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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00913913
Recruitment Status : Terminated (low accrual not allowing site to meeting statistical endpoints)
First Posted : June 4, 2009
Results First Posted : December 1, 2015
Last Update Posted : December 1, 2015
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Metastatic Renal Cell Carcinoma Biological: DC vaccine Drug: Bevacizumab Biological: IL-2 Biological: IFN Phase 2

Detailed Description:
All eligible patients will receive a total of five treatment weeks, each consisting of approximately 5 days. Prior to therapy, patients will undergo apheresis for DC preparation. DC-Tumor vaccines will be frozen in 90% pooled human AB serum/ 10% DMSO to be used for treatment Patients will be dosed with bevacizumab (10mg/kg, Genentech) intravenously every two weeks beginning four weeks prior to the first vaccine. Each treatment week includes ultrasound guided intranodal DC-vaccine injection (1 X 107 cells/1mL), followed by 5 days of continuous intravenous infusion of IL-2 (18 MiU/m2, Novartis), and three subcutaneous injections of IFNa-2b (6 MiU, Schering -Plough Corp.) (every other day). The first two treatment weeks, the induction phase, will be separated by a 9 day rest. Three additional treatment weeks, the maintenance phase, will be separated by 23 rest days.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of VEGF Blockade With Bevacizumab Combined With Autologous Tumor/Dendritic Cell Vaccine (DC Vaccine), Interleukin-2 (IL-2) and Interferon-α-2b (IFNα-2b) in Patients With Metastatic Renal Cell Carcinoma (RCC)
Study Start Date : February 2009
Actual Primary Completion Date : January 2013
Actual Study Completion Date : January 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines
Drug Information available for: Bevacizumab

Arm Intervention/treatment
Experimental: bevacizumab,IL-2, IFN, DC vaccine
Patients will be dosed with bevacizumab (10mg/kg) intravenously every two weeks beginning four weeks prior to the first vaccine. Each treatment week includes ultrasound guided intranodal DC-vaccine injection (1 X 107 cells/1mL), followed by 5 days of continuous intravenous infusion of IL-2 (18 MiU/m2), and three subcutaneous injections of IFNa-2b (6 MiU) (every other day)
Biological: DC vaccine
DC Vaccine therapy 10E7 intranodally every cycle

Drug: Bevacizumab
Bevacizumab 10mg/kg iv every 2 weeks
Other Name: Avastin

Biological: IL-2
IL-2 18 MiU/m2 CI 5 days

Biological: IFN
IFN 6 MiU subc TIW

Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 5 years ]
    median progression free survival

Secondary Outcome Measures :
  1. To Characterize the Number of Participants With Clinical and Autoimune Related Toxicity of Treatment [ Time Frame: 5 years ]
    To characterize the clinical and autoimmune related toxicity profile of the combined treatment regimen using CTCAE 3. Toxicity reported are those expected from high dose IL-2 and were not considered adverse events.

Other Outcome Measures:
  1. Measure of Percent of CD4 and CD8 Lymphocyte Subsets [ Time Frame: Baseline, day 28, day 70 ]
    percent of CD4 and CD8 positive lymphocyte subsets

  2. Clinical Response [ Time Frame: Day 70 ]
    clinical response by RECIST 1.1

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00913913

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United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
National Cancer Institute (NCI)
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Principal Investigator: Marc S Ernstoff, MD Dartmouth-Hitchcock Medical Center
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Responsible Party: Dartmouth-Hitchcock Medical Center Identifier: NCT00913913    
Other Study ID Numbers: D0708
R01CA095648 ( U.S. NIH Grant/Contract )
First Posted: June 4, 2009    Key Record Dates
Results First Posted: December 1, 2015
Last Update Posted: December 1, 2015
Last Verified: February 2014
Keywords provided by Dartmouth-Hitchcock Medical Center:
Renal Cell Carcinoma
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors