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Randomized Phase-II Study of Nivolumab Plus Ipilimumab vs. Standard of Care in Untreated and Advanced Non-clear Cell RCC | Clinical Trials | Clareo Health

COMPLETEDPHASE2

Randomized Phase-II Study of Nivolumab Plus Ipilimumab vs. Standard of Care in Untreated and Advanced Non-clear Cell RCC

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 (nccRCC)

NCT03075423•Goethe University

View on ClinicalTrials.gov

Summary

Detailed Description

SUNNIFORECAST (Standard of Care vs. Nivolumab + Ipilimumab as First line treatment of renal cell cancer of non-clear cell subtypes) is a Phase II, randomized, open-label investigator initiated trial (IIT) of Nivolumab (BMS-936558) combined with Ipilimumab vs standard of care in subjects with previously untreated and advanced (unresectable or metastatic) non-clear cell renal cell carcinoma (nccRCC). In the Phase I setting, Nivolumab combined with Ipilimumab has demonstrated substantially greater clinical activity, as measured by objective response rate (ORR), than either agent alone in metastatic RCC (mRCC). Given the durability of responses associated with immunotherapies, Nivolumab combined with Ipilimumab is hypothesized to lead to greater clinical benefit, as measured by overall survival (OS) rate at 12 months as primary endpoint and OS at 6 months and 18 months, progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) as secondary endpoints compared to standard of care in this patient population. This study will allow for direct comparison of OS rate at 12 months between both arms.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Signed Written Informed Consent a) Subjects must have signed and dated an approved written informed consent form according to the Institutional Review Board (IRB) and 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 cell renal cell carcinoma (nccRCC) with at least 50% non-clear cell component according to actual World Health Organization (WHO) classification.
•b) Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) nccRCC c) Performance status: Karnofsky (KPS) \> 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 reviewer (see Table 6) 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. \< 1 year from diagnosis to randomization iii. Hemoglobin \< 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.
•3. Age and Reproductive Status
•a) Males and Females, \> 18 years of age b) 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 for a period of 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo five half-lives. The terminal half-lives of Nivolumab and Ipilimumab are up to 25 days and 18 days, respectively. The terminal half-life of the active metabolite of Sunitinib is up to 110 hours. The terminal half-life of other Standard of Care agents has to be derived from the product information.
•i. WOCBP randomized to receive Nivolumab + Ipilimumab 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 investigational drug.
•ii. WOCBP randomized to receive the Standard of Care agent should use an adequate method to avoid pregnancy for 8 weeks (30 days plus the time required for the active metabolite of the Standard of Care agent to undergo five half-lives) e) Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for a period of 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo five half-lives. The terminal half lives of Nivolumab and Ipilimumab are up to 25 days and 18 days, respectively. The terminal half-life of the active metabolite of Sunitinib is up to 110 hours.
+22 more criteria

Exclusion Criteria

•1\. Target Disease Exceptions
•1. Any active brain metastases requiring systemic corticosteroids. Baseline imaging of the brain by MRI is required in patients with clinical signs of potential central nerve system (CNS) involvement within 28 days prior to randomization.
•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 an immune checkpoint inhibitor as anti-programmed cell death (PD)PD-1, anti-PD-L1, anti-PD-L2, anti cytotoxic T-lymphocyte-associated Protein 4 (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 / 3√RR
+25 more criteria

Locations (30)

Gent University Hospital (Universitair Ziekenhuis Gent)

Ghent, Belgium

University Hospital Hradec Králové

Hradec Králové, Czechia

Thomayer Hospital

Prague, Czechia

Centre Hospitalier Universitaire de Bordeaux

Bordeaux, France

Centre François Baclesse

Caen, France

Centre Hospitalier Départemental de Vendée

La Roche-sur-Yon, France

Centre Leon Berard

Lyon, France

Institut Gustave Roussy

Paris, France

Les Hoptaux Universitaires de Strasbourg

Strasbourg, France

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Key Dates

Start Date

November 1, 2017

Primary Completion Date

November 23, 2023

Completion Date

November 23, 2023

Last Updated

September 26, 2025

Enrollment

316

ACTUAL participants

Conditions

Metastatic Renal Cell Carcinoma

Interventions

Ipilimumab plus nivolumab

DRUG

Standard Therapy

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 26, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Randomized Phase-II Study of Nivolumab Plus Ipilimumab vs. Standard of Care in Untreated and Advanced Non-clear Cell RCC

Inclusion Criteria

Exclusion Criteria

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