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GlioblastomaPhase 2NCT04406272

VB-111 in Surgically Accessible Recurrent/Progressive GBM

A Phase 2 study testing VB11, Surgery and Bevacizumab in people with Glioblastoma and Recurrent Glioblastoma, run by Dana-Farber Cancer Institute at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This research study is studying a new viral cancer therapy, ofranergene obadenovec (VB-111), for recurrent or progressive glioblastoma (GBM), a brain tumor that is growing or progressing despite earlier treatment. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma, Recurrent Glioblastoma
What is being tested?
VB11, Surgery and Bevacizumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
15 participants
Where
4 sitesUnited States
Study dates
1 Aug 2020to 1 Aug 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma).
  • First or second progression of glioblastoma/gliosarcoma (according to RANO criteria) following standard of care treatment upon initial diagnosis with radiation.
  • Measurable disease by RANO criteria at progression.
  • The maximal tumor volume at baseline meets the following criteria as determined by a local site investigator or surgeon: Longest diameter ≤ 4CM.
  • Surgically resectable disease at progression.
  • An interval of the following durations prior to randomization:
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  • At least 28 days from prior surgical resection, or 7 days from stereotactic biopsy
  • At least 12 weeks from prior radiotherapy, unless there is unequivocal histologic confirmation of tumor progression
  • At least 23 days from prior chemotherapy
  • At least 42 days from nitrosureas
  • At least 42 days from other anti-tumor therapies (including vaccines)
  • At least 28 days from any investigational agent NOTE: no wash-out period required from TTF.
  • Participants must have recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy (including but not limited to exceptions of alopecia, laboratory values listed per inclusion criteria, and lymphopenia which is common after therapy with temozolomide.
  • Corticosteroid use at or less than dexamethasone 2mg daily. Participants should be on a stable or decreasing dose for at least 7 days prior to randomization.
  • Age ≥ 18 years on day of signing informed consent
  • KPS ≥ 70% (see Appendix A)
  • Adequate bone marrow, liver, and renal function according to the following criteria:
  • Absolute neutrophil count ≥ 1,500 cells/mL ~ 1.5 K/μL
  • Platelets ≥ 100,000 cells/mL ~ 100 K/μL
  • Total bilirubin ≤ 1.5 X institutional ULN OR Direct bilirubin ≤ institutional ULN for subjects with total bilirubin levels > 1.5 institutional ULN
  • Aspartate aminotransferase (AST) ≤ 2.0 x ULN
  • Serum creatinine level ≤ ULN or creatinine clearance ≥ 50 mL/min for participants with creatinine levels above normal limits (calculated by the Cockcroft-Gault formula)
  • Ability to understand and willingness to sign a written informed consent document
  • Availability of 10 unstained formalin-fixed paraffin-embedded slides.
  • MRI within 14 days prior to registration.
  • NOTE: Due to the fact that the screening MRI will not be used for response purpose, participants may be registered if screening CT or MRI is > 14 days of registration if prospective approval is received from Overall PI
  • Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin urine or serum pregnancy test within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • NOTE: Women are considered postmenopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or have had surgical bilateral oophorectomy (withor without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment if she is considered not of child bearing potential.
  • Males and females of childbearing potential must utilize a standard contraception method throughout the trial and up to 120 days after the last dose of treatment on study.
  • NOTE: Women of childbearing potential and men with female spouses of childbearing potential must agree to use two methods of reliable contraception simultaneously or to practice complete abstinence from heterosexual contact prior to study entry, while receiving treatment, and for 4 months after undergoing treatment. One method must include a highly effective method such as an intrauterine device, hormonal (birth control pills, injections or implants), tubal ligation or partner's vasectomy. The other method can be an additional hormonal therapy or barrier method such as a male condom, diaphragm or cervical cap. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately

