Advanced Renal Cell CarcinomaPhase 2NCT03117309
Study of Front Line Therapy With Nivolumab and Salvage Nivolumab + Ipilimumab in Patients With Advanced Renal Cell Carcinoma
A Phase 2 study testing Nivolumab 240 mg, Ipilimumab 1mg/kg and Nivolumab 3mg/kg in people with Advanced Renal Cell Carcinoma, run by Michael B. Atkins, MD at 12 sites in United States.
Trial summary
Phase II trial of nivolumab in 120 treatment naïve patients with ccRCC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Renal Cell Carcinoma
- What is being tested?
- Nivolumab 240 mg, Ipilimumab 1mg/kg and Nivolumab 3mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 12 sitesUnited States
- Study dates
- 24 Apr 2017to 23 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must meet all of the following applicable inclusion criteria to participate in this study:
- 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.
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- 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
- Hepatic:
- Bilirubin ≤ 1.5× upper limit of normal (ULN); Except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL
- Aspartate aminotransferase (AST) ≤ 3 × ULN
- Alanine aminotransferase (ALT) ≤ 3 × ULN
- Patients should not have received prior systemic therapy for metastatic RCC. Prior radiotherapy must have been completed at least 2 weeks prior to the administration of study drug. Patients must be 2 weeks from prior major surgery and 1 week from pre-treatment biopsy. Prior systemic adjuvant therapy (excluding with PD1 or CTLA4 pathway blockers) is allowed if treatment completed > 12 months previously.
- Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months after the last dose of study drug. NOTE: Contraception is not required for male participants.
- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) during screening for registration purposes. This pregnancy test should be repeated within 24 hours prior to the start of nivolumab. NOTE: "Women of childbearing potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/ml.
- Women must not be breastfeeding.
- Be willing and able to comply with this protocol.
- 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
- Tumor biopsy prior to combination treatment is mandatory. If a 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.
- Must not have had a Grade ≥ 3 irAE on nivolumab monotherapy
- Must not have untreated brain metastases
- Must not have had major surgery or radiation therapy within 14 days of starting study treatment
- Must not have active autoimmune disease
- Must not have a concurrent medical condition requiring use of systemic corticosteroids with prednisone >10 mg per day
- Must not have had prior systemic therapy for Stage IV RCC (except for nivolumab as part of part A of this protocol)
- Prior solid organ or stem cell transplant
Who cannot join
- 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
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- 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)
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Beth Isreal Deaconess Medical Center
Boston, Massachusetts, 02215
Northwestern University Feinberg Schooll Of Medicine
Chicago, Illinois, 60611
University of Illinois Cancer Center
Chicago, Illinois, 60612
Cleveland Clinic
Cleveland, Ohio, 44915
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Yale University, Yale Cancer Center
New Haven, Connecticut, 06520
Columbia University
New York, New York, 10032
Univeristy of Pennsylvania
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Georgetown University
Washington D.C., District of Columbia, 20057
About this study
Official title: Phase II Study of Front Line Therapy With Nivolumab and Salvage Nivolumab + Ipilimumab in Patients With Advanced Renal Cell Carcinoma. HCRN: GU16-260
Phase II trial of nivolumab in 120 treatment naïve patients with ccRCC.
Read the detailed description
Eligible patients with biopsiable (biopsied) disease will receive nivolumab 240 mg IV every 2 weeks x 6 doses then 360 mg every 3 weeks for up to 84 weeks. Tumor response will be assessed at weeks 12, 18 and 24 and then every 12 weeks. For patients who experience RECIST 1.1 defined PD, but remain clinically stable (and asymptomatic), a confirmatory scan after 6 weeks (± 1 week) of additional therapy is suggested. Patients with persistent PD at confirmatory scan will be evaluated for enrollment on Part B of this study. Symptomatic patients may be evaluated for Part B immediately. Patients without confirmed PD can continue on nivolumab therapy.
