Personalized Mutation-Derived Tumor Vaccine, Poly ICLC, and NovoTTF-200A in Treating Patients with Glioblastoma

Status: Active

Description

This phase I trial studies the side effects and how well personalized mutation-derived tumor vaccine, poly ICLC, and NovoTTF-200A work in treating patients with glioblastoma. Vaccines made from tumor peptide or antigen may help the body build an effective immune response to kill tumor cells that express specific antigen. Poly ICLC may help to stimulate the immune system. NovoTTF-200A produces tumor treatment fields which are low intensity electric fields that may slow or stop cancer cells from multiplying and may cause them to die. Giving personalized mutation-derived tumor vaccine, poly ICLC, and NovoTTF-200A may work better than poly ICLC alone in treating patients with glioblastoma.

Eligibility Criteria

Inclusion Criteria

  • The subject must have histological confirmation of GBM (World Health Organization [WHO] grade IV)
  • The subject must have stable disease after treatment of radiation with concurrent chemotherapy; if the disease progresses while in the study the patient is allowed to continue on the study receiving the vaccine if the tumor gets controlled by other modality treatment(s)
  • The subject must have received maximal debulking surgery and undergo radiotherapy concomitant with temozolomide (45-70 gray [Gy])
  • The subject must have a life expectancy > 16 weeks
  • The subject must have a performance status of 0-2 as determined by criteria set forward by the Eastern Cooperative Oncology Group
  • The subject must have first vaccine treatment start date at least 4 weeks out from the last dose of concomitant temozolomide or radiotherapy
  • The subject must have archival tumor tissue that is sufficient quantity and quality for sequencing
  • The subject requires dexamethasone =< 4 mg daily on a stable dose
  • White blood count (WBC) > 3,000/ul (performed within 14 days prior to study)
  • Hemoglobin > 10 gm/dl (performed within 14 days prior to study)
  • Absolute neutrophil count >= 1500/mm^3 (performed within 14 days prior to study)
  • Platelet count >= 100,000/mm^3 (performed within 14 days prior to study)
  • Creatinine =< 2.5 mg/dL (performed within 14 days prior to study)
  • Alanine aminotransferase (ALT) < 3 times the upper limits of the institutional normal (performed within 14 days prior to study)
  • Aspartate aminotransferase (AST) < 3 times the upper limits of the institutional normal (performed within 14 days prior to study)
  • Alkaline phosphatase < 3 times the upper limits of the institutional normal (performed within 14 days prior to study)
  • Bilirubin < 3 times the upper limits of the institutional normal (performed within 14 days prior to study)
  • International normalized ratio (INR) < 2 if off of anticoagulation (performed within 14 days prior to study) patients on anticoagulation therapy with an INR > 2 may be enrolled at the discretion of the investigator if they have not had any episodes of severe hemorrhage
  • The subject must be deemed competent to give informed consent
  • The subject must agree to use two effective forms of contraception beginning at least four (4) weeks prior to study entry, and continuing to do so for the duration of their participation in the study

Exclusion Criteria

  • The subject has an implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias
  • The subject has an infra-tentorial tumor or multifocal disease
  • The subject has a history of hypersensitivity reaction to temozolomide or a history of hypersensitivity to dacarbazine (DTIC)
  • The subject is receiving any other investigational agents; patient is allowed to get another investigational agent and to continue receiving the vaccine only if the disease progresses while in the study and the other investigational agent is a reasonable choice to treat the patient
  • The subject has an active cancer being treated with chemotherapy at the time of screening
  • The subject has a history of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), chronic hepatitis B or hepatitis C or is otherwise reasonably suspected to meet criteria for the diagnosis of a known congenital or acquired disorder causing systemic immunosuppression
  • The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a known congenital or acquired disorder causing systemic immunosuppression; or the subject is currently receiving any drug or supplement which is known to be associated with systemic immune suppression including those drugs which are prescribed for solid organ or stem cell transplant, autoimmune/inflammatory disorders, or other related medical conditions
  • The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a systemic auto-immune/inflammatory disease or other autoimmune disorder with the exception of: vitiligo, diabetes or thyroid dysfunction
  • The subject is unable to give informed consent
  • The subject is a prisoner
  • The subject is cognitively impaired, and unable to give informed consent
  • The subject is pregnant, as defined by a presumptive sign of pregnancy such as missed menses or a positive pregnancy test
  • The subject requires or is likely to require more than a 2-week course of corticosteroids of > 4 mg
  • Note: The effects of the investigational product on the developing human fetus are unknown; female subjects of childbearing potential are required to have a negative qualitative serum pregnancy test at the time of enrollment and within twenty-four (24) hours prior to the first dose of the investigational product * Female subject of childbearing potential is defined as follows: ** Subject with regular menses ** Subject with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding ** Subject with history of tubal ligation * Female subject not of childbearing potential is defined as follows: ** Subject who has undergone hysterectomy and/or bilateral oophorectomy ** Subject who is post-menopausal, which is defined as amenorrhea for at least one (1) year in a female subject who is greater than forty-five (> 45) years old

