment related tumor-specific immune response and the relationship of
      tumor-specific immune response and objective clinical response.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed metastatic renal cell carcinoma with measurable disease.

          2. Adequate tumor tissue properly stored and available to produce lysate for a minimum of
             three vaccine preparations.

          3. Patients must be at least 4 weeks from their last therapy (tyrosine kinase inhibitors,
             immunotherapy, radiation, surgery or chemotherapy (6 weeks for nitrosureas) and
             recovered from all ill effects.

          4. Have measurable disease.

          5. Patients must be at least 4 weeks from major surgery, 1 week from minor surgery, and
             recovered from all ill effects.

          6. Karnofsky Performance Status ≥80%.

          7. Adequate end organ function:

          8. Women should not be lactating and, if of childbearing age, have a negative pregnancy
             test within two weeks of entry to the study.

          9. Appropriate contraception in both genders.

         10. The patient must be competent and have signed informed consent.

         11. Patients may have received one prior therapy with targeted therapies (e.g. sorafenib
             and sunitinib).

        Exclusion Criteria:

          1. Patients who have previously received bevacizumab or IL-2 are not eligible.

          2. Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive
             cancer such as cervical CIS, superficial bladder cancer without local recurrence or
             breast CIS.

          3. In patients with a prior history of invasive malignancy, less than five years in
             complete remission.

          4. Positive serology for HIV, hepatitis B or hepatitis C which should be confirmed with
             antigenemia.

          5. Significant co-morbid illness such as uncontrolled diabetes or active infection that
             would preclude treatment on this regimen.

          6. Use of corticosteroids or other immunosuppression (if patient had been taking
             steroids, at least 2 weeks must have passed since the last dose). Inhaled steroids >
             1000mcg beclomethasone per day or its equivalent.

          7. History of inflammatory bowel disease or other serious autoimmune disease. (Not
             including thyroiditis and rheumatoid arthritis).

          8. Patients with organ allografts.

          9. Uncontrolled hypertension (BP >150/100 mmHg).

         10. Proteinuria dipstick > 3+ or > 2gm/24 hours, or a urine protein:creatinine ratio > 1.0
             at screening.

         11. Major surgery, open biopsy, significant traumatic injury within 28 days of starting
             treatment or anticipation of need for major surgical procedure during the course of
             the study.

         12. Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
             prior to starting treatment. Central venous catheter placements are permitted.

         13. History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess
             within 6 months prior to starting treatment.

         14. Serious, non-healing wound, ulcer, or bone fracture.

         15. History of tumor-related or other serious hemorrhage, bleeding diathesis, or
             underlying coagulopathy.

         16. History of deep venous thrombosis, or other thrombotic event within the past six
             months or clinically significant peripheral vascular disease.

         17. Inability to comply with study and/or follow-up procedures.