A Phase 3, Randomized, Controlled, Double-Arm, Open-Label, Multi-center Study of VB-111 Combined with Bevacizumab vs. Bevacizumab Monotherapy in Patients with Recurrent Glioblastoma

Study ID
STU 032016-005

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • UT Southwestern Moncrieff Cancer Center
  • Zale Lipshy University Hospital

Contact
Rafael Leon
214/648-1929
Rafael.Leon@UTSouthwestern.edu

Principal Investigator
Edward Pan, M.D.

Summary

This will be a prospective, randomized, controlled, double-arm, open label, multi-center,
Phase 3 study, measuring the efficacy, safety and tolerability of multiple doses of
intravenously administered VB-111 in combination with bevacizumab as compared to
bevacizumab monotherapy in patients with recurrent GBM.

Patients will be screened for eligibility and then, up to 28 days later, at the baseline
visit, randomized to one of two treatment groups in a 1:1 ratio (investigative arm to
control arm). Randomization will be stratified according to age at randomization ([LessThanorequalTo] 60
years, [Less Than] 60 years), KPS ([Less Than] 80, [GreaterThanorequalTo] 80) and progression (1st progression, 2nd
progression). The experimental arm will receive VB-111 administered as an
intravenous infusion of 1x10^13 VPs every 8 weeks, combined with bevacizumab
10mg/Kg every 2 weeks. The control arm will receive monotherapy with bevacizumab
10mg/Kg every 2 weeks until progression. upon an increase in tumor measurements
greater than 50% or any confirmed T2/FLaiR and/or clinical deterioration (based on
the Rano definition of these components), following administration of VB-111 in
combination with bevacizumab in the experimental arm or bevacizumab alone in the
control arm, patients will discontinue treatment with study medication and will be
treated at discretion of their treating physician. There will be no cross over from
control arm to VB-111.

The patients will remain in the study until discontinuation due to disease status as
defined above or withdrawal. Thereafter, all efforts will be made to collect post-study
MRis for analysis, health related quality of life measures, anti-cancer treatment and
follow-up for survival will continue until the patient expires.

Continuous variables will be described as the mean, median, standard deviation and range of n observations. Categorical data will be described with contingency tables including frequency and percentage. individual patient listings will be generated and presented.

-Primary efficacy endpoint
overall Survival (oS) is defined as the time from randomization until death from any
cause. Patients will be followed for survival status after completion or removal from the
study for progression or withdrawal.

-Secondary efficacy endpoints
Progression Free Survival (PFS) is defined as the time from randomization until
objective tumor progression, assessed according to Rano.
Tumor response is measured by Rano Criteria including complete response, partial
response, stable disease and progression.

-Tertiary efficacy endpoints
Tumor growth rate is defined by the rate of change (slope) of tumor size in each patient.
Tumor size will be determined as the product of the perpendicular dimensions of the
tumor.

Participant Eligibility

-Inclusion Criteria
1. First or second progression of Glioblastoma (according to RANO Criteria, which
is based on radiographic measurable T1 contrast enhancing progression, see
Appendix I) following standard of care treatment with temozolomide and
radiation;
2. A histologically confirmed diagnosis of GBM. Patients with recurrent disease
whose diagnostic pathology confirmed GBM will not need re-biopsy;
3. Measurable disease by RANO criteria at progression;
4. Patients >=18 years of age;
5. Patients with surgically resectable disease at recurrence may be enrolled,
provided they have measureable disease at time of study enrollment. An
interval of at least 28 days is required between prior surgical resection and
study enrollment;
6. An interval of at least 12 weeks between prior radiotherapy or at least 23 days
from prior chemotherapy, 42 days from nitrosoureas and enrollment in this
protocol;
7. Recovered to Grade 1 or less from the toxic effects of any earlier intervention;
8. Karnofsky Performance Score of at least 70%;
9. Life expectancy of at least 3 months;
10. Adequate renal, liver, and bone marrow function according to the following
criteria:

* Absolute neutrophil count >=1500 cells/ml,

* Platelets >= 100,000 cells/ml,

* Total bilirubin within upper limit of normal (ULN),

* Aspartate aminotransferase (AST) <= 2.0 X ULN,

* Serum creatinine level <= ULN or creatinine clearance >= 50 ml/min for
patients with creatinine levels above normal limits (creatinine clearance
calculated by the Cockcroft-Gault formula, see Appendix II),

* PT, PTT (in seconds) not to be prolonged beyond >20% of the upper
limits of normal;
11. Patients already administering steroids must be on a stable or decreasing dose
for at least 1 week prior to entry with no anticipation of a need to increase the
steroid dose throughout the study;
12. Ability to understand and willingness to sign a written informed consent
document;
13. Males and females of childbearing potential must utilize a standard
contraception method throughout the course of the trial.

* Women of childbearing potential must have a negative serum betahuman
chorionic gonadotropin pregnancy test at initial screening and/or
within 7 days prior to Day 1.

* 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. One method must include a highly effective
method such as an intrauterine device, hormonal (birth control pills,
injections or implants), tubal ligation or partner[Single Quote]s vasectomy and one can
be an additional (barrier method such as a male condom, diaphragm or
cervical cap or hormonal) prior to study entry, while receiving treatment
and for 4 months after undergoing treatment. Should a woman become
pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician
immediately.
o A woman is considered not to be of childbearing potential if
she is postmenopausal, defined by amenorrhea of >=12
months duration and age >= 45 years, or has undergone
hysterectomy and/or bilateral oophorectomy.