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Glioma, MalignantPhase 1GMCINCT03576612

GMCI, Nivolumab, and Radiation Therapy in Treating Patients With Newly Diagnosed High-Grade Gliomas

A Phase 1 study testing AdV-tk, Valacyclovir and Radiation in people with Glioma, Malignant, run by Candel Therapeutics, Inc. at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this phase I trial is to test the safety of combining GMCI, an immunostimulator, plus nivolumab, an immune checkpoint inhibitor (ICI), with standard of care radiation therapy, and temozolomide in treating patients with newly diagnosed high-grade gliomas. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioma, Malignant
What is being tested?
AdV-tk, Valacyclovir and Radiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
5 sitesUnited States
Study dates
27 Feb 2018to 30 Jun 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have operable brain tumor presumed to be high grade glioma (HGG) based on clinical and radiologic evaluation, where a gross total surgical resection of the contrast-enhancing area is intended; pathologic confirmation of HGG must be made at the time of surgery prior to AdV-tk injection, if not previously determined
  • 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)
Show all 16Show fewer
  • 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

Who cannot join

  • Patients receiving any other investigational agents are ineligible
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Abrams Cancer Center of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Hillman Cancer Center at University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15232

  • Wake Forest University Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: Phase I Study of Neoadjuvant GMCI Plus Immune Checkpoint Inhibitor Combined With Standard of Care for Newly Diagnosed High-Grade Gliomas

The purpose of this phase I trial is to test the safety of combining GMCI, an immunostimulator, plus nivolumab, an immune checkpoint inhibitor (ICI), with standard of care radiation therapy, and temozolomide in treating patients with newly diagnosed high-grade gliomas.

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
AdV-tk, Valacyclovir, Radiation, Temozolomide, Nivolumab
Keywords
glioblastoma, newly diagnosed, GMCI, Checkpoint inhibitor
Medical subject headings
Glioma, Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AdV-tkBiological

    Also called Aglatimagene Besadenovec

    Given IT

  • ValacyclovirDrug

    Also called 124832-26-4, L-Valine ester with 9-((2-hydroxyethoxy)methyl)guanine, Zelitrex

    Given PO days 1-14; 1-3 days post surgery

  • RadiationRadiation

    Also called Irradiate, irradiation, radiotherapy, RT

    Undergo RT, 60Gy in 30 daily fractions M-F for 6weeks

  • TemozolomideDrug

    Also called TMZ

    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)

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    day 15 post surgery 240mg IV q2wks x 26 doses , up to 52 weeks

  • Laboratory Biomarker AnalysisOther

    correlative studies

Study groups in NCT03576612
Study groupRoleWhat they receive
Cohort 1: MGMT Unmethylated PatientsExperimentalAfter 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.
Receives: Biological: AdV-tk; Drug: Valacyclovir; Radiation: Radiation; Drug: Temozolomide; Biological: Nivolumab; Other: Laboratory Biomarker Analysis
Cohort 2: MGMT Methylated & undetermined PatientsExperimentalAfter 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.
Receives: Biological: AdV-tk; Drug: Valacyclovir; Radiation: Radiation; Drug: Temozolomide; Biological: Nivolumab; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

    National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 will be used for scoring toxicity and adverse events. The severity and frequency of toxicity will be tabulated by the tested dose or doses using descriptive statistics. The proportions of subjects who experienced grade 3 or above toxicities will be estimated, along with 95% confidence intervals by each type of toxicity.

    Measured: Up to 2 years

Secondary outcomes (7)

  1. Overall survival (death)

    To estimate overall survival - endpoint is death. Median time of survival along with 95% confidence interval will be estimated using the Kaplan-Meier method.

    Measured: From initial diagnosis to the date of death/or censored at the time of last known alive, assessed for up to 2 years

  2. Progression-free survival (progression)

    To estimate progression-free survival - endpoint is progression. Median time of progression-free survival along with 95% confidence interval will be estimated using Kaplan-Meier method.

    Measured: From initial diagnosis to the date progression is defined, assessed for up to 2 years

  3. Immune profiling - Tumor Tissue

    Tumor profiling by immunohistochemistry and Nanostring at baseline and when samples available after treatment.

    Measured: Up to 2 years

  4. Tumor mutation - Tumor Tissue

    Mutational profiling by sequence or transcriptome analysis from tumor tissue

    Measured: Up to 2 years

  5. Peripheral blood mononuclear cells (PBMCs) in serum samples

    Standard descriptive statistics will be used to summarize proportion of PBMCs.

    Measured: Up to 2 years

  6. Immune characterization as determined by Cytokines

    Immune characterization of surface and content proteins is determined by presence of cytokines in serum.

    Measured: Up to 2 years

  7. Immune characterization as determined by Extracellular vesicles (EVs) proteins

    Immune characterization of surface and content proteins based on presence of extracellular vesicles in serum samples.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jul 2018
  2. Study start27 Feb 2018
  3. Primary completion30 Jun 2023
  4. Study completion30 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Model description
Newly diagnosed HGG: surgically eligible patients AdV-tk into wall of resection cavity; 1-3 days post-surgery Valacyclovir d1-14; Day 8 RT for 6 wks; day 15 TMZ 75mg/m2 daily; Nivo 240mgIV every 2 weeks
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03576612
Sponsor's protocol ID
ABTC-1603
Other IDs
IRB00172749, UM1CA137443
Acronym
GMCI
Status last verified
Feb 2025
First submitted
24 May 2018
Last updated
14 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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 Oct 1;27(10):2617-2631. doi: 10.1093/neuonc/noaf079.

    PubMed 40120123

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AdV-tk, Valacyclovir and Radiation in people with Glioma, Malignant, run by Candel Therapeutics, Inc. at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03576612, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2025.

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