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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00913913
First received: June 2, 2009
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Metastatic Renal Cell Carcinoma
Biological: DC vaccine
Drug: Bevacizumab
Biological: IL-2
Biological: IFN
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • To determine the objective clinical response rate and progression free survival (PFS) to this combined treatment regimen. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To characterize the clinical and autoimmune related toxicity profile of the combined treatment regimen. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • In relevant immune pathways, to measure treatment-related tumor-specific immune responses and to examine the relationship between tumor-specific immune response and objective clinical response in RCC patients treated with this regimen [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: February 2009
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00913913

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: Marc S Ernstoff, MD Dartmouth-Hitchcock Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00913913     History of Changes
Other Study ID Numbers: D0708, R01CA095648
Study First Received: June 2, 2009
Last Updated: November 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dartmouth-Hitchcock Medical Center:
Renal Cell Carcinoma

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014