GMCI, Nivolumab, and Radiation Therapy in Treating Patients With Newly Diagnosed High-Grade Gliomas
NCT ID: NCT03576612
Last Updated: 2025-02-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1
41 participants
INTERVENTIONAL
2018-02-27
2023-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Gene Mediated Cytotoxic Immunotherapy (GMCI) involves the use of aglatimagene besadenovec (AdV-tk) injection into the tumor site and oral valacyclovir to kill tumor cells and stimulate the immune system. Nivolumab is an immune checkpoint inhibitor that may also stimulate the immune system by blocking the PD-1 immune suppressive pathway. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors and temozolomide is a chemotherapy drug that kills tumor cells. Giving GMCI, nivolumab, radiation therapy, and temozolomide may work better in treating patients with high-grade gliomas
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Nivolumab, BMS-986205, and Radiation Therapy With or Without Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma
NCT04047706
Testing the Use of the Immunotherapy Drugs Ipilimumab and Nivolumab Plus Radiation Therapy Compared to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Unmethylated Glioblastoma
NCT04396860
Phase 1b Study of AdV-tk + Valacyclovir Combined With Radiation Therapy for Malignant Gliomas
NCT00751270
Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade
NCT03493932
Adavosertib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed or Recurrent Glioblastoma
NCT01849146
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. To assess the safety/maximum tolerated dose (MTD) of the combination of aglatimagene besadenovec (AdV-tk) given intra-cranially at the time of initial tumor resection followed by valacyclovir (GMCI), nivolumab, and standard of care (radiation therapy \[RT\]+temozolomide \[TMZ\]) in patients with high-grade gliomas (HGG).
PRIMARY OBJECTIVES:
I. To assess the safety/maximum tolerated dose (MTD) of the combination of aglatimagene besadenovec (AdV-tk) given intra-cranially at the time of initial tumor resection followed by valacyclovir (GMCI), nivolumab, and standard of care (radiation therapy \[RT\]+temozolomide \[TMZ\]) in patients with high-grade gliomas (HGG).
SECONDARY OBJECTIVES:
I. To evaluate safety and toxicity of this combined treatment regimen. II. To estimate overall survival. III. To estimate progression free survival. IV. Immune biomarkers, including serum extracellular vesicles (EVs).
OUTLINE:
Patients undergo tumor resection and receive AdV-tk injection into the wall of the resection cavity. Patients then receive valacyclovir orally three times per day for 14 days. Beginning on approximately day 8, patients undergo radiation therapy five days per week for 6 weeks. Temozolomide will be initiated on approximately day 15 after valacyclovir is completed and will continue until MGMT methylation status is known. If unmethylated, temozolomide will be discontinued: these patients will constitute Cohort 1. In Cohort 2 - patients with methylated MGMT - temozolomide will continue. If methylation status is unable to be determined, those patients will also continue receiving temozolomide (Cohort 2). Both cohorts will receive nivolumab intravenously every two weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months for 2 years, and then every 6 months thereafter.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Cohort 1: MGMT Unmethylated Patients
After confirmation of high grade glioma, AdV-tk injection into wall of resection cavity. Valacyclovir starting 1-3 days post-surgery for 14 days. Radiation begins approximately day 8 and continues for 6 weeks. Temozolomide started after complete valacyclovir and stop when MGMT unmethylated result obtained. Nivolumab every 2 weeks x 26 doses up to 52 weeks. MRI every 8 weeks until progression.
AdV-tk
Given IT
Valacyclovir
Given PO days 1-14; 1-3 days post surgery
Radiation
Undergo RT, 60Gy in 30 daily fractions M-F for 6weeks
Temozolomide
Given PO during RT 75mg/m2 daily during RT Post RT cycle 1: 150mg/m2 days 1-5 150mg/m2 cycle 2-6: days 1-5 (150-200mg/m2)
Nivolumab
day 15 post surgery 240mg IV q2wks x 26 doses , up to 52 weeks
Laboratory Biomarker Analysis
correlative studies
Cohort 2: MGMT Methylated & undetermined Patients
After confirmation of high grade glioma, AdV-tk injection into wall of resection cavity. Valacyclovir starting 1-3 days post-surgery for 14 days. Radiation begins approximately day 8. Temozolomide started after complete valacyclovir and continue during radiation then 5 week break and then begin adjuvant temozolomide dosing. Nivolumab every 2 weeks x 26 doses up to 52 weeks. MRI every 8 weeks until progression.
