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Nivolumab With DC Vaccines for Recurrent Brain Tumors (AVERT)

This study has been terminated.
(Drug availability)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02529072
First Posted: August 19, 2015
Last Update Posted: October 2, 2017
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.
Collaborators:
Bristol-Myers Squibb
Duke Cancer Institute
Information provided by (Responsible Party):
Gary Archer Ph.D., Duke University Medical Center
  Purpose
Patients will be randomized to one of two treatment arms - Group I and Group II. Group I will receive nivolumab monotherapy until surgical resection, and Group II will receive nivolumab alone and with DC vaccine therapy until surgical resection. During surgical resection blood and tumor samples will be assessed and compared. Following surgery, both groups will continue to receive DC vaccines (total of 8) and nivolumab therapy until confirmed progression.

Condition Intervention Phase
Malignant Glioma Astrocytoma Glioblastoma Drug: nivolumab Biological: DC Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: AVeRT: Anti-PD-1 Monoclonal Antibody (Nivolumab) in Combination With DC Vaccines for the Treatment of Recurrent Grade III and Grade IV Brain Tumors

Resource links provided by NLM:


Further study details as provided by Gary Archer Ph.D., Duke University Medical Center:

Primary Outcome Measures:
  • The safety of administering DC vaccines with nivolumab, as measured by the percentage of patients who experience unacceptable toxicity during combination treatment [ Time Frame: 12 months ]

    To assess the safety of the combination of DC vaccination and nivolumab, the percentage of patients who experience unacceptable toxicity during combination treatment (i.e. DC vaccination + nivolumab) will be tabulated.

    Unacceptable toxicity is defined as any grade 3, 4, or 5 adverse event that is possibly, probably, or definitely related to either nivolumab or DC vaccination treatment during concurrent treatment, or any Grade 2 drug-related uveitis or eye pain or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within the re-treatment period OR requires systemic treatment. In addition, any complication following resection (ex. excessive intracranial bleeding, delays in wound healing) that are prolonged longer than 4-6 weeks post-surgery will be considered an unacceptable toxicity.



Secondary Outcome Measures:
  • Survival of subjects treated with any protocol treatment (i.e. nivolumab or DC vaccines). [ Time Frame: 12 to 72 months ]
    Survival is defined as the time between first initiation of nivolumab treatment and death, or last follow-up if the patient remains alive. The Kaplan-Meier estimator will be used to describe the overall survival (OS) experience of all patients. Median OS will also be calculated. Patients who are not able to tolerate nivolumab and are removed from the study will not be included in these analyses. Patients for whom DC vaccines cannot be manufactured will not be included in the survival analyses.

  • Progression Free Survival (PFS) of subjects treated with any protocol treatment (i.e. nivolumab or DC vaccines). [ Time Frame: 6 to 48 months ]
    PFS is defined as the time between treatment initiation and initial progression or death, or date of last follow-up if the patient remains alive without disease progression. The Kaplan-Meier estimator will be used to describe the PFS experience of all patients. Median PFS will also be calculated. Patients who are not able to tolerate nivolumab and are removed from the study will not be included in these analyses. Patients for whom DC vaccines cannot be manufactured will not be included in the survival analyses.


Enrollment: 7
Actual Study Start Date: January 2016
Estimated Study Completion Date: September 2018
Primary Completion Date: September 15, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group I
Patients will receive nivolumab 3 mg/kg IV every 2 weeks for 8 weeks followed by surgery. Following resection, nivolumab and DC vaccine will be administered every 2 weeks (± 1) for a total of 3 vaccines, followed by biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
Drug: nivolumab
Nivolumab is a fully human monoclonal antibody that targets the programmed death-1 (PD-1) cluster of differentiation 279 cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes. Binding of PD-1 to its ligands, programmed death-ligands 1 and 2, results in the down-regulation of lymphocyte activation. Inhibition of the interaction between PD-1 and its ligands promotes immune responses and antigen-specific T cell responses to both foreign antigens as well as self-antigens. Nivolumab is expressed in Chinese hamster ovary cells and is produced using standard mammalian cell cultivation and chromatographic purification technologies. The clinical study product is a sterile solution for parenteral administration.
Other Names:
  • BMS-936558
  • MDX1106
Biological: DC
DCs are potent immunostimulatory cells that continuously sample the antigenic environment of the host and specifically activate cluster of differentiation 4 positive (CD4+) and cluster of differentiation 8 positive (CD8+) T-cells and B-cells. They are at the crossroads of many of the elegant networks of the immune system, and DCs represent the most promising contemporary biologic entity for realizing the promise of immunotherapy. Potent immune responses and encouraging clinical results have been seen in Phase I and II human clinical trials in systemic cancers. Numerous animal studies and the investigator's institution's humans studies have demonstrated potent antitumor responses using DC-based immunotherapy against MGs.
Other Names:
  • DC vaccine
  • pp65 DC vaccine
  • Human CMV pp65-LAMP mRNA-pulsed autologous DCs
  • CMV pp65 DCs
Experimental: Group II
Patients will initially receive the fourth cycle of nivolumab then receive nivolumab 3 mg/kg IV and DC vaccine every 2 weeks for a total of 3 vaccines, and then surgery. Subsequent to surgery, the patient will resume biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.
Drug: nivolumab
Nivolumab is a fully human monoclonal antibody that targets the programmed death-1 (PD-1) cluster of differentiation 279 cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes. Binding of PD-1 to its ligands, programmed death-ligands 1 and 2, results in the down-regulation of lymphocyte activation. Inhibition of the interaction between PD-1 and its ligands promotes immune responses and antigen-specific T cell responses to both foreign antigens as well as self-antigens. Nivolumab is expressed in Chinese hamster ovary cells and is produced using standard mammalian cell cultivation and chromatographic purification technologies. The clinical study product is a sterile solution for parenteral administration.
Other Names:
  • BMS-936558
  • MDX1106
Biological: DC
DCs are potent immunostimulatory cells that continuously sample the antigenic environment of the host and specifically activate cluster of differentiation 4 positive (CD4+) and cluster of differentiation 8 positive (CD8+) T-cells and B-cells. They are at the crossroads of many of the elegant networks of the immune system, and DCs represent the most promising contemporary biologic entity for realizing the promise of immunotherapy. Potent immune responses and encouraging clinical results have been seen in Phase I and II human clinical trials in systemic cancers. Numerous animal studies and the investigator's institution's humans studies have demonstrated potent antitumor responses using DC-based immunotherapy against MGs.
Other Names:
  • DC vaccine
  • pp65 DC vaccine
  • Human CMV pp65-LAMP mRNA-pulsed autologous DCs
  • CMV pp65 DCs