Locations & Contacts

New York

New York
Icahn School of Medicine at Mount Sinai
Status: Active
Contact: Adilia Maria Vicente Hormigo
Phone: 212-824-8579
Email: adilia.hormigo@mssm.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the tolerability and safety profile of personalized mutation-derived tumor antigens (MTA)-based vaccine as well the nature and severity of any and all toxicities as determined by the number of patients who experience adverse events, and/or dose-limiting toxicities (DLT) as defined by common criteria developed by the United States National Institutes of Health (NIH), National Cancer Institute and put forward as the Common Terminology Criteria for Adverse Events (NCI-CTCAE 4.0) resulting from the administration of personalized MTA-based vaccine in patients with newly diagnosed glioblastoma (GBM) who are receiving adjuvant treatment with temozolomide chemotherapy. (Phase Ia)

II. To determine the feasibility of personalized MTA-based vaccine, by estimation of the proportion of enrolled subjects in the study that have successful administration of at least one dose of the vaccine. (Phase Ia)

III. To evaluate the tolerability and safety profile of personalized MTA-based vaccine with concurrent tumor treatment fields (TTFields) as well the nature and severity of any and all toxicities as determined by the number of patients who experience adverse events, and/or dose-limiting toxicities (DLT) as defined by common criteria developed by the United States National Institutes of Health (NIH), National Cancer Institute and put forward as the Common Terminology Criteria for Adverse Events (NCI-CTCAE 4.0) resulting from the administration of personalized MTA-based vaccine and TTFields in patients with newly diagnosed GBM who are receiving adjuvant treatment with temozolomide chemotherapy. (Phase Ib)

IV. To further evaluate the feasibility of personalized MTA-based vaccine, by estimation of the proportion of enrolled subjects in the study that have successful administration of at least one dose of the vaccine. (Phase Ib)

SECONDARY OBJECTIVES:

I. To evaluate the immunogenicity of a fully personalized therapeutic vaccine directed towards mutation-derived tumor antigens in patients with newly diagnosed GBM. (Phase Ia)

II. To evaluate the immunogenicity of TTFields and a fully personalized therapeutic vaccine directed towards mutation-derived tumor antigens in patients with newly diagnosed GBM. (Phase Ib)

III. To determine the % progression-free survival at 6 months in patients with newly diagnosed GBM who are treated with personalized MTA-based vaccine and TTFields in combination with temozolomide chemotherapy, by using advanced magnetic resonance imaging (MRI) as the surrogate biomarker. (Phase Ib)

IV. To determine % 1-year and 2-year survival in patients with newly diagnosed GBM treated with TTFields and a fully personalized therapeutic MTA-based vaccine. (Phase Ib)

V. To investigate tissue biomarkers such as PD-1 ligands and PD-1 receptor expression, tumor infiltrating lymphocytes, resident microglia, CD4/CD8, regulatory T cells (Tregs) and tumor molecular signature by using multiplex immunohistochemistry in the surgical specimens of the initial resection and any specimen obtained in patients who require re-resection after the treatment with personalized MTA-based vaccine and TTFields. (Phase Ia and Ib)

VI. To determine MGMT promoter methylation status EGFR amplification, ATRX retention, BRAFv600E mutation, 1p19q status and IDH1 mutation in GBM specimens. (Phase Ia and Ib)

VII. To evaluate circulating cellular signature profiling by mass cytometry (CyTOF) in order to characterize effector and regulatory T cell phenotype, natural killer (NK) and myeloid cell population phenotype. (Phase Ia and Ib)

VIII. To characterize signatures of plasma analytes by multiplex plasma protein analysis of cytokine and chemokine profiles including IFN-alpha, IL-6, IL-1beta, IL-8, IL-12, TNF-alpha, IDO, IL-10, IL-4, IL-2, MIP-1beta and interferon-gamma. (Phase Ia and Ib)

IX. To prospectively determine % 1 and 2-year quality of life of patients treated with NovoTTF-200A together with temozolomide to those treated with temozolomide alone. (Phase Ia and Ib)

OUTLINE:

PHASE IA: Starting between days 10-15 of course 1 of standard of care maintenance temozolomide treatment, patients receive MTA-based vaccine intracutaneously and poly ICLC subcutaneously (SC) on the second day every other week for 4 doses and then once a month for 10 months in the absence of disease progression or unacceptable toxicity.

PHASE IB: Starting between days 10-15 of course 1 of standard of care maintenance temozolomide treatment, patients receive MTA-based vaccine intracutaneously and poly ICLC SC on the second day every other week for 4 doses and then once a month for 10 months. Patients are also treated with NovoTTF-200A device >= 18 hours daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 42 days and then at 2 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Icahn School of Medicine at Mount Sinai

Principal Investigator
Adilia Maria Vicente Hormigo

Trial IDs

Primary ID 17-0566
Secondary IDs NCI-2018-00101
Clinicaltrials.gov ID NCT03223103