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Metastatic Renal Cell CarcinomaPhase 2NCT00913913

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

A Phase 2 study testing DC vaccine, Bevacizumab and IL-2 in people with Metastatic Renal Cell Carcinoma, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Renal Cell Carcinoma
What is being tested?
DC vaccine, Bevacizumab and IL-2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
Feb 2009to Jan 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed metastatic renal cell carcinoma with measurable disease.
  • Adequate tumor tissue properly stored and available to produce lysate for a minimum of three vaccine preparations.
  • 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.
  • Have measurable disease.
  • Patients must be at least 4 weeks from major surgery, 1 week from minor surgery, and recovered from all ill effects.
  • Karnofsky Performance Status ≥80%.
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  • Adequate end organ function:
  • Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study.
  • Appropriate contraception in both genders.
  • The patient must be competent and have signed informed consent.
  • Patients may have received one prior therapy with targeted therapies (e.g. sorafenib and sunitinib).

Who cannot join

  • Patients who have previously received bevacizumab or IL-2 are not eligible.
  • 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.
  • In patients with a prior history of invasive malignancy, less than five years in complete remission.
  • Positive serology for HIV, hepatitis B or hepatitis C which should be confirmed with antigenemia.
  • Significant co-morbid illness such as uncontrolled diabetes or active infection that would preclude treatment on this regimen.
  • 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.
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  • History of inflammatory bowel disease or other serious autoimmune disease. (Not including thyroiditis and rheumatoid arthritis).
  • Patients with organ allografts.
  • Uncontrolled hypertension (BP >150/100 mmHg).
  • Proteinuria dipstick > 3+ or > 2gm/24 hours, or a urine protein:creatinine ratio > 1.0 at screening.
  • 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.
  • Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to starting treatment. Central venous catheter placements are permitted.
  • History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess within 6 months prior to starting treatment.
  • Serious, non-healing wound, ulcer, or bone fracture.
  • History of tumor-related or other serious hemorrhage, bleeding diathesis, or underlying coagulopathy.
  • History of deep venous thrombosis, or other thrombotic event within the past six months or clinically significant peripheral vascular disease.
  • Inability to comply with study and/or follow-up procedures.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

Other trials in United States

About this study

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)

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.

Read the 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.

Being tested
DC vaccine, Bevacizumab, IL-2, IFN
Keywords
Renal Cell Carcinoma
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DC vaccineBiological

    DC Vaccine therapy 10E7 intranodally every cycle

  • BevacizumabDrug

    Also called Avastin

    Bevacizumab 10mg/kg iv every 2 weeks

  • IL-2Biological

    IL-2 18 MiU/m2 CI 5 days

  • IFNBiological

    IFN 6 MiU subc TIW

Study groups in NCT00913913
Study groupRoleWhat they receive
bevacizumab,IL-2, IFN, DC vaccineExperimentalPatients 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)
Receives: Biological: DC vaccine; Drug: Bevacizumab; Biological: IL-2; Biological: IFN

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival

    median progression free survival

    Measured: 5 years

Secondary outcomes (1)

  1. To Characterize the Number of Participants With Clinical and Autoimune Related Toxicity of Treatment

    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.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2009 (estimated)
  2. Study startFeb 2009
  3. Primary completionJan 2013
  4. Study completionJan 2013

Why it stopped: low accrual not allowing site to meeting statistical endpoints

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00913913
Sponsor's protocol ID
D0708
Other IDs
R01CA095648
Status last verified
Feb 2014
First submitted
2 Jun 2009
Last updated
1 Dec 2015
Data monitoring committee
Yes

Publications

  • Ernstoff MS, Crocenzi TS, Seigne JD, Crosby NA, Cole BF, Fisher JL, Uhlenhake JC, Mellinger D, Foster C, Farnham CJ, Mackay K, Szczepiorkowski ZM, Webber SM, Schned AR, Harris RD, Barth RJ Jr, Heaney JA, Noelle RJ. Developing a rational tumor vaccine therapy for renal cell carcinoma: immune yin and yang. Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):733s-740s. doi: 10.1158/1078-0432.CCR-06-2064.

    PubMed 17255302

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DC vaccine, Bevacizumab and IL-2 in people with Metastatic Renal Cell Carcinoma, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00913913, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2015.

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