Patients who experience symptomatic or confirmed PD (or have best response of SD at 12 months) on nivolumab monotherapy will be eligible for consideration for Part B. Part B involves the addition of ipilimumab for up to 4 doses while maintaining nivolumab therapy. Dose of ipilimumab will be 1 mg/kg every 3 weeks together with nivolumab changed to 3 mg/kg every 3 weeks for up to 4 doses. Nivolumab will revert to 360 mg every 3 weeks after the completion of treatment with ipilimumab (beginning week 13-19 of Part B) for up to 48 weeks. Patients will be followed with serial imaging assessments weeks 12, 18 and 24 and then every 12 weeks after the initiation of ipilimumab. The tumor measurements at the time of ipilimumab institution will be the new baseline. If unequivocal symptomatic or confirmed new PD (as defined above) develops, treatment will be discontinued.
Patients for Part B must still meet the eligibility criteria for initial study enrollment. Patients with Grade 3 toxicity on nivolumab monotherapy, serious symptomatic disease that in the opinion of the site investigator requires immediate use of an alternative treatment approach or continued PR/CR will be excluded from enrolling in Part B. It is estimated that roughly half of the patients accrued to the first-line treatment will go on to enroll in Part B.
An additional biopsy will be performed of a metastatic lesion at time of confirmed PD in all patients enrolling in Part B. Confirmation of tumor in the biopsy specimen must occur prior to initiation of treatment on Part B. FFPE and frozen tissue will be stored from this sample and used for correlative studies described below.
An additional cohort of 40 non-ccRCC patients will be enrolled and analyzed separately for evidence of anti-tumor activity (CR, PR and SD and PFS at 1 year of nivolumab). These patients will also be eligible for participation in Part B. We anticipate that the accrual of these 40 patients will be able to be completed within the 1.5 years needed for accrual of the ccRCC patients.
Part A: Nivolumab Administration. Nivolumab will be given every 2 weeks x 6 at a dose of 240 mg Intravenously (IV) and then every 3 weeks at a dose of 360 mg IV until toxicity, complete response, disease progression, SD at 12 months or a maximum of 96 total weeks (12 weeks induction, 84 weeks maintenance) Patients with disease progression (at any time) or SD at 12 months will be eligible to be considered for participation in Part B of the study.
Part B: Nivolumab + Ipilimumab. Patients with Grade 3 toxicity on nivolumab monotherapy, (excluding endocrine toxicity), serious symptomatic disease that in the opinion of the site investigator requires immediate use of an alternative treatment approach or continued PR/CR will be excluded from enrolling in Part B. It is estimated that roughly half of the patients accrued to the first line treatment will go on to enroll in Part B.
Ipilimumab will be given 1 mg/kg every 3 weeks together with nivolumab 240 mg every 3 weeks for up to 4 doses. Nivolumab will revert to 3 mg/kg every 3 weeks after the completion of combination treatment with ipilimumab .
Following the first 4 doses of the combination of nivolumab and ipilimumab, nivolumab monotherapy will again be given every 3 weeks at a dose of 360 mg for a maximum of 48 weeks. Patients may be dosed no less than 18 days from the previous dose of drug; and dosed up to 3 days after the scheduled date, if necessary.
- Conditions
- Advanced Renal Cell Carcinoma
- Being tested
- Nivolumab 240 mg, Ipilimumab 1mg/kg, Nivolumab 3mg/kg, Nivolumab 360mg
- Keywords
- Nivolumab, Ipilimumab, OPDIVO, IgG1 kappa immunoglobulin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab 240 mgDrug
Also called OPDIVO
PART A Nivolumab 240 mg IV every 2 weeks x 6 then initial disease assessment
Ipilimumab 1mg/kgDrug
Also called Yervoy
Ipilimumab 1 mg/kg every 3 weeks x 4
Nivolumab 3mg/kgDrug
Also called OPDIVO
In combination with Ipilimumab
Nivolumab 360mgDrug
Also called OPDIVO
Continue Nivolumab 360 mg IV every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| PART A: Nivolumab | Experimental | Nivolumab 240mg; Nivolumab 360mg Receives: Drug: Nivolumab 240 mg; Drug: Nivolumab 360mg |
| PART B: Nivolumab + Ipilimumab | Experimental | Nivolumab 3mg/kg and Ipilimumab 1mg/kg; Nivolumab 360mg Receives: Drug: Ipilimumab 1mg/kg; Drug: Nivolumab 3mg/kg; Drug: Nivolumab 360mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (5)
Objective Response Rate for ccRCC Patients Treated With Nivolumab Monotherapy
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. ORR = CR +PR Evaluate ORR for nivolumab in patients with treatment naïve clear cell renal cell carcinoma (ccRCC) based on PD-L1 expression.
Measured: Up to 39 Months
Objective Response Rate (ORR) for ccRCC Patients Treated With Nivolumab and Ipilimumab
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. ORR = CR +PR. Evaluate ORR in combined nivolumab and ipilimumab therapy at the time of nivolumab failure for ccRCC patients based on PD-L1 expression.
Measured: Up to 39 Months
Clinical Activity for nccRCC 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. Clinical Activity = CR +PR+SD.
Evaluate the clinical activity of nivolumab in patients with treatment naive nccRCC.
Measured: Up to 39 Months
1-year Progression Free Survival (PFS) Rate for nccRCC 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.
Measured: 1 year
Number of Participants With Adverse Events
Adverse events will be assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Measured: Up to 28 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2017
- Study start24 Apr 2017
- Primary completion25 Mar 2022
- Study completion23 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Renal Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael B. Atkins, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Hoosier Cancer Research Network
- Responsible party
- Sponsor-investigator, Michael B. Atkins, MD, Hoosier Cancer Research Network
- Investigators
- Michael B. Atkins, MD, Study chair, Hoosier Cancer Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03117309
- Sponsor's protocol ID
- HCRN GU16-260
- Status last verified
- Jun 2025
- First submitted
- 10 Apr 2017
- Last updated
- 10 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 36948504Atkins 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.
PubMed 35442713
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Front Line Therapy With Nivolumab and Salvage Nivolumab + Ipilimumab in Patients With Advanced Renal Cell Carcinoma. HCRN: GU16-260
- ClinicalTrials.gov ID
- NCT03117309
- Acronym / sponsor ID
- HCRN GU16-260
- Conditions
- Advanced Renal Cell Carcinoma
- Keywords
- Nivolumab, Ipilimumab, OPDIVO, IgG1 kappa immunoglobulin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Michael B. Atkins, MDUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Hoosier Cancer Research Network
- Study start
- 24 Apr 2017 (actual)
- Primary completion
- 25 Mar 2022 (actual)
- Study completion
- 23 Jan 2025 (actual)
- First posted
- 17 Apr 2017 (actual)
- Results
- Posted 10 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase II trial of nivolumab in 120 treatment naïve patients with ccRCC.
Detailed description
Eligible patients with biopsiable (biopsied) disease will receive nivolumab 240 mg IV every 2 weeks x 6 doses then 360 mg every 3 weeks for up to 84 weeks. Tumor response will be assessed at weeks 12, 18 and 24 and then every 12 weeks. For patients who experience RECIST 1.1 defined PD, but remain clinically stable (and asymptomatic), a confirmatory scan after 6 weeks (± 1 week) of additional therapy is suggested. Patients with persistent PD at confirmatory scan will be evaluated for enrollment on Part B of this study. Symptomatic patients may be evaluated for Part B immediately. Patients without confirmed PD can continue on nivolumab therapy.
Patients who experience symptomatic or confirmed PD (or have best response of SD at 12 months) on nivolumab monotherapy will be eligible for consideration for Part B. Part B involves the addition of ipilimumab for up to 4 doses while maintaining nivolumab therapy. Dose of ipilimumab will be 1 mg/kg every 3 weeks together with nivolumab changed to 3 mg/kg every 3 weeks for up to 4 doses. Nivolumab will revert to 360 mg every 3 weeks after the completion of treatment with ipilimumab (beginning week 13-19 of Part B) for up to 48 weeks. Patients will be followed with serial imaging assessments weeks 12, 18 and 24 and then every 12 weeks after the initiation of ipilimumab. The tumor measurements at the time of ipilimumab institution will be the new baseline. If unequivocal symptomatic or confirmed new PD (as defined above) develops, treatment will be discontinued.
Patients for Part B must still meet the eligibility criteria for initial study enrollment. Patients with Grade 3 toxicity on nivolumab monotherapy, serious symptomatic disease that in the opinion of the site investigator requires immediate use of an alternative treatment approach or continued PR/CR will be excluded from enrolling in Part B. It is estimated that roughly half of the patients accrued to the first-line treatment will go on to enroll in Part B.
