Study of Front Line Therapy With Nivolumab and Salvage Nivolumab + Ipilimumab in Patients With Advanced Renal Cell Carcinoma

NCT03117309 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN GU16-260
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 12

Brief Summary

Phase II trial of nivolumab in 120 treatment naïve patients with ccRCC.

Conditions

Advanced Renal Cell Carcinoma

Keywords

Nivolumab; Ipilimumab; OPDIVO; IgG1 kappa immunoglobulin

Outcome Measures

Primary Outcomes (1)

• 1-year Progression Free Survival (PFS) Rate for ccRCC Patients

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. 1-year Progression-Free Survival (PFS) Rate refers to the percentage of patients who have not experienced disease progression or death from any cause within one year of starting treatment. The 1-year PFS rate of nivolumab in treatment-naïve patients with clear cell renal cell carcinoma (ccRCC) was assessed according to tumor PD-L1 expression levels.

  1 year

Secondary Outcomes (5)

• Objective Response Rate for ccRCC Patients Treated With Nivolumab Monotherapy

  Up to 39 Months

• Objective Response Rate (ORR) for ccRCC Patients Treated With Nivolumab and Ipilimumab

  Up to 39 Months

• Clinical Activity for nccRCC Patients

  Up to 39 Months

• 1-year Progression Free Survival (PFS) Rate for nccRCC Patients

  1 year

• Number of Participants With Adverse Events

  Up to 28 months

Study Arms (2)

PART A: Nivolumab

EXPERIMENTAL

Nivolumab 240mg; Nivolumab 360mg

Drug: Nivolumab 240 mg; Drug: Nivolumab 360mg

PART B: Nivolumab + Ipilimumab

EXPERIMENTAL

Nivolumab 3mg/kg and Ipilimumab 1mg/kg; Nivolumab 360mg

Drug: Ipilimumab 1mg/kg; Drug: Nivolumab 3mg/kg; Drug: Nivolumab 360mg

Interventions

Nivolumab 240 mg DRUG

PART A Nivolumab 240 mg IV every 2 weeks x 6 then initial disease assessment

Also known as: OPDIVO

PART A: Nivolumab

Ipilimumab 1mg/kg DRUG

Ipilimumab 1 mg/kg every 3 weeks x 4

Also known as: Yervoy

PART B: Nivolumab + Ipilimumab

Nivolumab 3mg/kg DRUG

In combination with Ipilimumab

Also known as: OPDIVO

PART B: Nivolumab + Ipilimumab

Nivolumab 360mg DRUG

Continue Nivolumab 360 mg IV every 3 weeks

Also known as: OPDIVO

PART A: Nivolumab; PART B: Nivolumab + Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed advanced RCC (any histology). Collecting duct tumors and tumors originating from the renal pelvis or upper urinary tract are considered of urothelial origin and are excluded from this protocol.
• Patients must have at least one measurable site of disease, per RECIST 1.1, that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
• Archival tissue of a metastatic lesion obtained within 1 year prior to study registration (within 4 weeks preferred) and tumor tissue from nephrectomy is required if available. In addition to archival tissue of a metastatic lesion and nephrectomy, patients must have at least one site of disease (not including bone metastases) accessible for biopsy. If biopsy/resection of a new lesion or primary tumor and slow freezing of fresh tissue for single cell RNAseq study (as specified in the CLM) is not feasible, the subject is not eligible for the study. All biopsies must be core needle or excisional. Fine needle aspirate is not acceptable. NOTE: The tissue collected from a surgical resection or multiple core biopsies of either a metastatic lesion or primary tumor for the slow freezing of fresh tissue after the patient has signed consent for the study could also be used for collecting the FFPE specimens.
• ECOG performance status 0-2.
• Age ≥ 18 years.
• Have signed the current approved informed consent form.
• Patients must have adequate organ function within 14 days prior to study entry as evidenced by screening laboratory values that must meet the following criteria:
• Hematological:
• White blood cell (WBC) ≥ 2000/µL
• Absolute Neutrophil Count (ANC) ≥ 1500/μL
• Platelets (Plt) ≥ 100 x103/μL
• Hemoglobin (Hgb) \> 9.0 g/dL (with or without transfusion)
• Renal:
• Serum Creatinine ≤ 1.5 x ULN; if creatinine \> 1.5, subject must demonstrate CrCl as outlined below.
• Calculated creatinine clearance ≥ 40 mL/min using Cockcroft-Gault formula

You may not qualify if:

• Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for 2 weeks of more after treatment is complete 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.
• Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected without recurrence or treated with SRS without progression x 4 weeks.
• Patients should be excluded if they have an active, known or suspected autoimmune disease. 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.
• 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. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
• Active infection requiring systemic therapy
• Has any other medical or personal condition that, in the opinion of the site investigator, may potentially compromise the safety or compliance of the patient, or may preclude the patient's successful completion of the clinical trial
• Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Allergies and Adverse Drug Reaction
• History of allergy to study drug components
• History of severe hypersensitivity reaction to any monoclonal antibody
• Known additional malignancies within the past 3 years (excluding basal of squamous cell skin cancers, CIS or localized prostate cancer that has been treated or is being observed)
• Must meet eligibility criteria for initiation of Part A with the exception of being allowed to have prior nivolumab in Part A of this protocol
• Must have evidence of either RECIST 1.1 defined Disease Progression or Stable Disease 1 year after initiating nivolumab therapy

Sponsors & Collaborators

• Michael B. Atkins, MD: lead
• Bristol-Myers Squibb: collaborator
• Hoosier Cancer Research Network: collaborator

Study Sites (12)

Yale University, Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University Feinberg Schooll Of Medicine

Chicago, Illinois, 60611, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Beth Isreal Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44915, United States

Location

Univeristy of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (2)

• Atkins MB, Jegede OA, Haas NB, McDermott DF, Bilen MA, Stein M, Sosman JA, Alter R, Plimack ER, Ornstein MC, Hurwitz M, Peace DJ, Signoretti S, Denize T, Cimadamore A, Wu CJ, Braun D, Einstein D, Catalano PJ, Hammers H. Phase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naive patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B). J Immunother Cancer. 2023 Mar;11(3):e004780. doi: 10.1136/jitc-2022-004780.

  PMID: 36948504 DERIVED

• Atkins MB, Jegede OA, Haas NB, McDermott DF, Bilen MA, Stein M, Sosman JA, Alter R, Plimack ER, Ornstein M, Hurwitz M, Peace DJ, Signoretti S, Denize T, Cimadamore A, Wu CJ, Braun D, Einstein D, Catalano PJ, Hammers H. Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A). J Clin Oncol. 2022 Sep 1;40(25):2913-2923. doi: 10.1200/JCO.21.02938. Epub 2022 Apr 20.

  PMID: 35442713 DERIVED

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Interventions

Nivolumab; Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• Michael B. Atkins, MD

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 17, 2017
• Study Start: April 24, 2017
• Primary Completion: March 25, 2022
• Study Completion: January 23, 2025
• Last Updated: July 10, 2025
• Results First Posted: July 10, 2025

Record last verified: 2025-06

Locations

US (12)