Bevacizumab, Autologous Tumor/DC Vaccine, IL-2 and IFNα-2b in Metastatic Renal Cell Carcinoma (RCC) Patients

• Status: Terminated
• Trial end date: 2013-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Bevacizumab; Interleukin-2; Vaccines

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.