Study of Front Line Therapy With Nivolumab and Salvage Nivolumab + Ipilimumab in Patients With Advanced Renal Cell Carcinoma
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|ClinicalTrials.gov Identifier: NCT03117309|
Recruitment Status : Active, not recruiting
First Posted : April 17, 2017
Last Update Posted : October 26, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Advanced Renal Cell Carcinoma||Drug: Nivolumab 240 mg Drug: Ipilimumab 1mg/kg Drug: Nivolumab 3mg/kg Drug: Nivolumab 360mg||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||164 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Masking Description:||Open Label|
|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|
|Actual Study Start Date :||April 24, 2017|
|Actual Primary Completion Date :||March 25, 2022|
|Estimated Study Completion Date :||September 2023|
Experimental: PART A: Nivolumab
Nivolumab 240mg; Nivolumab 360mg
Drug: Nivolumab 240 mg
PART A Nivolumab 240 mg IV every 2 weeks x 6 then initial disease assessment
Other Name: OPDIVO
Drug: Nivolumab 360mg
Continue Nivolumab 360 mg IV every 3 weeks
Other Name: OPDIVO
Experimental: PART B: Nivolumab + Ipilimumab
Nivolumab 3mg/kg and Ipilimumab 1mg/kg; Nivolumab 360mg
Drug: Ipilimumab 1mg/kg
Ipilimumab 1 mg/kg every 3 weeks x 4
Other Name: Yervoy
Drug: Nivolumab 3mg/kg
In combination with Ipilimumab
Other Name: OPDIVO
Drug: Nivolumab 360mg
Continue Nivolumab 360 mg IV every 3 weeks
Other Name: OPDIVO
- Progression Free Survival (PFS) rate [ Time Frame: 1 year ]Determine the PFS rate at 1 year of nivolumab in patients with treatment naïve ccRCC based on tumor PD-L1 expression
- Progression Free Survival (PFS) rate [ Time Frame: 1 year ]Determine the PFS at 1 year of nivolumab in patients with treatment naïve ccRCC based on the PD1- Blockade Durable Response Predictive (PRP) biomarker model developed in the DFHCC Kidney Cancer SPORE
- Objective Response Rate (CR/PR) [ Time Frame: 1 year ]Determine the objective response rate (CR/PR) for nivolumab in patients with treatment naïve ccRCC
- Response Rate [ Time Frame: 1 year ]Determine the response rate of combined nivolumab and ipilimumab therapy at the time of nivolumab failure
- Clinical Activity (Complete Response (CR), Partial Response (PR) and Stable Disease (SD) [ Time Frame: 1 year ]Determine the clinical activity (CR, PR and SD) at 1 year of nivolumab in patients with treatment naive nccRCC
- Progression Free Survival (PFS) at one year [ Time Frame: 1 year ]Evaluate patients on nivolumab for progressive disease or death
- Toxicity by calculating the frequency and percentage of adverse event terms (CTCAE v4) [ Time Frame: 1 year ]Assess the toxicity of nivolumab monotherapy in patients with treatment naïve cc or nccRCC by calculating the frequency and percentage of adverse event terms (CTCAE v4)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Inclusion Criteria-Part A:
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.
- 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:
- 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)
- 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
- 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.
- 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)
Inclusion/Exclusion Criteria- Part B
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03117309
|United States, Connecticut|
|Yale University, Yale Cancer Center|
|New Haven, Connecticut, United States, 06520|
|United States, District of Columbia|
|Washington, District of Columbia, United States, 20057|
|United States, Georgia|
|Winship Cancer Institute of Emory University|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|Northwestern University Feinberg Schooll Of Medicine|
|Chicago, Illinois, United States, 60611|
|University of Illinois Cancer Center|
|Chicago, Illinois, United States, 60612|
|United States, Massachusetts|
|Beth Isreal Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|United States, New Jersey|
|Hackensack University Medical Center|
|Hackensack, New Jersey, United States, 07601|
|United States, New York|
|New York, New York, United States, 10032|
|United States, Ohio|
|Cleveland, Ohio, United States, 44915|
|United States, Pennsylvania|
|Univeristy of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111|
|United States, Texas|
|University of Texas Southwestern Medical Center|
|Dallas, Texas, United States, 75390|
|Study Chair:||Michael B. Atkins, MD||Hoosier Cancer Research Network|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Michael B. Atkins, MD, Sponsor-Investigator, Hoosier Cancer Research Network|
|Other Study ID Numbers:||
|First Posted:||April 17, 2017 Key Record Dates|
|Last Update Posted:||October 26, 2022|
|Last Verified:||October 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||Yes|
IgG1 kappa immunoglobulin
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action