Brief Summary
The purpose of this study is to use precision medicine in the form of a vaccine, a mutation-derived tumor antigen vaccine (MTA-based vaccine) in combination with standard care treatment of glioblastoma (GBM) and Tumor Treating Fields (TTFields).
The study is designed to determine whether this treatment combination is well tolerated and safe.
The study is designed to determine whether this treatment combination is well tolerated and safe.
Brief Title
Safety and Immunogenicity of Personalized Genomic Vaccine and Tumor Treating Fields (TTFields) to Treat Glioblastoma
Detailed Description
This is a single-arm, single institution phase 1a / 1b study to test the safety, tolerability, and immunogenicity of MTA-based personalized vaccine in patients with newly diagnosed GBM along with the use of continual TTFields. MTA-based personalized vaccine is prepared in the laboratory with several peptides based on each patient's own tumor sequence.
The vaccine is given after the radiation and chemotherapy portion of the treatment, in the maintenance phase of temozolomide in conjunction with the TTFields.
The vaccine is given after the radiation and chemotherapy portion of the treatment, in the maintenance phase of temozolomide in conjunction with the TTFields.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Glioblastoma
Eligibility Criteria
Inclusion Criteria:
* Age ≥ 18
* Histological confirmation of GBM (WHO grade IV).
* Stable disease after treatment of radiation with concurrent chemotherapy. If the disease is not stable or progresses while in the study the patient is allowed to continue the study receiving the vaccine if the tumor gets controlled by other modality treatment(s)
* Must have received maximal debulking surgery and undergo radiotherapy concomitant with Temozolomide (45-70Gy)
* Life expectancy \> 16 weeks
* Performance status of 0-2 as determined by Eastern Cooperative Oncology Group (ECOG) and/or Karnofsky Performance Status (KPS) 70-100
* First vaccine treatment start date at least 4 weeks out but not more than 8 weeks from the last dose of concomitant Temozolomide or radiotherapy
* Must have archival tumor tissue that is sufficient quantity and quality for sequencing
* Have adequate bone marrow function
* Requires Dexamethasone ≤ 4mg daily on a stable dose
* Acceptable hematologic, hepatic, and renal function and these tests must be performed within 14 days prior to study
* Must be deemed competent to give informed consent
* 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 participation in the study
Exclusion Criteria:
* Progression of disease at time of screening
* Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias
* Infra-tentorial tumor or multifocal disease
* History of hypersensitivity reaction to Temozolomide or a history of hypersensitivity to Decarbazine (DTIC)
* 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
* Active cancer at the time of screening
* Prior history of unrelated neoplastic disease, and having received systemic therapy for the secondary malignancy within the twelve (12) month period preceding the screening evaluation.
* 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
* 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
* 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
* Less than 18 years of age, or otherwise unable to give informed consent due to minor status
* Prisoner, as defined by \[45 CFR 46.303(c)\]
* Cognitively impaired, and unable to give informed consent
* Pregnant, as defined by a presumptive sign of pregnancy such as missed menses or a positive pregnancy test \[45 CFR 46.203(b)\]
* Requires or is likely to require more than a 2-week course of corticosteroids of \>4mg
* Age ≥ 18
* Histological confirmation of GBM (WHO grade IV).
* Stable disease after treatment of radiation with concurrent chemotherapy. If the disease is not stable or progresses while in the study the patient is allowed to continue the study receiving the vaccine if the tumor gets controlled by other modality treatment(s)
* Must have received maximal debulking surgery and undergo radiotherapy concomitant with Temozolomide (45-70Gy)
* Life expectancy \> 16 weeks
* Performance status of 0-2 as determined by Eastern Cooperative Oncology Group (ECOG) and/or Karnofsky Performance Status (KPS) 70-100
* First vaccine treatment start date at least 4 weeks out but not more than 8 weeks from the last dose of concomitant Temozolomide or radiotherapy
* Must have archival tumor tissue that is sufficient quantity and quality for sequencing
* Have adequate bone marrow function
* Requires Dexamethasone ≤ 4mg daily on a stable dose
* Acceptable hematologic, hepatic, and renal function and these tests must be performed within 14 days prior to study
* Must be deemed competent to give informed consent
* 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 participation in the study
Exclusion Criteria:
* Progression of disease at time of screening
* Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias
* Infra-tentorial tumor or multifocal disease
* History of hypersensitivity reaction to Temozolomide or a history of hypersensitivity to Decarbazine (DTIC)
* 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
* Active cancer at the time of screening
* Prior history of unrelated neoplastic disease, and having received systemic therapy for the secondary malignancy within the twelve (12) month period preceding the screening evaluation.
* 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
* 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
* 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
* Less than 18 years of age, or otherwise unable to give informed consent due to minor status
* Prisoner, as defined by \[45 CFR 46.303(c)\]
* Cognitively impaired, and unable to give informed consent
* Pregnant, as defined by a presumptive sign of pregnancy such as missed menses or a positive pregnancy test \[45 CFR 46.203(b)\]
* Requires or is likely to require more than a 2-week course of corticosteroids of \>4mg
Inclusion Criteria
Inclusion Criteria:
* Age ≥ 18
* Histological confirmation of GBM (WHO grade IV).