AdV-tk
Given IT
Valacyclovir
Given PO days 1-14; 1-3 days post surgery
Radiation
Undergo RT, 60Gy in 30 daily fractions M-F for 6weeks
Temozolomide
Given PO during RT 75mg/m2 daily during RT Post RT cycle 1: 150mg/m2 days 1-5 150mg/m2 cycle 2-6: days 1-5 (150-200mg/m2)
Nivolumab
day 15 post surgery 240mg IV q2wks x 26 doses , up to 52 weeks
Laboratory Biomarker Analysis
correlative studies
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
AdV-tk
Given IT
Valacyclovir
Given PO days 1-14; 1-3 days post surgery
Radiation
Undergo RT, 60Gy in 30 daily fractions M-F for 6weeks
Temozolomide
Given PO during RT 75mg/m2 daily during RT Post RT cycle 1: 150mg/m2 days 1-5 150mg/m2 cycle 2-6: days 1-5 (150-200mg/m2)
Nivolumab
day 15 post surgery 240mg IV q2wks x 26 doses , up to 52 weeks
Laboratory Biomarker Analysis
correlative studies
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients must have a Karnofsky performance status \>= 70% (i.e. the patient must be able to care for himself/herself with occasional help from others)
* Absolute neutrophil count \>= 1,500/uL
* Platelets \>= 100,000/uL
* Hemoglobin \>= 9 g/dL
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN), (except for patients with known Gilbert's syndrome who must have normal direct bilirubin)
* Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransaminase (ALT) serum glutamate pyruvate transaminase (SGPT) =\< 3.0 x institutional ULN
* Creatinine =\< institutional ULN
* Calculated creatinine clearance \>= 40 ml/min (use a modified Cockcroft-Gault equation)
* Activated partial thromboplastin time/partial thromboplastin time (APTT/PTT) =\< 1.5 x institutional ULN
* Patients must be able to provide written informed consent
* Patients must have magnetic resonance imaging (MRI) within 14 days of starting treatment; patients must be able to tolerate MRI
* Women of childbearing potential must agree to have a negative serum pregnancy test within 24 hours prior to treatment start; women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and through at least 5 months after the last dose of study drug; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; sexually active men of reproductive potential who are partners of women with reproductive potential must also agree to use adequate contraception prior to the study, for the duration of study participation, and through at least 7 months after the last dose of study drug; adequate methods of effective birth control include sexual abstinence (men, women); vasectomy; or a condom with spermicide (men) in combination with barrier methods, hormonal birth control or intrauterine device (IUD) (women)
* Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for \>= two years; patients with low-risk prostate cancer on active surveillance are eligible
* Patients must be able to swallow oral medications
* Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor infiltrating lymphocyte \[TIL\], lymphokine-activated killer \[LAK\] or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed
Exclusion Criteria
* Patients with a history of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to valacyclovir, acyclovir, or temozolomide are ineligible; the valacyclovir and temozolomide package inserts can be referenced for more information
* Patients with a history of severe hypersensitivity reaction to any monoclonal antibody are ineligible
* Patients who require therapy with systemic immunosuppressive drugs except corticosteroids are ineligible
* Patients with a history of active autoimmune disease requiring treatment in the past 2 years are ineligible
* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active liver disease or active hepatitis, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with these agents through 1 week after receiving the last dose of study drugs
* Patients who are known to be human immunodeficiency virus (HIV) positive are ineligible
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Bristol-Myers Squibb
INDUSTRY
Candel Therapeutics, Inc.
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Patrick Wen, MD
Role: STUDY_CHAIR
Dana Farber
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Henry Ford Hospital
Detroit, Michigan, United States
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States
Abrams Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Wen PY, Manzanera A, Duault C, Gonzalez-Kozlova E, Lopez L, Grossman SA, Ye X, Fisher J, Lee I, Walbert T, Snyder J, Brem S, Desai A, Bagley SJ, Kakani C, Strowd R, Tatter S, Laxton A, Lesser G, Amankulor N, Lieberman F, Drappatz J, Mantica M, Triggs D, Haymaker C, Wistuba II, Al-Atrash G, Mendoza Perez J, Futreal A, Little LD, Islam MDH, Duose D, Jiang P, Reuben A, Lawler SE, Pichavant M, Gentles A, Bendall S, Kong A, Camacho C, Del Valle D, Kim-Schulze S, Gnjatic S, Sharon E, Nowicki MO, Peruzzi P, Lane D, Aguilar-Cordova E, Aguilar LK, Nichols G, Dwyer J, Tak PP, Maecker H, Barone F, Chiocca EA. A multi-institutional phase 1 clinical trial exploring upfront multimodal standard of care and combined immunotherapies for newly diagnosed glioblastoma. Neuro Oncol. 2025 Mar 22:noaf079. doi: 10.1093/neuonc/noaf079. Online ahead of print.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
IRB00172749
Identifier Type: OTHER
Identifier Source: secondary_id
ABTC-1603
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.