Who cannot join

  • Current or planned participation in a study of an investigational agent or using an investigational device.
  • Has tumor primarily localized to the brainstem or spinal cord
  • Has presence of diffuse leptomeningeal disease or extracranial disease.
  • Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to first study treatment
  • Minor surgical procedure (e.g. stereotactic biopsy or shunt placement) within 7 days of first study treatment, placement of vascular access within 2 days of first study treatment
  • Expected to have surgery other than the neurosurgical procedure intended for the GBM lesion during study treatment period
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  • Prior stereotactic radiotherapy (Note: those who have had biopsy proven tumor recurrence at a site of SRS treatment should be considered eligible if approved by the study central Investigator)
  • Prior anti-angiogenic therapy including VEGF sequestering agents (i.e. bevacizumab, aflibercept, etc.) or VEGFR inhibitors (cedirinib, pazopanib, sunitinib, sorafenib, etc.)
  • Prior administration of the study drug VB-111
  • Concomitant medication that may interfere with study results (e.g. immunosuppressive agents other than inhaled, topical or intra-articular steroids or a stable or decreasing dose of oral corticosteroids of up to <2 mg/day dexamethasone equivalent)
  • Known active second malignancy. Exceptions include non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Participants are not considered to have currently active malignancy if they have completed anticancer therapy and have been disease free for greater than 2 years prior to screening
  • Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • History of stroke or transient ischemic attack within 6 months prior to randomization
  • Evidence of CNS hemorrhage CTCAE grade 2 or above on screening MRI
  • Active cardiac disease within 6 months prior to randomization (i.e. acute coronary syndrome, unstable angina, New York Heart Association grade II or greater congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment)
  • Significant vascular disease within 6 months prior to randomization (e.g. aortic aneurysm requiring surgical repair, peripheral arterial thrombosis, symptomatic peripheral vascular disease)
  • History of venous thromboembolism CTCAE version 5.0 grade 3 or greater
  • Known proliferative and/or vascular retinopathy
  • Inadequately controlled hypertension (defined as systolic blood pressure > 150mmHg and/or diastolic blood pressure > 100mmHg) within 1 week of randomization
  • History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red blood per episode) within 6 months of randomization.
  • History of active gastrointestinal bleeding within 6 months prior to randomization.
  • History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation)
  • Current or recent (within 10 days of study randomization) use of aspirin > 325mg/day, clopidogrel > 75mg/day or equivalent. Therapeutic or prophylactic use of anticoagulants is allowed
  • Known liver disease (alcoholic, drug/toxin induced, genetic or autoimmune)
  • History of gastrointestinal perforation or abscess
  • Positive testing to any of the following viruses: HIV, HBV, HCV within the last 6 months. Exceptions include participants with serology positive for HBV indicating past exposure but without evidence of active infection (e.g. negative PCR)
  • History of intracranial abscess within 6 months prior to randomization
  • Serious non-healing wound, active ulcer, or untreated bone fracture
  • Pregnant or breastfeeding participants

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of California, Los Angeles (UCLA)

    Los Angeles, California, 90095

  • Huntsman Cancer Institute (HCI), University of Utah

    Salt Lake City, Utah, 84112

  • UT Health San Antonio MD Anderson Cancer Center (Mays Cancer Center)

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A Randomized, Controlled Phase II Surgical Trial to Evaluate Early Immunologic Pharmacodynamic Parameters for the Viral Cancer Therapy Ofranergene Obadenovec (VB-111) in Patients With Surgically Accessible Recurrent/Progressive Glioblastoma

This research study is studying a new viral cancer therapy, ofranergene obadenovec (VB-111), for recurrent or progressive glioblastoma (GBM), a brain tumor that is growing or progressing despite earlier treatment.

Read the detailed description

This is a randomized, controlled, blinded, phase II, surgical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether it works in treating a specific disease. "Investigational" means that the drug is being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved this intervention for recurrent or progressive glioblastoma.

In this research study, ofranergene obadenovec (VB-111) is the investigational drug being studied. VB-111 has been studied in lab experiments and in other types of cancer, and information from these studies suggest that it may be beneficial for recurrent or progressive glioblastoma.

VB-111 works by targeting and damaging the blood vessels that grow and nourish cancerous tumors leading to tumor starvation.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. After enrollment, participants will be randomized into one of three study groups. Randomization means that participants are put into a group by chance. Neither the participant nor the research doctor will choose what group a participant will be in.

  • In group A participants receive VB-111 before and after surgery.
  • In group B participants receive VB-111 after surgery.
  • In group C participants won't receive VB-111 but would receive standard of care.

Treatment will be provided blindly, meaning participants do not know (are blinded as to) what treatment they are receiving to ensure that the results are not affected by a placebo effect (the power of suggestion). Participants will be given a study medication and it will contain either VB-111 or placebo (IV solution with no medicine).

VBL Therapeutics is supporting this research study by providing funding for the research study and the study drug.

Participants will be in this research study for as long as they do not have serious side effects and their disease does not get worse. It is expected that about 45 people will take part in this research study.

Being tested
VB11, Surgery, Placebo, Bevacizumab
Keywords
Glioblastoma, Recurrent Glioblastoma
Medical subject headings
Glioblastoma

What participants receive

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

  • VB11Drug

    Also called Ofranergene obadenovec

    Intravenously administered type of gene therapy that works by blocking the process of blood-vessel creation. Disrupting a cancer from growing blood vessels, might slow the growth of the cancer or shrink it.

  • SurgeryProcedure or surgery

    Treatment of disease or injury by cutting, abrading, suturing, or otherwise physically changing body tissues and organs.

  • PlaceboOther

    Intravenous solution that has no therapeutic effect, used as a control in testing investigational drug.

  • BevacizumabDrug

    Also called Avastin

    A type of antibody, Bevacizumab is intravenously administered and works by binding to and disrupting the vascular endothelial growth factor (VEGF). VEGF is a signal protein produced by cells that stimulates the formation of blood vessels. By disrupting VEGF, Bevacizumab helps to prevent the growth and maintenance of tumor blood vessels.

