Nivolumab With DC Vaccines for Recurrent Brain Tumors

• Status: Completed
• Trial end date: 2019-12-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gary Archer Ph.D.
• Collaborators: Bristol-Myers Squibb; Duke Cancer Institute
• Treatments: Antibodies, Monoclonal; Nivolumab; Vaccines

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.