A Phase 2, Randomized, Open-Label Study of Nivolumab Combined with Ipilimumab Versus Standard of Care in Subjects with Previously Untreated and Advanced (unresectable or metastatic) non-clear Cell Renal Cell Carcinoma
- Conditions
- To compare the of OS rate at 12 months of Nivolumab combined with Ipilimumab tostandard of care in patients with previously untreated and advanced non-clear cell RCCMedDRA version: 20.0Level: LLTClassification code 10038415Term: Renal cell carcinoma stage unspecifiedSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-000706-12-CZ
- Lead Sponsor
- Goethe University Frankfurt
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 306
1. Signed Written Informed Consent
a) Subjects must have signed and dated an IRB/IEC approved
written informed consent form in accordance with regulatory and
institutional guidelines. This must be obtained before the
performance of any protocol related procedures that are not part
of normal subject care.
b) Subjects must be willing and able to comply with scheduled
visits, treatment schedule, laboratory testing, and other
requirements of the study.
2. Target Population
a) Histological confirmation of non-clear RCC with at least 50%
non-clear cell component according to actual WHO
classification36
b) Advanced (not amenable to curative surgery or radiation therapy)
or metastatic (AJCC Stage IV) RCC
c) Karnofsky > 70%
d) Measurable disease as per RECIST v 1.1 documented by an
English radiology report
e) Tumor tissue (FFPE archival or recent acquisition) must be
available and sent to the central pathological in order to confirm
the diagnosis. (Note: Fine Needle Aspiration [FNA] and bone
metastases samples are not acceptable for submission).
f) Patients with all risk categories will be eligible for the study.
Patients will be stratified for papillary or non-papillary non-clear
cell histology and IMDC risk score Patients will be categorized
according to favorable versus intermediate versus poor risk status
at registration according to the International Metastatic RCC
Database Consortium (IMDC) criteria:
i. KPS equal to 70%
ii. Less than 1 year from diagnosis to randomization
iii. Hemoglobin less than the lower limit of normal (LLN)
iv. Corrected calcium concentration greater than the upper limit of normal (ULN)
v. Absolute neutrophil count greater than the ULN
vi. Platelet count greater than the ULN
If none of the above factors are present, subjects are only eligible for the
favorable-risk cohort, if 1-2 factors are present subjects are categorized
as intermediate risk and > 3 factors as poor risk.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6
1. Target Disease Exceptions
a) Any active brain metastases requiring systemic corticosteroids.
Baseline imaging of the brain by MRI is required in patients with
clinical signs of potential CNS involvement within 28 days prior
to randomization.
b) Tumors with a clear-cell component of > 50%
Medical History and Concurrent Diseases
c) Prior systemic treatment with VEGF or VEGF receptor targeted
therapy (including, but not limited to, Sunitinib, pazopanib,
axitinib, tivozanib, and bevacizumab) or prior treatment with an
mTOR inhibitor or cytokines.
d) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-
CD137, or anti-CTLA-4 antibody, or any other antibody or drug
specifically targeting T-cell co-stimulation or checkpoint
pathways.
e) Administration of an immune checkpoint inhibitor as standard of
care
f) Any active or recent history of a known or suspected
autoimmune disease or recent history of a syndrome that required
systemic corticosteroids (> 10 mg daily prednisone equivalent) or
immunosuppressive medications except for syndromes which
would not be expected to recur in the absence of an external
trigger. Subjects with vitiligo or type I diabetes mellitus or
residual hypothyroidism due to autoimmune thyroiditis only
requiring hormone replacement are permitted to enroll.
g) Any condition requiring systemic treatment with corticosteroids
(> 10 mg daily prednisone equivalents) or other
immunosuppressive medications within 14 days prior to first
dose of study drug. Inhaled steroids and adrenal replacement
steroid doses > 10 mg daily prednisone equivalents are permitted
in the absence of active autoimmune disease.
h) Uncontrolled adrenal insufficiency.
i) Ongoing symptomatic cardiac dysrhythmias, uncontrolled atrial
fibrillation, or prolongation of the Fridericia corrected QT
(QTcF) interval defined as > 450 msec for males and > 470 msec
for females, where QTcF = QT / 3vRR
j) Poorly controlled hypertension (defined as systolic blood pressure (SBP) of ??150 mmHg or diastolic blood pressure
(DBP) of ??90 mmHg), despite antihypertensive therapy.
k) History of any of the following cardiovascular conditions within
12 months of enrollment: cardiac angioplasty or stenting,
myocardial infarction, unstable angina, coronary artery by-pass
graft surgery, symptomatic peripheral vascular disease, class III
or IV congestive heart failure, as defined by the New York Heart
Association.
l) History of cerebrovascular accident including transient ischemic
attack within the past 12 months.
m) History of deep vein thrombosis (DVT) unless adequately treated
with low molecular weight heparin
n) History of pulmonary embolism within the past 6 months unless
stable, asymptomatic, and treated with low molecular weight
heparin for at least 6 weeks.
o) History of abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess within the past 6 months.
p) Serious, non-healing wound or ulcer.
q) Evidence of active bleeding or bleeding susceptibility; or
medically significant hemorrhage within prior 30 days.
r) Any requirement for anti-coagulation, except for low molecular
weight heparin.
s) Prior malignancy active within the previous 3 years except for
locally curable cancers that have been apparently cured, such as
basal or squamous cell skin cancer, superficial bladder cancer, or
carcinoma in situ of the prostate, cervix, or breast.
t) Known history of testing positive for human immunodeficiency
virus (HIV) or known acquired immunodeficiency s
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method