A randomized phase II study in which therapy is either switched to Nivolumab after 3 months of treatment or therapy is continued with a tyrosine kinase inhibitor in patients with metastatic renal cell carcinoma (RCC) and disease control

Phase 1

Conditions: advanced or metastatic renal cell carcinoma (RCC)
MedDRA version: 21.0Level: PTClassification code 10073251Term: Clear cell renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: PTClassification code 10050513Term: Metastatic renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: PTClassification code 10067946Term: Renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: LLTClassification code 10038409Term: Renal cell carcinoma NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-002170-13-DE

Lead Sponsor: AIO-Studien-gGmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 244

Inclusion Criteria

1. Written informed consent and any locally-required
authorization (EU Data Privacy Directive in the EU) obtained
from the subject prior to performing any protocol-related
procedures, including screening evaluations.
2. Subject is willing and able to comply with the protocol for the
duration of the study including undergoing treatment and
scheduled visits and examinations including follow up.
3. Age = 18 years at time of study entry
4. ECOG performance status 0-2.
5. Metastatic or locally advanced RCC with clear cell
component, not amenable to surgery with curative intention.
6. First-line treatment with a TKI for 10-12 weeks (limited to
sunitinib or pazopanib).
7. Patients with measurable disease (at least one unidimensionally
measurable target lesion by CT-scan or MRI)
according to modified Response Evaluation Criteria in Solid
Tumors (RECIST 1.1). If prior palliative radiotherapy to
metastatic lesions: = 1 measurable lesion that has not been
irradiated. Patients with bone lesions as the only measurable
lesion are eligible, provided that lesions consist of soft tissue,
which is assessed via CT or MRI.
8. Documented partial response or stable disease to first-line
TKI exposure at 10-12 weeks.
9. Prior therapies other than indicated in the exclusion critiria
and surgeries are allowed if completed 4 weeks (for minor surgery and palliative radiotherapy for bone pain: 2 weeks)
prior to start of treatment and patient recovered from toxic
effects.
10. Adequate blood count, liver-enzymes, and renal function
(obtained no later than 14 days prior to start of study
treatment):
? WBC = 2000/µL
? Neutrophils = 1500/µL
? Platelets = 100 x103/µL
? Hemoglobin > 9.0 g/dL
? Serum creatinine = 1.5 x ULN or creatinine
clearance (CrCl) = 40 mL/min (if 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 = (140 - age in years) x weight in kg x 1.00/
72 x serum creatinine in mg/dL
? AST/ALT = 3 x ULN
? Total Bilirubin = 1.5 x ULN (except subjects
with Gilbert Syndrome, who can have total
bilirubin < 3.0 mg/dL)
11. Women of childbearing potential (WOCBP) must use
appropriate method(s) of contraception. WOCBP should use
an adequate method to avoid pregnancy for 23 weeks (30
days plus the time required for nivolumab to undergo five
half-lives) after the last dose of nivolumab.
12. Women of childbearing potential 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
nivolumab
13. Men who are sexually active with WOCBP must use any
contraceptive method with a failure rate of less than 1% per
year. Men receiving nivolumab and who are sexually active
with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational
product. Women who are not of childbearing potential (ie,
who are postmenopausal or surgically sterile as well as
azoospermic) men do not require contraception.
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 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 164

Exclusion Criteria

1. Prior systemic therapy other than 10-12 weeks SOC TKI
treatment for advanced or metastatic RCC.
2. Standard of care 1st-line TKI treatment for advanced or
metastatic RCC for longer than 12 weeks.
3. Complete remission (CR) or progression during SOC TKI 1st-
line treatment.
4. Termination of first-line treatment with TKI due to intolerance
5. Previous malignancy (other than renal cell cance
cancer of the skin, pre-invasive cancer of the cervix, T1a
prostate carcinoma or superficial bladder tumor [Ta, Tis and
T1] are exempted.
6. Brain metastases mandating active treatment. Subjects with
brain metastases are eligible if metastases have been treated
and there is no magnetic resonance imaging (MRI) evidence
of progression for 4 weeks after treatment is completed and
within 28 days prior to the first dose of nivolumab
administration. There must also be no requirement for
immunosuppressive doses of systemic corticosteroids (> 10
mg/day prednisone equivalents) for at least 2 weeks prior to
study drug administration.
7. Prior therapy with anti-tumor vaccines or other immunostimulatory
antitumor agents.
8. Administration of a live, attenuated vaccine within 4 weeks of
start of therapy
9. Any previous treatment with an anti-PD-1, anti-PD-L1, anti-
PD-L2, anti-CTLA-4 antibody, or any other antibody or drug
specifically targeting T-cell co-stimulation or immune
checkpoint pathways
10. Subjects must have recovered from the effects of major
surgery or significant traumatic injury at least 14 days before
the first dose of study treatment.
11. Patients should be excluded if they have an active, known or
suspected autoimmune disease. NOTE: Subjects are
permitted to enroll if they have vitiligo, type I diabetes
mellitus, residual hypothyroidism due to autoimmune
condition only requiring hormone replacement, psoriasis not
requiring systemic treatment, or conditions not expected to
recur in the absence of an external trigger
12. Patients should be excluded if they have a condition requiring
systemic treatment with either corticosteroids (> 10 mg daily
prednisone equivalents) or other immunosuppressive
medications within 14 days of study drug administration.
NOTE: Inhaled or topical steroids and adrenal replacement
doses > 10 mg daily prednisone equivalents are permitted in
the absence of active autoimmune disease.
13. Known chronic infection (i.e. hepatitis B or C, HIV)
14. Patients should be excluded if they have been positively
tested for hepatitis B virus surface antigen (HBV sAg) or
hepatitis C virus ribonucleic acid (HCV antibody) indicating
acute or chronic infection.
15. Patients should be excluded if they have a known history of
testing positive for human immunodeficiency virus (HIV) or a
known acquired immunodeficiency syndrome (AIDS).
16. History of severe hypersensitivity reaction to any monoclonal antibody or any constituent of the product.
17. Uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart
failure, uncontrolled hypertension, unstable angina pectoris,
cardiac arrhythmia, active peptic ulcer disease or gastritis,
active bleeding diatheses including any subject known to
have a psychiatric illness/social situations that would limit
compliance with study requirements or compromise the
ability of the subject to give written informed consent
18. Uncontrolled severe hypertension (failure of diastolic blood
pressure to fall below 95 mmHg under adequate medication)
19. Curre

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the survival benefit from an early switch approach from sunitinib or pazopanib to nivolumab (anti-angiogenic to immunotherapy switch);Secondary Objective: •to compare efficacy of early switch to nivolumab vs. continuation of either sunitinib or pazopanib <br>•to compare health-related quality of life (HR-QoL) during TKI and nivolumab treatment after early switch<br>•to assess the influence of response to previous TKI treatment on nivolumab efficacy<br>•to assess safety and toxicity<br>;Primary end point(s): overall survival;Timepoint(s) of evaluation of this end point: after death of the patient<br>

Secondary Outcome Measures

Name	Time	Method

Related Trials