* Stable disease after treatment of radiation with concurrent chemotherapy. If the disease is not stable or progresses while in the study the patient is allowed to continue the study receiving the vaccine if the tumor gets controlled by other modality treatment(s)
* Must have received maximal debulking surgery and undergo radiotherapy concomitant with Temozolomide (45-70Gy)
* Life expectancy \> 16 weeks
* Performance status of 0-2 as determined by Eastern Cooperative Oncology Group (ECOG) and/or Karnofsky Performance Status (KPS) 70-100
* First vaccine treatment start date at least 4 weeks out but not more than 8 weeks from the last dose of concomitant Temozolomide or radiotherapy
* Must have archival tumor tissue that is sufficient quantity and quality for sequencing
* Have adequate bone marrow function
* Requires Dexamethasone ≤ 4mg daily on a stable dose
* Acceptable hematologic, hepatic, and renal function and these tests must be performed within 14 days prior to study
* Must be deemed competent to give informed consent
* 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 participation in the study
* Age ≥ 18
* Histological confirmation of GBM (WHO grade IV).
* Stable disease after treatment of radiation with concurrent chemotherapy. If the disease is not stable or progresses while in the study the patient is allowed to continue the study receiving the vaccine if the tumor gets controlled by other modality treatment(s)
* Must have received maximal debulking surgery and undergo radiotherapy concomitant with Temozolomide (45-70Gy)
* Life expectancy \> 16 weeks
* Performance status of 0-2 as determined by Eastern Cooperative Oncology Group (ECOG) and/or Karnofsky Performance Status (KPS) 70-100
* First vaccine treatment start date at least 4 weeks out but not more than 8 weeks from the last dose of concomitant Temozolomide or radiotherapy
* Must have archival tumor tissue that is sufficient quantity and quality for sequencing
* Have adequate bone marrow function
* Requires Dexamethasone ≤ 4mg daily on a stable dose
* Acceptable hematologic, hepatic, and renal function and these tests must be performed within 14 days prior to study
* Must be deemed competent to give informed consent
* 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 participation in the study
Gender
All
Gender Based
false
Keywords
Brain cancer
Glioblastoma
Personalized vaccine
Polyinosinic-polycytidylic acid (Poly-ICLC)
Immunotherapy
Cancer
NovoTTF-200A
Optune
GBM
immunogenicity
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03223103
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2022-13817
Overall Status
Active, not recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Phase I Study of Tumor Treatment Fields and a Personalized Mutation-derived Tumor Vaccine in Patients With Newly Diagnosed Glioblastoma (GCO 17-0566)
Primary Outcomes
Outcome Description
Safety and Tolerability of the personalized treatment regimen will be assessed in tandem using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. NCI-CTCAE is a standard system for grading and reporting adverse events (AEs) in cancer clinical trials to document the occurrence and severity of AEs, with grades ranging from 1 (mild) to 5 (death). DLTs will be summarized and reported.
Outcome Measure
Dose-limiting toxicities (DLT)
Outcome Time Frame
long term, up to 10 years after treatment initiation
Outcome Description
Feasibility of the personalized MTA vaccine will be defined as the successful administration of at least one (1) dose to subjects following tissue sample acquisition and will be expressed as the proportion or percentage subjects enrolled in the study who have successfully been administered at least one dose of the personalized MTA vaccine.
Outcome Measure
Feasibility of Personalized MTA vaccine administration
Outcome Time Frame
Up to 42 weeks after treatment initiation
Secondary Ids
Secondary Id
16-089
Secondary Outcomes
Outcome Description
PFS will be determined by the percentage of patients whose disease remains stable, without disease progression or death, from the time diagnosis until 6 months after diagnosis.
Outcome Time Frame
6 months after diagnosis
Outcome Measure
Progression Free Survival (PFS)
Outcome Description
Overall Survival will be determined by from the time of diagnosis to the time of death, or up to 10 years. OS will be summarized as the percentage of patients who reach the 1-year, 2-year, 5-year, and 10-year milestones.
Outcome Time Frame
1 year, 2 years, 5 years, and 10 years after diagnosis
Outcome Measure
Overall Survival (OS)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Adilia Hormigo
Investigator Email
adilia.hormigo@einsteinmed.edu
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Brain, Spine & Nerve Cancers --- BRAIN NEOPLASMS
Cancer --- NEOPLASMS
Endocrine System Cancers --- NEOPLASMS
Gastrointestinal (GI) Cancers --- NEOPLASMS
Gynecologic Cancers --- NEOPLASMS
Lung & Chest Cancers --- NEOPLASMS
Prostate Cancer --- NEOPLASMS
Skin Cancer --- NEUROECTODERMAL TUMORS
Blood & Bone Marrow Cancers --- NEOPLASMS BY HISTOLOGIC TYPE
Lung & Chest Cancers --- NEOPLASMS, GLANDULAR AND EPITHELIAL
Brain, Spine & Nerve Cancers --- CENTRAL NERVOUS SYSTEM NEOPLASMS
Brain, Spine & Nerve Cancers --- NERVOUS SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Prostate Cancer --- NEOPLASMS BY SITE
Alzheimer's --- BRAIN DISEASES
Brain, Spinal Cord & Nervous System --- BRAIN DISEASES
Brain, Spine & Nerve Cancers --- BRAIN DISEASES
Alzheimer's --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- NERVOUS SYSTEM DISEASES
MeSH Terms
GLIOBLASTOMA
BRAIN NEOPLASMS
NEOPLASMS
ASTROCYTOMA
GLIOMA
NEOPLASMS, NEUROEPITHELIAL
NEUROECTODERMAL TUMORS
NEOPLASMS, GERM CELL AND EMBRYONAL
NEOPLASMS BY HISTOLOGIC TYPE
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
POLY ICLC
PEPTIDES
AMINO ACIDS, PEPTIDES, AND PROTEINS