An additional biopsy will be performed of a metastatic lesion at time of confirmed PD in all patients enrolling in Part B. Confirmation of tumor in the biopsy specimen must occur prior to initiation of treatment on Part B. FFPE and frozen tissue will be stored from this sample and used for correlative studies described below.
An additional cohort of 40 non-ccRCC patients will be enrolled and analyzed separately for evidence of anti-tumor activity (CR, PR and SD and PFS at 1 year of nivolumab). These patients will also be eligible for participation in Part B. We anticipate that the accrual of these 40 patients will be able to be completed within the 1.5 years needed for accrual of the ccRCC patients.
Part A: Nivolumab Administration. Nivolumab will be given every 2 weeks x 6 at a dose of 240 mg Intravenously (IV) and then every 3 weeks at a dose of 360 mg IV until toxicity, complete response, disease progression, SD at 12 months or a maximum of 96 total weeks (12 weeks induction, 84 weeks maintenance) Patients with disease progression (at any time) or SD at 12 months will be eligible to be considered for participation in Part B of the study.
Part B: Nivolumab + Ipilimumab. Patients with Grade 3 toxicity on nivolumab monotherapy, (excluding endocrine toxicity), serious symptomatic disease that in the opinion of the site investigator requires immediate use of an alternative treatment approach or continued PR/CR will be excluded from enrolling in Part B. It is estimated that roughly half of the patients accrued to the first line treatment will go on to enroll in Part B.
Ipilimumab will be given 1 mg/kg every 3 weeks together with nivolumab 240 mg every 3 weeks for up to 4 doses. Nivolumab will revert to 3 mg/kg every 3 weeks after the completion of combination treatment with ipilimumab .
Following the first 4 doses of the combination of nivolumab and ipilimumab, nivolumab monotherapy will again be given every 3 weeks at a dose of 360 mg for a maximum of 48 weeks. Patients may be dosed no less than 18 days from the previous dose of drug; and dosed up to 3 days after the scheduled date, if necessary.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PART A: Nivolumab | Experimental | Drug: Nivolumab 240 mg, Drug: Nivolumab 360mgNivolumab 240mg; Nivolumab 360mg |
| PART B: Nivolumab + Ipilimumab | Experimental | Drug: Ipilimumab 1mg/kg, Drug: Nivolumab 3mg/kg, Drug: Nivolumab 360mgNivolumab 3mg/kg and Ipilimumab 1mg/kg; Nivolumab 360mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Subject must meet all of the following applicable inclusion criteria to participate in this study:
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab 240 mgAlso: OPDIVOPART A Nivolumab 240 mg IV every 2 weeks x 6 then initial disease assessment | Drug | PART A: Nivolumab |
| Ipilimumab 1mg/kgAlso: YervoyIpilimumab 1 mg/kg every 3 weeks x 4 | Drug | PART B: Nivolumab + Ipilimumab |
| Nivolumab 3mg/kgAlso: OPDIVOIn combination with Ipilimumab | Drug | PART B: Nivolumab + Ipilimumab |
| Nivolumab 360mgAlso: OPDIVOContinue Nivolumab 360 mg IV every 3 weeks | Drug | PART A: Nivolumab, PART B: Nivolumab + Ipilimumab |
Primary outcome
1-year Progression Free Survival (PFS) Rate for ccRCC Patients
Time frame: 1 year
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.
5 secondary outcomes
Objective Response Rate for ccRCC Patients Treated With Nivolumab Monotherapy
Time frame: Up to 39 Months
Objective Response Rate (ORR) for ccRCC Patients Treated With Nivolumab and Ipilimumab
Time frame: Up to 39 Months
Clinical Activity for nccRCC Patients
Time frame: Up to 39 Months
1-year Progression Free Survival (PFS) Rate for nccRCC Patients
Time frame: 1 year
Number of Participants With Adverse Events
Time frame: Up to 28 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36948504Atkins 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.
- Derived from this study: PubMed 35442713Atkins 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.
- Hoosier Cancer Research Network WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael B. Atkins, MD study chair
Hoosier Cancer Research Network
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab 240 mg, Ipilimumab 1mg/kg and Nivolumab 3mg/kg in people with Advanced Renal Cell Carcinoma, run by Michael B. Atkins, MD at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-year Progression Free Survival (PFS) Rate for ccRCC Patients (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03117309, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2025.