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

October 28, 2015 updated by: Dartmouth-Hitchcock Medical Center

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)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth-Hitchcock Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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 Names:
  • Avastin
Biological: IL-2
IL-2 18 MiU/m2 CI 5 days
Biological: IFN
IFN 6 MiU subc TIW

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 5 years
median progression free survival
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure of Percent of CD4 and CD8 Lymphocyte Subsets
Time Frame: Baseline, day 28, day 70
percent of CD4 and CD8 positive lymphocyte subsets
Baseline, day 28, day 70
Clinical Response
Time Frame: Day 70
clinical response by RECIST 1.1
Day 70

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dartmouth-Hitchcock Medical Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Marc S Ernstoff, MD, Dartmouth-Hitchcock Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (ACTUAL)

January 1, 2013

Study Completion (ACTUAL)

January 1, 2013

Study Registration Dates

First Submitted

June 2, 2009

First Submitted That Met QC Criteria

June 3, 2009

First Posted (ESTIMATE)

June 4, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

December 1, 2015

Last Update Submitted That Met QC Criteria

October 28, 2015

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D0708
  • R01CA095648 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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