This phase I trial studies the side effects of vaccine therapy and temozolomide in treating patients with glioma expressing isocitrate dehydrogenase 1 (IDH1) gene that has returned (come back) after a period of improvement (recurrent). Vaccines made from peptides may help the body build an effective immune response to kill tumor cells that express IDH1. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vaccine therapy with temozolomide may be a better treatment for recurrent glioma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02193347.
PRIMARY OBJECTIVES:
I. To assess the safety of the PEPIDH1M vaccine (IDH1R132H-specific peptide vaccine PEPIDH1M) alone and in combination with adjuvant TMZ (temozolomide) and/or radiation therapy (XRT)/TMZ in adult patients with progressive, resectable World Health Organization (WHO) grade II gliomas that are confirmed grade II or transition to a higher grade glioma at the time of surgery.
SECONDARY OBJECTIVES:
I. To assess the immunogenicity of the PEPIDH1M vaccine with adjuvant TMZ using enzyme-linked immunosorbent spot (ELIspot).
TERTIARY OBJECTIVES:
I. To describe progression-free survival (PFS) and overall survival (OS).
II. To determine if ELIspot results after vaccination predict PFS or OS.
III. To estimate radiographic response rate prior to surgical resection and PFS after resection using Revised Assessment in Neuro-Oncology (RANO) criteria.
IV. To determine if tumors are IDH1 negative by immunohistochemical analysis and microarray analysis at the time of post-vaccine surgery.
V. To characterize immunologic cell infiltrate in tumors at the time of post-vaccine surgery.
VI. To determine if tumor-specific circulating deoxyribonucleic acid (DNA) containing the c.395G > A (R132H) mutation can be detected in plasma before, during, and after study drug treatment.
VII. To determine if 2-hydroxyglutarate (2-HG), a metabolite specifically produced by tumors with IDH R132H, can be detected in plasma by mass spectrometry before, during, and after study drug treatment.
VIII. To explore the impact of PEPIDH1M vaccination on genetic alternations, differential protein expressions or post-translational modifications (PTMs) using quantitative proteomic strategies in patient-derived samples.
IX. To demonstrate quantitative repeatable measures of metabolism change in IDH1+ gliomas via a standardized magnetic resonance spectroscopy (MRS) protocol, patients will be scanned on the research magnetic resonance (MR) scanner to establish same-day and longitudinal metabolite coefficient of variance and possible longitudinal metabolite changes.
OUTLINE:
INITIAL VACCINE: Patients receive IDH1R132H-specific peptide vaccine PEPIDH1M in the left and right groin area intradermally (ID) on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity. Patients may receive tetanus toxoid vaccine boost ID one day prior to the first PEPIDH1M peptide vaccine.
SURGERY: Within 7-12 days after the third PEPIDH1M peptide vaccine, patients undergo surgical resection.
VACCINE AND CHEMOTHERAPY: Patients experiencing stable histological grade at recurrence then receive IDH1R132H-specific peptide vaccine PEPIDH1M in the left and right groin area ID on day 22 and temozolomide orally (PO) on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with higher grade gliomas undergoing radiation therapy (RT) receive vaccine #4 prior to RT, vaccine #5 after 4 weeks, and vaccine #6 at the end of RT. Patients then receive vaccines monthly on day 22 for up to 15 doses.
After completion of study treatment, patients are followed up at 1 month and then periodically.
Lead OrganizationDuke University Medical Center
Principal InvestigatorKatherine Barnett Peters
