A Phase 2, Randomized, Open-Label Study of Nivolumab Combined with Ipilimumab Versus Sunitinib Monotherapy in Subjects with Previously Untreated and Advanced (unresectable or metastatic) non-clear Cell Renal Cell Carcinoma

Phase 1

• Conditions: The primary objective of the study is to compare the OS rate at 12 months of Nivolumab combined with Ipilimumab to Sunitinib monotherapy in patients with previously untreated and advanced non clear cell renal cell carcinoma; MedDRA version: 20.0 Level: LLT Classification code 10038415 Term: Renal cell carcinoma stage unspecified System Organ Class: 100000072939; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-000706-12-GB
• Lead Sponsor: Goethe University Frankfurt

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-06-02
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 306

Inclusion Criteria

1. Informed consent
a. Signed Written Informed Consent 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. Patients 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 the relevant WHO classification
b) Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC
c) Patients must be fit to be treated (>70% based on the Karnofsky classification)
d) Measurable disease as per standard RECIST criteria
e) Tumor tissue must be available and sent to the central pathological reviewer in order to confirm the diagnosis.
f) Patients with all risk categories (favourable versus intermediate versus poor risk group) will be eligible for the study. Patients will be categorised according to non-clear cell RCC subgroups based on the International Metastatic RCC Database Consortium (IMDC) criteria
3. Age and Reproductive Status
a) Males and Females, >18 years of age
b) Women of reproductive potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug
c) Women must not be breastfeeding
d) Women of reproductive potential must agree to follow instructions for method(s) of contraception
e) Males who are sexually active with women of reproductive potential must agree to follow instructions for method(s) of contraception
f) Azoospermic males and women of reproductive potential who are continuously not heterosexually active are exempt from contraceptive requirements. However they must still undergo pregnancy testing as described in this section.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
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

Exclusion Criteria

1) Any active brain metastases requiring systemic corticosteroids
2) Tumors with a clear-cell component of > 50%
Medical History and Concurrent Diseases
3) Prior systemic treatment with vascular endothelial growth factor (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.
4) Prior treatment with immunotherapy. More specifically, 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.
5) 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.
6) 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.
7) Uncontrolled adrenal insufficiency.
8) 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
9) Poorly controlled hypertension (defined as systolic blood pressure (SBP) of = 150 mmHg or diastolic blood pressure (DBP) of = 90 mmHg), despite antihypertensive therapy.
10) 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.
11) History of cerebrovascular accident including transient ischemic attack within the past 12 months.
12) History of deep vein thrombosis (DVT) unless adequately treated with low molecular weight heparin
13) History of pulmonary embolism within the past 6 months unless stable, asymptomatic, and treated with low molecular weight heparin for at least 6 weeks. 14) History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.
15) Serious, non-healing wound or ulcer.
16) Evidence of active bleeding or bleeding susceptibility; or medically significant hemorrhage within prior 30 days.
17) Any requirement for anti-coagulation, except for low molecular weight heparin.
18) 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 brea

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified