A Randomized Phase 3 Open Label Study of Nivolumab versus Bevacizumab and a Safety Study of Nivolumab or Nivolumab in Combination with Ipilimumab in Adult Subjects with Recurrent Glioblastoma (GBM)
- Conditions
- Glioblastoma
- Registration Number
- NL-OMON45042
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 14
Main Inclusion Criteria
Subjects must:
a)Provide signed written informed consent before the performance of any
protocol related procedures that are not part of normal subject care.
b)Be willing and able to comply with scheduled visits, treatment schedule, lab
tests, and other requirements of the study including disease assessment by
MRI., TARGET POPULATION
a)Must have histologically confirmed diagnosis of Grade IV malignant glioma.
b)Must have been treated previously with at least radiotherapy and temozolomide.
c)Must have documented first recurrence of Glioblastoma by biopsy or MRI
performed within 21 days of randomization per RANO criteria.
d)If first recurrence of GBM is documented by MRI, an interval of at least 12
weeks after the end of prior radiation therapy is required unless there is
either i) histopathologic confirmation of recurrent tumour, or ii) new
enhancement on MRI outside of the radiotherapy treatment field.
e) Cohort 1 and 1b only: At least one measureable GBM leasion prior to
randomization that meets the following criteria: i) contrast enhancing and
clearly defined, bi-dimensionally measurable margins AND ii) at least two
perpendicular diamteres measuring >= 10mm x >= 10mm.
f)An interval of 28 days and full recovery since surgical resection prior to
randomization.
g)An interval of weeks after the last administration of any other treatment
for GBM
h)Must have a Karnofsky performance score of 70 or higher.
i)Must have a life expectancy of greater than or equal to 12 weeks.
j)Subject Re-enrollment: This study permits the re-enrollment of a subject that
has
discontinued the study as a pre-treatment failure (ie, subject has not been
randomized /has not been treated). If re-enrolled, the subject must be
re-consented., 3. AGE AND REPRODUCTIVE STATUS
a) Men and women >=18 years of age.
b) Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within
24 hours prior to the start of study drug.
c) Women must not be breastfeeding
d) WOCBP must agree to follow instructions for method(s) of contraception from
the time of enrollment for the duration of treatment with nivolumab plus 5
half-lives of nivolumab plus 30 days (duration of ovulatory cycle) for a total
of 23 weeks post treatment completion.
e) Men who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for
the duration of treatment with nivolumab plus 5 half-lives of nivolumab plus 90
days (duration of sperm turnover)
for a total of 31 weeks post-treatment completion.
f) Azoospermic males and WOCBP who are continuously not heterosexually active
are exempt from
contraceptive requirements. However they must still undergo pregnancy testing
as described in these sections, 4. Screening laboratory values must meet the
following criteria and should be obtained within
14 days prior to first dose:
i) Whole Blood Count >= 2000/µL
ii) Neutrophil Count >= 1500/µL
iii) Platelets >=100 x103/µL
iv) Hemoglobin > 9.0 g/dL
v) Serum creatinine <= 1.5 x ULN or creatinine clearance (CrCl)>=40 ml/min
(measured
using the Cockcroft-Gault formula below):
Female CrCl = (140 - age in years) x weight in kg x 0.85/72 x serum creatinine
in mg/dL
Male CrCl = (14
Subjects must not:
a)Have had more than one recurrence of Glioblastoma
b)Have a presence of extracranial metastatic or leptomeningeal disease.
c)Have had a diagnosis of secondary glioblastoma., 2.
a)Have any serious or uncontrolled medical disorder that, in the opinion of the
investigator, may increase the risks associated with participating in this
study, or study drug administration, or impair the subject*s ability to receive
the therapy or interfere with the interpretation of study results.
b)Have an active, known or suspected autoimmune disease.
c)Have had previous radiation therapy with anything other than standard
radiation therapy.
d)Subjects requiring escalating or chronic supraphysiologic doses of
corticosteroids for control of their disease at randomization are exlcuded.
e)Have had previous treatment with carmustine wafer except when administered as
first line treatment and at least 6 months prior to randomization
f)Previous treatment with Bevacizumab or other VEGF or anti-angiogenic
treatment.
g)Previous treatment with a PD-1 or CTLA-4 targeted therapy.
h)Evidence of > Grade 1 CNS hemorrhage on the baseline MRI scan;
i) Inadequately controlled hypertension (defined as systolic blood pressure>=
150 mmHg
and/or diastolic blood pressure >=100 mmHg) within 28 days of first study
treatment;
j) Prior history of hypertensive crisis, hypertensive encephalopathy,
reversible posterior
leukoencephalopathy syndrome (RPLS);
k) Prior history of gastrointestinal diverticulitis, perforation, or abscess;
l) Clinically significant (ie, active) cardiovascular disease, for example
cerebrovascular
accidents<= 6 months prior to study enrollment, myocardial infarction <= 6
months prior to
study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or
greater congestive heart failure (CHF), or serious cardiac arrhythmia
uncontrolled by
medication or potentially interfering with protocol treatment;
m) History or evidence upon physical/neurological examination of central
nervous system
disease (eg, seizures) unrelated to cancer unless adequately controlled by
medication or
potentially interfering with protocol treatment;
n) Significant vascular disease (eg, aortic aneurysm requiring surgical repair
or recent
arterial thrombosis) within 6 months prior to start of study treatment. Any
previous
venous thromboembolism > NCI CTCAE Grade 3;
o) History of pulmonary hemorrhage/hemoptysis >= grade 2 (defined as >= 2.5 mL
bright red
blood per episode) within 1 month prior to randomization;
p) History or evidence of inherited bleeding diathesis or significant
coagulopathy at risk of
bleeding (ie, in the absence of therapeutic anticoagulation);
q) Current or recent (within 10 days of study enrollment) use of
anticoagulants that,in the opinion of the investigator, would place the subject
at sginificant risk for bleeding. Prophylactic use of anticoagulants is allowed;
r) 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, or anticipation of need for
major surgical
procedure during the course of the study;
s) Minor surgical procedure (eg, stereotactic biopsy within 7 days of f
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective of Cohort 2 is to compare overall survival between<br /><br>Nivolumab versus Bevacizumab in subjects with recurrent GBM.</p><br>
- Secondary Outcome Measures
Name Time Method