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About
This is a phase 1b study of P30-linked EphA2, CMV pp65, and survivin vaccination (collectively called the P30-EPS vaccine) in HLA-A*0201 positive patients with a newly diagnosed, unmethylated, and untreated World Health Organization (WHO) grade IV malignant glioma.
Full description
This is a phase 1b study of P30-linked EphA2, CMV pp65, and survivin vaccination (collectively called the P30-EPS vaccine) in HLA-A*0201 positive patients with a newly diagnosed, unmethylated, and untreated World Health Organization (WHO) grade IV malignant glioma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke, is planned to address the following primary objective: Evaluate the safety profile of a cancer vaccine comprised of P30-linked EphA2, CMV pp65, and survivin peptides.
A maximum of 36 patients with a newly diagnosed, previously untreated WHO grade IV malignant glioma that is MGMT promoter unmethylated will be treated in this study after undergoing standard of care surgical resection followed by 6 weeks of radiation therapy (XRT) with concomitant temozolomide (TMZ) and providing informed consent. Patients will receive seven P30 linked-EphA2, -CMV pp65, and -survivin (P30-EPS) peptide vaccines over two phases. The first 5 will be given during the Priming Phase (day 1 through day 22). The final 2 will be given during the Booster Phase (day 84 [± 2 days] and day 140 [± 2 days]). During the Booster Phase on Day 84, patients will also be given 20ug/kg Hiltonol® injections to administer at home every 2 weeks until they return on Day 140. Blood will be drawn throughout the study to investigate the immune response to P30-EPS vaccination. The study will enroll two patient strata: patients who are CMV seronegative and patients who are CMV seropositive. Within each stratum, cohorts of 3 patients will initially be accrued to the study to assess the toxicity associated with the vaccine. The starting dose of P30-EPS is 300 μg/peptide/dose, and the dose will be escalated to 400 μg/peptide/dose. In the event of unacceptable dose-limiting toxicity, the dose will be de-escalated to 200 μg/peptide/dose (dose level minus one). Acute toxicity monitoring will focus on dose-limiting toxicities, as defined in Section 9.1.2 of the protocol, occurring between vaccine 1 and 30 days after vaccine 5. The most common side effects of peptide vaccines are redness or swelling at the injection site, local changes to the texture of your skin (hardening) at the injection site, itching, allergic reactions, and a potentially serious side effect called cytokine release syndrome. The most common side effects of Hiltonol® are reactions at the injection site and flu-like symptoms.
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Inclusion and exclusion criteria
Inclusion Criteria
Exclusion Criteria
Patients with known potentially anaphylactic allergic reactions to gadolinium-diethylenetriaminepentaacetic acid (DTPA), or any component of the tetanus-diphtheria vaccine.
Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of multifocal disease, or leptomeningeal disease.
Areas of high-grade glioma outside the original radiation field on the post XRT/TMZ MRI.
Patients who cannot undergo MRI.
Severe, active comorbidity, including any of the following:
Co-medication that may interfere with study results (e.g., immuno-suppressive agents other than corticosteroids).
Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin. (Treatment with tamoxifen or aromatase inhibitors or other hormonal therapy that may be indicated in prevention of prior cancer disease recurrence, are not considered current active treatment.)
Patients are not permitted to have had any other conventional therapeutic intervention other than surgery, steroids, and standard of care chemoradiation prior to enrollment.
Patients who received previous inguinal lymph node dissection or had radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies to treat a CNS tumor will be excluded.
Current, recent (within 4 weeks of the administration of this study agent), or planned participation in an experimental drug study.
Known history of autoimmune disease (with the exceptions of medically-controlled hypothyroidism and Diabetes Mellitus).
Primary purpose
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Interventional model
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24 participants in 1 patient group
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Central trial contact
Mustafa Khasraw, MBChB, MD, FRCP, FRACP; Stevie Threatt
Data sourced from clinicaltrials.gov
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