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

NCT00913913 | Terminated Phase 2 Results DMC

• 2 other identifiers: D0708R01CA095648
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Renal Cell Carcinoma

Keywords

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  median progression free survival

  5 years

Secondary Outcomes (1)

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

  5 years

Other Outcomes (2)

• Measure of Percent of CD4 and CD8 Lymphocyte Subsets

  Baseline, day 28, day 70

• Clinical Response

  Day 70

Study Arms (1)

bevacizumab,IL-2, IFN, DC vaccine

EXPERIMENTAL

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; Drug: Bevacizumab; Biological: IL-2; Biological: IFN

Interventions

DC vaccine BIOLOGICAL

DC Vaccine therapy 10E7 intranodally every cycle

bevacizumab,IL-2, IFN, DC vaccine

Bevacizumab DRUG

Bevacizumab 10mg/kg iv every 2 weeks

Also known as: Avastin

bevacizumab,IL-2, IFN, DC vaccine

IL-2 BIOLOGICAL

IL-2 18 MiU/m2 CI 5 days

bevacizumab,IL-2, IFN, DC vaccine

IFN BIOLOGICAL

IFN 6 MiU subc TIW

bevacizumab,IL-2, IFN, DC vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Related Publications (1)

• 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.

  PMID: 17255302 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

lentiviral minigene vaccine of COVID-19 coronavirus; Bevacizumab; Interleukin-2

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Lymphokines; Biological Factors

Limitations and Caveats

This study closed early due to difficulty enrolling patients with enrollment limited due to new competing therapies. Though enrollment numbers per statistical design were not met, the primary objective may still be reviewed.

Results Point of Contact

• Title: Dr. Marc Ernstoff
• Organization: Dartmouth-Hitchcock Medical Center

marc.s.ernstoff@hitchcock.org

603-650-5534

Study Officials

• Marc S Ernstoff, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2009
• First Posted: June 4, 2009
• Study Start: February 1, 2009
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: December 1, 2015
• Results First Posted: December 1, 2015

Record last verified: 2014-02

Locations

US (1)