VB-111 in Surgically Accessible Recurrent/Progressive GBM

Phase 2

Terminated

• Conditions: Glioblastoma; Recurrent Glioblastoma

• Registration Number: NCT04406272
• Lead Sponsor: Dana-Farber Cancer Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-5-15
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Terminated
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria: ° ± µ ™ ®<br><br> - Histologically confirmed World Health Organization Grade IV malignant glioma<br> (glioblastoma or gliosarcoma).<br><br> - First or second progression of glioblastoma/gliosarcoma (according to RANO criteria)<br> following standard of care treatment upon initial diagnosis with radiation.<br><br> - Measurable disease by RANO criteria at progression.<br><br> - The maximal tumor volume at baseline meets the following criteria as determined by a<br> local site investigator or surgeon: Longest diameter = 4CM.<br><br> - Surgically resectable disease at progression.<br><br> - An interval of the following durations prior to randomization:<br><br> - At least 28 days from prior surgical resection, or 7 days from stereotactic<br> biopsy<br><br> - At least 12 weeks from prior radiotherapy, unless there is unequivocal<br> histologic confirmation of tumor progression<br><br> - At least 23 days from prior chemotherapy<br><br> - At least 42 days from nitrosureas<br><br> - At least 42 days from other anti-tumor therapies (including vaccines)<br><br> - At least 28 days from any investigational agent NOTE: no wash-out period<br> required from TTF.<br><br> - Participants must have recovered to grade 0 or 1 or pre-treatment baseline from<br> clinically significant toxic effects of prior therapy (including but not limited to<br> exceptions of alopecia, laboratory values listed per inclusion criteria, and<br> lymphopenia which is common after therapy with temozolomide.<br><br> - Corticosteroid use at or less than dexamethasone 2mg daily. Participants should be<br> on a stable or decreasing dose for at least 7 days prior to randomization.<br><br> - Age = 18 years on day of signing informed consent<br><br> - KPS = 70% (see Appendix A)<br><br> - Adequate bone marrow, liver, and renal function according to the following criteria:<br><br> - Absolute neutrophil count = 1,500 cells/mL ~ 1.5 K/µL<br><br> - Platelets = 100,000 cells/mL ~ 100 K/µL<br><br> - Total bilirubin = 1.5 X institutional ULN OR Direct bilirubin = institutional<br> ULN for subjects with total bilirubin levels > 1.5 institutional ULN<br><br> - Aspartate aminotransferase (AST) = 2.0 x ULN<br><br> - Serum creatinine level = ULN or creatinine clearance = 50 mL/min for<br> participants with creatinine levels above normal limits (calculated by the<br> Cockcroft-Gault formula)<br><br> - Ability to understand and willingness to sign a written informed consent document<br><br> - Availability of 10 unstained formalin-fixed paraffin-embedded slides.<br><br> - MRI within 14 days prior to registration.<br><br> - NOTE: Due to the fact that the screening MRI will not be used for response<br> purpose, participants may be registered if screening CT or MRI is > 14 days of<br> registration if prospective approval is received from Overall PI<br><br> - Women of childbearing potential must have a negative serum beta-human chorionic<br> gonadotropin urine or serum pregnancy test within 72 hours prior to registration. If<br> the urine test is positive or cannot be confirmed as negative, a serum pregnancy<br> test will be required.<br><br> - NOTE: Women are considered postmenopausal and not of child bearing potential if<br> they have had 12 months of natural (spontaneous) amenorrhea with an appropriate<br> clinical profile (e.g., age appropriate, history of vasomotor symptoms) or six<br> months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and<br> estradiol < 20 pg/mL or have had surgical bilateral oophorectomy (withor<br> without hysterectomy) at least six weeks ago. In the case of oophorectomy<br> alone, only when the reproductive status of the woman has been confirmed by<br> follow up hormone level assessment if she is considered not of child bearing<br> potential.<br><br> - Males and females of childbearing potential must utilize a standard contraception<br> method throughout the trial and up to 120 days after the last dose of treatment on<br> study.<br><br> - NOTE: Women of childbearing potential and men with female spouses of<br> childbearing potential must agree to use two methods of reliable contraception<br> simultaneously or to practice complete abstinence from heterosexual contact<br> prior to study entry, while receiving treatment, and for 4 months after<br> undergoing treatment. One method must include a highly effective method such as<br> an intrauterine device, hormonal (birth control pills, injections or implants),<br> tubal ligation or partner's vasectomy. The other method can be an additional<br> hormonal therapy or barrier method such as a male condom, diaphragm or cervical<br> cap. Should a woman become pregnant or suspect she is pregnant while she or her<br> partner is participating in the study, she should inform her treating physician<br> immediately<br><br>Exclusion Criteria:<br><br> - Current or planned participation in a study of an investigational agent or using an<br> investigational device.<br><br> - Has tumor primarily localized to the brainstem or spinal cord<br><br> - Has presence of diffuse leptomeningeal disease or extracranial disease.<br><br> - Surgical procedure (including open biopsy, surgical resection, wound revision, or<br> any other major surgery involving entry into a body cavity) or significant traumatic<br> injury within 28 days prior to first study treatment<br><br> - Minor surgical procedure (e.g. stereotactic biopsy or shunt placement) within 7 days<br> of first study treatment, placement of vascular access within 2 days of first study<br> treatment<br><br> - Expected to have surgery other than the neurosurgical procedure intended for the GBM<br> lesion during study treatment period<br><br> - Prior stereotactic radiotherapy (Note: those who have had biopsy proven tumor<br> recurrence at a site of SRS treatment should be considered eligible if approved by<br> the study central Investigator)<br><br> - Prior anti-angiogenic therapy including VEGF sequestering agents (i.e. bevacizumab,<br> aflibercept, etc.) or VEGFR inhibitors (cedirinib, pazopanib, sunitinib, sorafenib,<br> etc.)<br><br> - Prior administration of the study drug VB-111<br><br> - Concomitant medication that may interfere with study results (e.g. immunosuppressive<br> agents other than inhaled, topical or intra-articular steroids or a stable or<br> decreasing dose of oral corticosteroids of up to <2 mg/day dexamethasone equivalent)<br><br> - Known active second malignancy. Exceptions include non-melanoma skin cancers,<br> non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular<br> carcinoma in situ of the breast. Participants are not considered to have currently<br> active malignancy if they have completed anticancer therapy and have been disease<br> free for greater than 2 years prior to screening<br><br> - Uncontrolled intercurrent illness including but not limited to ongoing or active<br> infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac<br> arrhythmia, or psychiatric illness/social situations that would limit compliance<br> with study requirements<br><br> - History of stroke or transient ischemic attack within 6 months prior to<br> randomization<br><br> - Evidence of CNS hemorrhage CTCAE grade 2 or above on screening MRI<br><br> - Active cardiac disease w

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Tumor infiltrating T cell (TIL) density;Rate of Dose Limiting Toxicity

Secondary Outcome Measures

Name	Time	Method
6-month progression-free survival;Overall Survival