Study groups in NCT04406272
Study groupRoleWhat they receive
Before and After SurgeryExperimentalVB-111 will be administered intravenously at a pre-determined dose at 14-28 days prior to surgery. Upon recovering from surgery (within 28-35 days after surgery), participants will receive intravenous VB-111 every 6 weeks. Participants evidencing disease progression may initiate bevacizumab at a pre-determined dose as needed for supportive care and will continue with VB-111 infusions every 6 weeks until tumor growth is evidenced a two consecutive time points.
Receives: Drug: VB11; Procedure: Surgery; Drug: Bevacizumab
After SurgeryExperimentalPlacebo (IV solution with no medicine) will be administered intravenously at a pre-determined dose at 14-28 days prior to surgery. Upon recovering from surgery (within 28-35 days after surgery), participants will receive intravenous VB-111 every 6 weeks. Participants evidencing disease progression may initiate bevacizumab at a pre-determined dose as needed for supportive care and will continue with VB-111 infusions every 6 weeks until tumor growth is evidenced a two consecutive time points.
Receives: Drug: VB11; Procedure: Surgery; Other: Placebo; Drug: Bevacizumab
After Surgery Standard of CareExperimentalPlacebo (IV solution with no medicine) will be administered intravenously at a pre-determined dose at 14-28 days prior to surgery. Upon recovery from surgery, participants will receive standard of care treatment every 6 weeks until tumor growth is evidenced a two consecutive time points.
Receives: Procedure: Surgery; Other: Placebo

What is being measured

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

  1. Tumor Infiltrating T Cell (TIL) Density

    TIL Density Analysis was not - and will not be - performed on study samples, therefore no data was generated for this study objective.

    • Tumor infiltrating T cell (TIL) density is defined as the number of T lymphocytes per nucleated cell, and calculated by detailed sequencing of recombined T cell receptor sequences obtained from the tumor specimen gDNA.
    • Plan had been to use a two-sample t-test with tumor size stratification to test the difference of tumor infiltrating T cell density between the two groups (Group A vs combined Group B+C).

    Measured: 2 years

  2. # of Participants to Experience a Reportable SAE on Study

    AEs graded using CTCAE version 5.0 criteria. Safety will be assessed by quantifying the toxicities and grades experienced by participants who have received VB-111, including serious adverse events (SAEs) All participants who receive at least one dose of VB-111/placebo will be evaluable for toxicity from the time of their first treatment.

    Measured: 2 years

Secondary outcomes (2)

  1. 6-month Progression-free Survival (PFS-6)

    Defined as the %age of participants with progression-free survival at 6 months from surgery as defined by RANO. Recurrent/progressive GBM participants treated with VB-111 (Group A and Group B) compared to control (Group C), using RANO criteria. Progression is defined using Radiologic Assessment in Neuro-Oncology (RANO) criteria, as any of the following:

    • ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement, on stable or increasing doses of corticosteroids
    • Any new lesion
    • Significant increase in T2/FLAIR non-enhancing lesions on stable or increasing doses of corticosteroids not felt to be caused by co-morbid events
    • Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose
    • Clear progression of non-measurable disease
    • Or failure to return for evaluation due to death or deteriorating condition

    Measured: 6 months

  2. Overall Survival (OS)

    OS, analyses will be conducted using historical comparison data which are available from a pooled analysis of Phase II experience in recurrent Grade IV gliomas who have undergone surgery either just prior to starting treatment or as part of. Kaplan-Meier (KM) curves and median estimates from the KM curves will be provided as appropriate. Participants without efficacy evaluation data or without survival data will be censored at Day 1. For evaluation of the expansion of TCR clones, a two-sample T-test with Bonferroni adjustment will be used to compare the increase number of expanded TCR clones after VB-111 in Group A+B vs Group C.

    Measured: Time from randomization until death from any cause; 37 months was the maximum time a participant remained in follow-up before passing away (10 pts), withdrawing consent (2 pts), being lost to follow-up (2 pts), or trial termination (1 pt).

Timeline

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

  1. First posted28 May 2020
  2. Study start1 Aug 2020
  3. Primary completion1 Aug 2024
  4. Study completion1 Aug 2024

Why it stopped: Trial stopped at request of VBL Therapeutics, as they are no longer pursuing their VB-111 development program.

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04406272
Sponsor's protocol ID
19-792
Status last verified
May 2025
First submitted
15 May 2020
Last updated
10 Jun 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VB11, Surgery and Bevacizumab in people with Glioblastoma and Recurrent Glioblastoma, run by Dana-Farber Cancer Institute at 4 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 30 inclusion and 29 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: stopped early, as of the sponsor's last update on 10 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Tumor Infiltrating T Cell (TIL) Density (time frame: 2 years). The study lists 2 primary outcomes in all. 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 NCT04406272.

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 10 Jun 2025.

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