VB-111 in Surgically Accessible Recurrent/Progressive GBM

  • STATUS
    Recruiting
  • End date
    Aug 1, 2024
  • participants needed
    45
  • sponsor
    Dana-Farber Cancer Institute
Updated on 15 June 2022
cancer
corticosteroids
nitrosoureas
serum pregnancy test
measurable disease
direct bilirubin
bilateral oophorectomy
MRI
dexamethasone
neutrophil count
bevacizumab
glioblastoma multiforme
temozolomide
gliosarcoma
malignant glioma
brain tumor
tumor progression
estradiol
vascular endothelial growth factor
renal function test
investigational agent
formalin-fixed paraffin-embedded
tumor treating fields therapy
stereotactic biopsy

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.

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.

Details
Condition Glioblastoma, Recurrent Glioblastoma
Treatment Placebo, bevacizumab, Surgery, VB11
Clinical Study IdentifierNCT04406272
SponsorDana-Farber Cancer Institute
Last Modified on15 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma)
° ± µ ™ ®
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
Surgically resectable disease at progression
The maximal tumor volume at baseline meets the following criteria as determined by a local site investigator or surgeon: Longest diameter ≤ 4CM
An interval of the following durations prior to randomization
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
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
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
Adequate bone marrow, liver, and renal function according to the following criteria
Age ≥ 18 years on day of signing informed consent
KPS ≥ 70% (see Appendix A)
Absolute neutrophil count ≥ 1,500 cells/mL ~ 1.5 K/μL
Ability to understand and willingness to sign a written informed consent document
Platelets ≥ 100,000 cells/mL ~ 100 K/μL
Availability of 10 unstained formalin-fixed paraffin-embedded slides
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
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
Serum creatinine level ≤ ULN or creatinine clearance ≥ 50 mL/min for participants with creatinine levels above normal limits (calculated by the Cockcroft-Gault formula)
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
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
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
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

Exclusion Criteria

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
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 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
History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red blood per episode) within 6 months of randomization
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