  Show Detailed Description

  Eligibility

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.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-80 years of age
  • First or second recurrence of MG (WHO Grade III or IV glioma or astrocytoma) in surgically accessible areas with prior histologic diagnosis of MG
  • Bevacizumab-naïve - no prior exposure to Bevacizumab
  • Karnofsky Performance Status (KPS) of ≥ 70%
  • Radiation Therapy (RT) with ≥ 45 Gray (Gy) tumor dose, completed ≥ 8 weeks prior to study entry
  • Laboratory values must meet the following criteria:

    1. White Blood Count (WBC) ≥ 2000/microliters (uL)
    2. Neutrophils ≥ 1500/uL
    3. Platelets ≥ 100x103/uL
    4. Hemoglobin ≥ 9.0 g/dL
    5. Serum creatinine ≤ 1.5x the upper limit of normal (ULN) or creatinine clearance (CrCl)≥ 40 mL/min (using the Cockcroft-Gault formula) c. Female CrCl = (140 - age in years) x weight in kg x 0.85 /72 x serum creatinine in mg/dL d. Male CrCl = (140 - age in years) x weight in kg x 1.00/72 x serum creatinine in mg/dL
    6. Aspartate Aminotransferase (AST) ≤ 3x ULN
    7. Alanine Aminotransferase (ALT) ≤ 3x ULN
    8. Bilirubin≤ 1.5x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
    9. Subjects must have resting baseline O2 saturation by pulse oximetry of ≥ 92% at rest.
  • Patients of child bearing potential or with partners of child-bearing potential must practice recommended contraceptive methods to prevent pregnancy during treatment and for 5 months after the last dose of nivolumab for women, 7 months after the last dose of nivolumab for men, and for 6 months after the last dose of bevacizumab for subjects receiving bevacizumab.

Exclusion Criteria:

  • Contrast-enhancing tumor component crossing the midline, multi-focal tumor, or tumor dissemination (subependymal or leptomeningeal)
  • Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
  • Pregnant or need to breast feed during the study period (Negative human chorionic gonadotropin (β-HCG) test required), or unable to maintain use of contraception while on study and for 31 weeks after the last dose of nivolumab
  • Active infection requiring treatment or an unexplained febrile (> 101.5o F) illness
  • Known immunosuppressive disease, autoimmune disease or human immunodeficiency virus infection, Hepatitis B or Hepatitis C
  • Known allergy or hypersensitivity to tetanus, or any other tetanus or diphtheria toxoid-containing vaccine, or any component of this vaccine (i.e., aluminum phosphate, formaldehyde)
  • Known severe (Grade 3 or 4) infusion-related allergy or hypersensitivity to any monoclonal antibody
  • Previous radiation therapy with anything other than standard radiation therapy (such as previous stereotactic radiosurgery) or previous treatment with an immune checkpoint inhibitor (i.e., nivolumab, pembrolizumab, ipilimumab)
  • Unstable or severe intercurrent medical conditions such as severe heart (New York Association Class 3 or 4) or lung (FEV1 < 50%) disease, uncontrolled diabetes mellitus
  • Corticosteroid use > 4 mg/day at time of consent
  • Prior inguinal lymph node dissection.
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT02529072


Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Gary Archer Ph.D.
Bristol-Myers Squibb
Duke Cancer Institute
Investigators
Principal Investigator: Katherine Peters, MD, PhD Duke University
  More Information

Responsible Party: Gary Archer Ph.D., Assistant Professor, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT02529072     History of Changes
Other Study ID Numbers: Pro00065241
First Submitted: August 12, 2015
First Posted: August 19, 2015
Last Update Posted: October 2, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Glioblastoma
Brain Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vaccines
Antibodies, Monoclonal
Nivolumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents